Natural gas

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The global Natural Gas Trade in 2013, numbers are in billion cubic meters per year. As can be seen a large amount of Gas trade is going through the sea now. Qatar exports more than half as much gas as Russia through their sea network without any pipelines.^[1]

Natural gas extraction by countries in cubic meters per year.

Natural gas is a fossil fuel formed when layers of buried plants, gases, and animals are exposed to intense heat and pressure over thousands of years. The energy that the plants originally obtained from the sun is stored in the form of chemical bonds in natural gas. Natural gas is a nonrenewable resource because it cannot be replenished on a human time frame.^[2] Natural gas is a hydrocarbon gas mixture consisting primarily of methane, but commonly includes varying amounts of other higher alkanes and sometimes a usually lesser percentage of carbon dioxide, nitrogen, and/or hydrogen sulfide.^[3] Natural gas is an energy source often used for heating, cooking, and electricity generation. It is also used as fuel for vehicles and as a chemical feedstock in the manufacture of plastics and other commercially important organic chemicals.

Natural gas is found in deep underground rock formations or associated with other hydrocarbon reservoirs in coal beds and as methane clathrates. Petroleum is another resource and fossil fuel found in close proximity to, and with natural gas. Most natural gas was created over time by two mechanisms: biogenic and thermogenic. Biogenic gas is created by methanogenic organisms in marshes, bogs, landfills, and shallow sediments. Deeper in the earth, at greater temperature and pressure, thermogenic gas is created from buried organic material.^[4][5]

Before natural gas can be used as a fuel, it must be processed to remove impurities, including water, to meet the specifications of marketable natural gas. The by-products of this processing include: ethane, propane, butanes, pentanes, and higher molecular weight hydrocarbons, hydrogen sulfide (which may be converted into pure sulfur), carbon dioxide, water vapor, and sometimes helium and nitrogen.

Natural gas is often informally referred to simply as "gas", especially when compared to other energy sources such as oil or coal. However, it is not to be confused with gasoline, especially in North America, where the term gasoline is often shortened in colloquial usage to gas.

Natural gas was used by the Chinese in about 500 BC. They discovered a way to transport gas seeping from the ground in crude pipelines of bamboo to where it was used to boil sea water to extract the salt.^[6] The world's first industrial extraction of natural gas started at Fredonia, New York, USA in 1825.^[7] By 2009, 66 trillion cubic meters (or 8%) had been used out of the total 850 trillion cubic meters of estimated remaining recoverable reserves of natural gas.^[8] Based on an estimated 2015 world consumption rate of about 3.4 trillion cubic meters of gas per year, the total estimated remaining economically recoverable reserves of natural gas would last 250 years at current consumption rates. An annual increase in usage of 2-3% could result in currently recoverable reserves lasting significantly less, perhaps as few as 80 to 100 years.^[8]

Natural gas coming out of the ground, Taiwan.

Sources

Natural gas

Natural gas drilling rig in Texas.

Trends in the top five natural gas-producing countries (US EIA data)

In the 19th century, natural gas was usually obtained as a by-product of producing oil, since the small, light gas carbon chains came out of solution as the extracted fluids underwent pressure reduction from the reservoir to the surface, similar to uncapping a soft drink bottle where the carbon dioxide effervesces. Unwanted natural gas was a disposal problem in the active oil fields. If there was not a market for natural gas near the wellhead it was virtually valueless since it had to be piped to the end user.

In the 19th century and early 20th century, such unwanted gas was usually burned off at oil fields. Today, unwanted gas (or stranded gas without a market) associated with oil extraction often is returned to the reservoir with 'injection' wells while awaiting a possible future market or to repressurize the formation, which can enhance extraction rates from other wells. In regions with a high natural gas demand (such as the US), pipelines are constructed when it is economically feasible to transport gas from a wellsite to an end consumer.

In addition to transporting gas via pipelines for use in power generation, other end uses for natural gas include export as liquefied natural gas (LNG) or conversion of natural gas into other liquid products via gas-to-liquids (GTL) technologies. GTL technologies can convert natural gas into liquids products such as gasoline, diesel or jet fuel. A variety of GTL technologies have been developed, including Fischer-Tropsch (F-T), methanol to gasoline (MTG) and STG+. F-T produces a synthetic crude that can be further refined into finished products, while MTG can produce synthetic gasoline from natural gas. STG+ can produce drop-in gasoline, diesel, jet fuel and aromatic chemicals directly from natural gas via a single-loop process.^[9] In 2011, Royal Dutch Shell’s 140,000 barrel per day F-T plant went into operation in Qatar.

Natural gas can be "associated" (found in oil fields), or "non-associated" (isolated in natural gas fields), and is also found in coal beds (as coalbed methane).^[10] It sometimes contains a significant amount of ethane, propane, butane, and pentane—heavier hydrocarbons removed for commercial use prior to the methane being sold as a consumer fuel or chemical plant feedstock. Non-hydrocarbons such as carbon dioxide, nitrogen, helium (rarely), and hydrogen sulfide must also be removed before the natural gas can be transported.^[11]

Natural gas extracted from oil wells is called casinghead gas (whether or not truly produced up the annulus and through a casinghead outlet) or associated gas. The natural gas industry is extracting an increasing quantity of gas from challenging resource types: sour gas, tight gas, shale gas, and coalbed methane.

There is some disagreement on which country has the largest proven gas reserves. Sources that consider that Russia has by far the largest proven reserves include the US CIA (47.6 trillion cubic meters),^[12] the US Energy Information Administration (47.8 tcm),^[13] and OPEC (48.7 tcm).^[14] However, BP credits Russia with only 32.9 tcm,^[15] which would place it in second place, slightly behind Iran (33.1 to 33.8 tcm, depending on the source). With Gazprom, Russia is frequently the world's largest natural gas extractor. Major proven resources (in billion cubic meters) are world 187,300 (2013), Iran 33,600 (2013), Russia 32,900 (2013), Qatar 25,100 (2013), Turkmenistan 17,500 (2013) and the United States 8,500 (2013).

It is estimated that there are about 900 trillion cubic meters of "unconventional" gas such as shale gas, of which 180 trillion may be recoverable.^[16] In turn, many studies from MIT, Black & Veatch and the DOE predict that natural gas will account for a larger portion of electricity generation and heat in the future.^[17]

The world's largest gas field is the offshore South Pars / North Dome Gas-Condensate field, shared between Iran and Qatar. It is estimated to have 51 trillion cubic meters of natural gas and 50 billion barrels of natural gas condensates.

Because natural gas is not a pure product, as the reservoir pressure drops when non-associated gas is extracted from a field under supercritical (pressure/temperature) conditions, the higher molecular weight components may partially condense upon isothermic depressurizing—an effect called retrograde condensation. The liquid thus formed may get trapped as the pores of the gas reservoir get depleted. One method to deal with this problem is to re-inject dried gas free of condensate to maintain the underground pressure and to allow re-evaporation and extraction of condensates. More frequently, the liquid condenses at the surface, and one of the tasks of the gas plant is to collect this condensate. The resulting liquid is called natural gas liquid (NGL) and has commercial value.

Shale gas

The location of shale gas compared to other types of gas deposits.

Shale gas is natural gas produced from shale. Because shale has matrix permeability too low to allow gas to flow in economical quantities, shale gas wells depend on fractures to allow the gas to flow. Early shale gas wells depended on natural fractures through which gas flowed; almost all shale gas wells today require fractures artificially created by hydraulic fracturing. Since 2000, shale gas has become a major source of natural gas in the United States and Canada.^[18] Following the success in the United States, shale gas exploration is beginning in countries such as Poland, China, and South Africa.^[19][20][21] With the increase of shale production it has caused the United States to become the number one natural gas producer in the world^[22]

Town gas

Town gas is a flammable gaseous fuel made by the destructive distillation of coal and contains a variety of calorific gases including hydrogen, carbon monoxide, methane, and other volatile hydrocarbons, together with small quantities of non-calorific gases such as carbon dioxide and nitrogen, and is used in a similar way to natural gas. This is a historical technology, not usually economically competitive with other sources of fuel gas today. But there are still some specific cases where it is the best option and it may be so into the future.
Most town "gashouses" located in the eastern US in the late 19th and early 20th centuries were simple by-product coke ovens that heated bituminous coal in air-tight chambers. The gas driven off from the coal was collected and distributed through networks of pipes to residences and other buildings where it was used for cooking and lighting. (Gas heating did not come into widespread use until the last half of the 20th century.) The coal tar (or asphalt) that collected in the bottoms of the gashouse ovens was often used for roofing and other waterproofing purposes, and when mixed with sand and gravel was used for paving streets.

Biogas

Methanogenic archaea are responsible for all biological sources of methane. Some live in symbiotic relationships with other life forms, including termites, ruminants, and cultivated crops. Other sources of methane, the principal component of natural gas, include landfill gas, biogas, and methane hydrate. When methane-rich gases are produced by the anaerobic decay of non-fossil organic matter (biomass), these are referred to as biogas (or natural biogas). 

Sources of biogas include swamps, marshes, and landfills (see landfill gas), as well as agricultural waste materials such as sewage sludge and manure^[23] by way of anaerobic digesters, in addition to enteric fermentation, particularly in cattle. Landfill gas is created by decomposition of waste in landfill sites. Excluding water vapor, about half of landfill gas is methane and most of the rest is carbon dioxide, with small amounts of nitrogen, oxygen, and hydrogen, and variable trace amounts of hydrogen sulfide and siloxanes. If the gas is not removed, the pressure may get so high that it works its way to the surface, causing damage to the landfill structure, unpleasant odor, vegetation die-off, and an explosion hazard. The gas can be vented to the atmosphere, flared or burned to produce electricity or heat. Biogas can also be produced by separating organic materials from waste that otherwise goes to landfills. This method is more efficient than just capturing the landfill gas it produces. Anaerobic lagoons produce biogas from manure, while biogas reactors can be used for manure or plant parts. Like landfill gas, biogas is mostly methane and carbon dioxide, with small amounts of nitrogen, oxygen and hydrogen. However, with the exception of pesticides, there are usually lower levels of contaminants.
Landfill gas cannot be distributed through utility natural gas pipelines unless it is cleaned up to less than 3 per cent CO₂, and a few parts per million H
2S, because CO₂ and H
2S corrode the pipelines.^[24] The presence of CO₂ will lower the energy level of the gas below requirements for the pipeline.^{[clarification needed]} Siloxanes in the gas will form deposits in gas burners and need to be removed prior to entry into any gas distribution or transmission system. Consequently it may be more economical to burn the gas on site or within a short distance of the landfill using a dedicated pipeline. Water vapor is often removed, even if the gas is burned on site. If low temperatures condense water out of the gas, siloxanes can be lowered as well because they tend to condense out with the water vapor. Other non-methane components may also be removed to meet emission standards, to prevent fouling of the equipment or for environmental considerations. Co-firing landfill gas with natural gas improves combustion, which lowers emissions.

Biogas, and especially landfill gas, are already used in some areas, but their use could be greatly expanded. Experimental systems were being proposed^[when?] for use in parts of Hertfordshire, UK, and Lyon in France.^{[citation needed]} Using materials that would otherwise generate no income, or even cost money to get rid of, improves the profitability and energy balance of biogas production. Gas generated in sewage treatment plants is commonly used to generate electricity. For example, the Hyperion sewage plant in Los Angeles burns 8 million cubic feet (230,000 m³) of gas per day to generate power^[25] New York City utilizes gas to run equipment in the sewage plants, to generate electricity, and in boilers.^[26] Using sewage gas to make electricity is not limited to large cities. The city of Bakersfield, California, uses cogeneration at its sewer plants.^[27] California has 242 sewage wastewater treatment plants, 74 of which have installed anaerobic digesters. The total biopower generation from the 74 plants is about 66 MW.^[28]

The McMahon natural gas processing plant in Taylor, British Columbia, Canada.^[29]

Crystallized natural gas — hydrates

Huge quantities of natural gas (primarily methane) exist in the form of hydrates under sediment on offshore continental shelves and on land in arctic regions that experience permafrost, such as those in Siberia. Hydrates require a combination of high pressure and low temperature to form.

In 2010, the cost of extracting natural gas from crystallized natural gas was estimated to 100–200 per cent the cost of extracting natural gas from conventional sources, and even higher from offshore deposits.^[30]

In 2013, Japan Oil, Gas and Metals National Corporation (JOGMEC) announced that they had recovered commercially relevant quantities of natural gas from methane hydrate.^[31]

Natural gas processing

The image below is a schematic block flow diagram of a typical natural gas processing plant. It shows the various unit processes used to convert raw natural gas into sales gas pipelined to the end user markets.
The block flow diagram also shows how processing of the raw natural gas yields byproduct sulfur, byproduct ethane, and natural gas liquids (NGL) propane, butanes and natural gasoline (denoted as pentanes +).^{[32][33][34][35][36]}

Schematic flow diagram of a typical natural gas processing plant.

Depletion

Uses

Mid Stream Natural Gas

Natural gas flowing in the distribution lines and at the natural gas well head are often used to power natural gas powered engines. These engines rotate compressors to facilitate the natural gas transmission. These compressors are required in the mid-stream line to pressurize and to re-pressurize the natural gas in the transmission line as the gas travels. The natural gas transmission lines extend to the natural gas processing plant or unit which removes the higher molecular weighted natural gas hydrocarbons to produce a British thermal unit (BTU) value between 950 and 1050 BTUs. The processed natural gas may then be used for residential, commercial and industrial uses.
Often mid-stream and well head gases require removal of many of the various hydrocarbon species contained within the natural gas. Some of these gases include heptane, pentane, propane and other hydrocarbons with molecular weights above Methane (CH4) to produce a natural gas fuel which is used to operate the natural gas engines for further pressurized transmission. Typically, natural gas compressors require 950 to 1050 BTU per cubic foot to operate at the natural gas engines rotational name plate specifications.

Several methods are used to remove these higher molecular weighted gases for use at the natural gas engine. A few technologies are as follows:

• Joule–Thomson Skid
• Cryogenic or Chiller system
• Chemical Enzymology system^[37]

Power generation

Natural gas is a major source of electricity generation through the use of cogeneration, gas turbines and steam turbines. Natural gas is also well suited for a combined use in association with renewable energy sources such as wind or solar^[38] and for alimenting peak-load power stations functioning in tandem with hydroelectric plants. Most grid peaking power plants and some off-grid engine-generators use natural gas. Particularly high efficiencies can be achieved through combining gas turbines with a steam turbine in combined cycle mode. Natural gas burns more cleanly than other hydrocarbon fuels, such as oil and coal, and produces less carbon dioxide per unit of energy released. For an equivalent amount of heat, burning natural gas produces about 30 per cent less carbon dioxide than burning petroleum and about 45 per cent less than burning coal.^[39] The Energy Information Administration reports the following emissions in million metric tons of carbon dioxide in the world:

• Natural gas: 6,799
• Petroleum: 11,695
• Coal: 13,787

For 2012 as the official energy statistics of the US Government.^[40]

Coal-fired electric power generation emits around 2,000 pounds of carbon dioxide for every megawatt hour generated, which is almost double the carbon dioxide released by a natural gas-fired electric plant per megawatt hour generated. Because of this higher carbon efficiency of natural gas generation, as the fuel mix in the United States has changed to reduce coal and increase natural gas generation, carbon dioxide emissions have unexpectedly fallen. Those measured in the first quarter of 2012 were the lowest of any recorded for the first quarter of any year since 1992.^[41]

Combined cycle power generation using natural gas is currently the cleanest available source of power using hydrocarbon fuels, and this technology is widely and increasingly used as natural gas can be obtained at increasingly reasonable costs. Fuel cell technology may eventually provide cleaner options for converting natural gas into electricity, but as yet it is not price-competitive. Locally produced electricity and heat using natural gas powered Combined Heat and Power plant (CHP or Cogeneration plant) is considered energy efficient and a rapid way to cut carbon emissions.^[42]

Domestic use

Natural gas dispensed from a simple stovetop can generate temperatures in excess of 1100 °C (2000 °F) making it a powerful domestic cooking and heating fuel.^[43] In much of the developed world it is supplied through pipes to homes, where it is used for many purposes including ranges and ovens, gas-heated clothes dryers, heating/cooling, and central heating. Heaters in homes and other buildings may include boilers, furnaces, and water heaters.
Compressed natural gas (CNG) is used in rural homes without connections to piped-in public utility services, or with portable grills.^{[citation needed]} Natural gas is also supplied by independent natural gas suppliers through Natural Gas Choice programs throughout the United States. However, as CNG costs more than LPG, LPG (propane) is the dominant source of rural gas.

A Washington, D.C. Metrobus, which runs on natural gas.

Transportation

CNG is a cleaner alternative to other automobile fuels such as gasoline (petrol) and diesel. By the end of 2012 there were 17.25 million natural gas vehicles worldwide, led by Iran (3.3 million), Pakistan (3.1 million), Argentina (2.18 million), Brazil (1.73 million), India (1.5 million), and China (1.5 million).^[44] The energy efficiency is generally equal to that of gasoline engines, but lower compared with modern diesel engines. Gasoline/petrol vehicles converted to run on natural gas suffer because of the low compression ratio of their engines, resulting in a cropping of delivered power while running on natural gas (10%–15%). CNG-specific engines, however, use a higher compression ratio due to this fuel's higher octane number of 120–130.^{[45] [46]}

Fertilizers

Natural gas is a major feedstock for the production of ammonia, via the Haber process, for use in fertilizer production.

Aviation

Russian aircraft manufacturer Tupolev is currently running a development program to produce LNG- and hydrogen-powered aircraft.^[47] The program has been running since the mid-1970s, and seeks to develop LNG and hydrogen variants of the Tu-204 and Tu-334 passenger aircraft, and also the Tu-330 cargo aircraft. It claims that at current market prices, an LNG-powered aircraft would cost 5,000 roubles (~ US$218/ £112) less to operate per ton, roughly equivalent to 60 per cent, with considerable reductions to carbon monoxide, hydrocarbon and nitrogen oxide emissions.

The advantages of liquid methane as a jet engine fuel are that it has more specific energy than the standard kerosene mixes do and that its low temperature can help cool the air which the engine compresses for greater volumetric efficiency, in effect replacing an intercooler. Alternatively, it can be used to lower the temperature of the exhaust.

Hydrogen

Natural gas can be used to produce hydrogen, with one common method being the hydrogen reformer. Hydrogen has many applications: it is a primary feedstock for the chemical industry, a hydrogenating agent, an important commodity for oil refineries, and the fuel source in hydrogen vehicles.

Other

Natural gas is also used in the manufacture of fabrics, glass, steel, plastics, paint, and other products.^{[citation needed]}

Storage and transport

Polyethylene plastic main being placed in a trench.

Because of its low density, it is not easy to store natural gas or to transport it by vehicle. Natural gas pipelines are impractical across oceans. Many existing pipelines in America are close to reaching their capacity, prompting some politicians representing northern states to speak of potential shortages. In Western Europe, the gas pipeline network is already dense.^[48] New pipelines are planned or under construction in Eastern Europe and between gas fields in Russia, Near East and Northern Africa and Western Europe. See also List of natural gas pipelines.

LNG carriers transport liquefied natural gas (LNG) across oceans, while tank trucks can carry liquefied or compressed natural gas (CNG) over shorter distances. Sea transport using CNG carrier ships that are now under development may be competitive with LNG transport in specific conditions.

Gas is turned into liquid at a liquefaction plant, and is returned to gas form at regasification plant at the terminal. Shipborne regasification equipment is also used. LNG is the preferred form for long distance, high volume transportation of natural gas, whereas pipeline is preferred for transport for distances up to 4,000 km (2,485 mi) over land and approximately half that distance offshore.

CNG is transported at high pressure, typically above 200 bars. Compressors and decompression equipment are less capital intensive and may be economical in smaller unit sizes than liquefaction/regasification plants. Natural gas trucks and carriers may transport natural gas directly to end-users, or to distribution points such as pipelines.

Peoples Gas Manlove Field natural gas storage area in Newcomb Township, Champaign County, Illinois. In the foreground (left) is one of the numerous wells for the underground storage area, with an LNG plant, and above ground storage tanks are in the background (right).

In the past, the natural gas which was recovered in the course of recovering petroleum could not be profitably sold, and was simply burned at the oil field in a process known as flaring. Flaring is now illegal in many countries.^[49] Additionally, higher demand in the last 20–30 years has made production of gas associated with oil economically viable. As a further option, the gas is now sometimes re-injected into the formation for enhanced oil recovery by pressure maintenance as well as miscible or immiscible flooding. Conservation, re-injection, or flaring of natural gas associated with oil is primarily dependent on proximity to markets (pipelines), and regulatory restrictions.

A "master gas system" was invented in Saudi Arabia in the late 1970s, ending any necessity for flaring. Satellite observation, however, shows that flaring^[50] and venting^[51] are still practiced in some gas-extracting countries.

Natural gas is used to generate electricity and heat for desalination. Similarly, some landfills that also discharge methane gases have been set up to capture the methane and generate electricity.

Natural gas is often stored underground inside depleted gas reservoirs from previous gas wells, salt domes, or in tanks as liquefied natural gas. The gas is injected in a time of low demand and extracted when demand picks up. Storage nearby end users helps to meet volatile demands, but such storage may not always be practicable.

With 15 countries accounting for 84 per cent of the worldwide extraction, access to natural gas has become an important issue in international politics, and countries vie for control of pipelines.^[52] In the first decade of the 21st century, Gazprom, the state-owned energy company in Russia, engaged in disputes with Ukraine and Belarus over the price of natural gas, which have created concerns that gas deliveries to parts of Europe could be cut off for political reasons.^[53] The United States is preparing to export natural gas.^[54]

Floating Liquefied Natural Gas (FLNG) is an innovative technology designed to enable the development of offshore gas resources that would otherwise remain untapped because due to environmental or economic factors it is nonviable to develop them via a land-based LNG operation. FLNG technology also provides a number of environmental and economic advantages:

• Environmental – Because all processing is done at the gas field, there is no requirement for long pipelines to shore, compression units to pump the gas to shore, dredging and jetty construction, and onshore construction of an LNG processing plant, which significantly reduces the environmental footprint.^[55] Avoiding construction also helps preserve marine and coastal environments. In addition, environmental disturbance will be minimised during decommissioning because the facility can easily be disconnected and removed before being refurbished and re-deployed elsewhere.

• Economic – Where pumping gas to shore can be prohibitively expensive, FLNG makes development economically viable. As a result, it will open up new business opportunities for countries to develop offshore gas fields that would otherwise remain stranded, such as those offshore East Africa.^[56]

Many gas and oil companies are considering the economic and environmental benefits of Floating Liquefied Natural Gas (FLNG). However, for the time being, the only FLNG facility now in development is being built by Shell,^[57] due for completion around 2017.^[58]

Environmental effects

Effect of natural gas release

Natural gas is mainly composed of methane. After release to the atmosphere it is removed over about 10 years by gradual oxidation to carbon dioxide and water by hydroxyl radicals (·OH) formed in the troposphere or stratosphere, giving the overall chemical reaction CH₄ + 2O₂→ CO₂ + 2H₂O.^[59][60] While the lifetime of atmospheric methane is relatively short when compared to carbon dioxide,^[61] it is more efficient at trapping heat in the atmosphere, so that a given quantity of methane has 84 times the global-warming potential of carbon dioxide over a 20-year period and 28 times over a 100-year period. Natural gas is thus a more potent greenhouse gas than carbon dioxide due to the greater global-warming potential of methane.^[62] Current estimates by the EPA place global emissions of methane at 85 billion cubic metres (3.0×10^¹² cu ft) annually,^[61] or 3.2 per cent of global production.^[63] Direct emissions of methane represented 14.3 per cent of all global anthropogenic greenhouse gas emissions in 2004.^[64]
During extraction, storage, transportation, and distribution, natural gas is known to leak into the atmosphere, particularly during the extraction process. A Cornell University study in 2011 demonstrated that the leak rate of methane may be high enough to jeopardize its global warming advantage over coal.^[65] This study was criticized later for its high assumption of methane leakage values.^[66] These values were later shown to be close to the findings of the Scientists at the National Oceanic and Atmospheric Administration.^[67] Natural gas extraction also releases an isotope of Radon, ranging from 5 to 200,000 Becquerels per cubic meter.^[68]

CO₂ emissions

Natural gas is often described as the cleanest fossil fuel. It produces about 29% and 44% less carbon dioxide per joule delivered than oil and coal respectively,^[39] and potentially fewer pollutants than other hydrocarbon fuels.^[69] However, in absolute terms, it comprises a substantial percentage of human carbon emissions, and this contribution is projected to grow. According to the IPCC Fourth Assessment Report, in 2004, natural gas produced about 5.3 billion tons a year of CO₂ emissions, while coal and oil produced 10.6 and 10.2 billion tons respectively. According to an updated version of the Special Report on Emissions Scenario by 2030, natural gas would be the source of 11 billion tons a year, with coal and oil now 8.4 and 17.2 billion respectively because demand is increasing 1.9 percent a year.

Other pollutants

Natural gas produces far lower amounts of sulfur dioxide and nitrous oxides than any other hydrocarbon fuels.^[70] The other pollutants due to natural gas combustion are listed below^[69][71] in parts per million (ppm):

• Carbon monoxide - 40 ppm
• Sulfur dioxide - 1 ppm
• Nitrogen oxide - 92 ppm
• Particulates - 7 ppm

Safety concerns

A pipeline odorant injection station

Production

In mines, where methane seeping from rock formations has no odor, sensors are used, and mining apparatus such as the Davy lamp has been specifically developed to avoid ignition sources.

Some gas fields yield sour gas containing hydrogen sulfide (H₂S). This untreated gas is toxic. Amine gas treating, an industrial scale process which removes acidic gaseous components, is often used to remove hydrogen sulfide from natural gas.^[72]

Extraction of natural gas (or oil) leads to decrease in pressure in the reservoir. Such decrease in pressure in turn may result in subsidence, sinking of the ground above. Subsidence may affect ecosystems, waterways, sewer and water supply systems, foundations, and so on.

Another ecosystem effect results from the noise of the process. This can change the composition of animal life in the area, and have consequences for plants as well in that animals disperse seeds and pollen.^{[citation needed]}

Releasing the gas from low-permeability reservoirs is accomplished by a process called hydraulic fracturing or "hydrofracking". To allow the natural gas to flow out of the shale, oil operators force 1 to 9 million US gallons (34,000 m³) of water mixed with a variety of chemicals through the wellbore casing into the shale. The high pressure water breaks up or "fracks" the shale, which releases the trapped gas. Sand is added to the water as a proppant to keep the fractures in the shale open, thus enabling the gas to flow into the casing and then to the surface. The chemicals are added to the frack fluid to reduce friction and combat corrosion. During the extracting life of a gas well, other low concentrations of other chemical substances may be used, such as biocides to eliminate fouling, scale and corrosion inhibitors, oxygen scavengers to remove a source of corrosion, and acids to clean the perforations in the pipe.

Dealing with fracking fluid can be a challenge. Along with the gas, 30 percent to 70 percent of the chemically laced frack fluid, or flow back, returns to the surface. Additionally, a significant amount of brine, containing salts and other minerals, may be produced with the gas.

Use

In order to assist in detecting leaks, a minute amount of odorant is added to the otherwise colorless and almost odorless gas used by consumers. The odor has been compared to the smell of rotten eggs, due to the added tert-Butylthiol (t-butyl mercaptan). Sometimes a related compound, thiophane, may be used in the mixture. Situations in which an odorant that is added to natural gas can be detected by analytical instrumentation, but cannot be properly detected by an observer with a normal sense of smell, have occurred in the natural gas industry. This is caused by odor masking, when one odorant overpowers the sensation of another. As of 2011, the industry is conducting research on the causes of odor masking.^[73]

Gas network emergency vehicle responding to a major fire in Kiev, Ukraine

Explosions caused by natural gas leaks occur a few times each year. Individual homes, small businesses and other structures are most frequently affected when an internal leak builds up gas inside the structure. Frequently, the blast is powerful enough to significantly damage a building but leave it standing. In these cases, the people inside tend to have minor to moderate injuries. Occasionally, the gas can collect in high enough quantities to cause a deadly explosion, disintegrating one or more buildings in the process. The gas usually dissipates readily outdoors, but can sometimes collect in dangerous quantities if flow rates are high enough. However, considering the tens of millions of structures that use the fuel, the individual risk of using natural gas is very low.

Natural gas heating systems are a minor source of carbon monoxide deaths in the United States. According to the US Consumer Product Safety Commission (2008), 56 per cent of unintentional deaths from non-fire CO poisoning were associated with engine-driven tools like gas-powered generators and lawnmowers. Natural gas heating systems accounted for 4 per cent of these deaths. Improvements in natural gas furnace designs have greatly reduced CO poisoning concerns. Detectors are also available that warn of carbon monoxide and/or explosive gas (methane, propane, etc.).

Energy content, statistics, and pricing

Natural gas prices at the Henry Hub in US dollars per million BTUs ($/mmbtu).

Comparison of natural gas prices in Japan, United Kingdom, and United States, 2007-2011

Quantities of natural gas are measured in normal cubic meters (corresponding to 0 °C at 101.325 kPa) or in standard cubic feet (corresponding to 60 °F (16 °C) and 14.73 psia). The gross heat of combustion of 1 m³ of commercial quality natural gas is around 39 MJ (≈10.8 kWh), but this can vary by several percent. This comes to about 49 MJ (≈13.5 kWh) for 1 kg of natural gas (assuming a density of 0.8 kg m⁻³, an approximate value).^{[citation needed]}

The price of natural gas varies greatly depending on location and type of consumer. In 2007, a price of $7 per 1000 cubic feet (about 25 cents per m³) was typical in the United States. The typical caloric value of natural gas is roughly 1,000 British thermal units (BTU) per cubic foot, depending on gas composition. This corresponds to around $7 per million BTU, or around $7 per gigajoule. In April 2008, the wholesale price was $10 per 1,000 cubic feet (28 m³) ($10/MMBTU).^[74] The residential price varies from 50% to 300% more than the wholesale price. At the end of 2007, this was $12–$16 per 1000 cubic feet (about 50 cents per m³).^[75] Natural gas in the United States is traded as a futures contract on the New York Mercantile Exchange. Each contract is for 10,000 MMBTU (~10,550 gigajoules), or 10 billion BTU. Thus, if the price of gas is $10 per million BTUs on the NYMEX, the contract is worth $100,000.

European Union

Gas prices for end users vary greatly across the EU.^[76] A single European energy market, one of the key objectives of the European Union, should level the prices of gas in all EU member states. Moreover, it would help to resolve supply and global warming issues.^[77]

United States

U.S. Natural Gas Marketed Production 1900 to 2012, source US EIA

In US units, one standard cubic foot 1 cubic foot (28 L) of natural gas produces around 1,028 British thermal units (1,085 kJ). The actual heating value when the water formed does not condense is the net heat of combustion and can be as much as 10% less.^[78]

In the United States, retail sales are often in units of therms (th); 1 therm = 100,000 BTU. Gas meters measure the volume of gas used, and this is converted to therms by multiplying the volume by the energy content of the gas used during that period, which varies slightly over time. Wholesale transactions are generally done in decatherms (Dth), or in thousand decatherms (MDth), or in million decatherms (MMDth). A million decatherms is roughly a billion cubic feet of natural gas. Gas sales to domestic consumers may be in units of 100 standard cubic feet (scf). The typical annual consumption of a single family residence is 1,000 therms or one RCE.

Canada

Canada uses metric measure for internal trade of petrochemical products. Consequently, natural gas is sold by the Gigajoule, cubic metre (m³) or thousand cubic metres (E3m3). Distribution infrastructure and meters almost always meter volume (cubic foot or cubic meter). Some jurisdictions, such as Saskatchewan, sell gas by volume only. Other jurisdictions, such as Alberta, gas is sold by the energy content (GJ). In these areas, almost all meters for residential and small commercial customers measure volume (m³ or ft³), and billing statements include a multiplier to convert the volume to energy content of the local gas supply.

A gigajoule (GJ) is a measure approximately equal to half a barrel (250 lbs) of oil, or 1 million BTUs, or 1000 cu ft of gas, or 28 m³ of gas. The energy content of gas supply in Canada can vary from 37 to 43 MJ per m³ depending on gas supply and processing between the wellhead and the customer.

Elsewhere

In the rest of the world, natural gas is sold in Gigajoule retail units. LNG (liquefied natural gas) and LPG (liquefied petroleum gas) are traded in metric tons or MMBTU as spot deliveries. Long term natural gas distribution contracts are signed in cubic metres, and LNG contracts are in metric tonnes (1,000 kg). The LNG and LPG is transported by specialized transport ships, as the gas is liquified at cryogenic temperatures. The specification of each LNG/LPG cargo will usually contain the energy content, but this information is in general not available to the public.

In the Russian Federation, Gazprom sold approximately 250 billion cubic metres of natural gas in 2008. In 2013 the Group produced 487.4 billion cubic meters of natural and associated gas. Gazprom supplied Europe with 161.5 billion cubic meters of gas in 2013.

Natural gas as an asset class for institutional investors

Research conducted by the World Pensions Council (WPC)^[when?] suggests that large US and Canadian pension funds and Asian and MENA area SWF investors have become particularly active in the fields of natural gas and natural gas infrastructure, a trend started in 2005 by the formation of Scotia Gas Networks in the UK by OMERS and Ontario Teachers' Pension Plan.^{[citation needed]}

Adsorbed Natural Gas (ANG)

Another way to store natural gas is adsorbing it to the porous solids called sorbents. The best condition for methane storage is at room temperature and atmospheric pressure. The used pressure can be up to 4 MPa (about 40 times atmospheric pressure) for having more storage capacity. The most common sorbent used for ANG is activated carbon (AC). Three main types of activated carbons for ANG are: Activated Carbon Fiber (ACF), Powdered Activated Carbon (PAC), activated carbon monolith.^[79]

Blood–brain barrier

From Wikipedia, the free encyclopedia

Part of a network of capillaries supplying brain cells

The astrocytes type 1 surrounding capillaries in the brain

A cortical microvessel stained for blood–brain barrier protein ZO-1

The blood–brain barrier (BBB) is a highly selective permeability barrier that separates the circulating blood from the brain extracellular fluid (BECF) in the central nervous system (CNS). The blood–brain barrier is formed by capillary endothelial cells, which are connected by tight junctions with an extremely high electrical resistivity of at least 0.1 Ω⋅m.^[1] The blood–brain barrier allows the passage of water, some gases, and lipid soluble molecules by passive diffusion, as well as the selective transport of molecules such as glucose and amino acids that are crucial to neural function. On the other hand, the blood–brain barrier may prevent the entry of lipophilic, potential neurotoxins by way of an active transport mechanism mediated by P-glycoprotein. Astrocytes are necessary to create the blood–brain barrier. A small number of regions in the brain, including the circumventricular organs (CVOs), do not have a blood–brain barrier.

The blood–brain barrier occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation.^[2] Endothelial cells restrict the diffusion of microscopic objects (e.g., bacteria) and large or hydrophilic molecules into the cerebrospinal fluid (CSF), while allowing the diffusion of small hydrophobic molecules (O₂, CO₂, hormones).^[3] Cells of the barrier actively transport metabolic products such as glucose across the barrier with specific proteins.^[4] This barrier also includes a thick basement membrane and astrocytic endfeet.^[5]

Structure

Sketch showing constitution of blood vessels inside the brain

This "barrier" results from the selectivity of the tight junctions between endothelial cells in CNS vessels that restricts the passage of solutes.^[6] At the interface between blood and the brain, endothelial cells are stitched together by these tight junctions, which are composed of smaller subunits, frequently biochemical dimers, that are transmembrane proteins such as occludin, claudins, junctional adhesion molecule (JAM), or ESAM, for example.^[4] Each of these transmembrane proteins is anchored into the endothelial cells by another protein complex that includes zo-1 and associated proteins.^[4]

The blood–brain barrier is composed of high-density cells restricting passage of substances from the bloodstream much more than do the endothelial cells in capillaries elsewhere in the body.^{[citation needed]} Astrocyte cell projections called astrocytic feet (also known as "glia limitans") surround the endothelial cells of the BBB, providing biochemical support to those cells.^[7] The BBB is distinct from the quite similar blood–cerebrospinal-fluid barrier, which is a function of the choroidal cells of the choroid plexus, and from the blood–retinal barrier, which can be considered a part of the whole realm of such barriers.^[8]

Several areas of the human brain are not on the brain side of the BBB. Some examples of this include the circumventricular organs, the roof of the third and fourth ventricles, capillaries in the pineal gland on the roof of the diencephalon and the pineal gland. The pineal gland secretes the hormone melatonin "directly into the systemic circulation",^[9] thus melatonin is not affected by the blood–brain barrier.^[10]

Development

Originally, experiments in the 1920s showed that the blood–brain barrier (BBB) was still immature in newborns. The reason for this mistake was an error in methodology (the osmotic pressure was too high and the delicate embryonal capillary vessels were partially damaged). It was later shown in experiments with a reduced volume of the injected liquids that the markers under investigation could not pass the BBB. It was reported that those natural substances such as albumin, α-1-fetoprotein or transferrin with elevated plasma concentration in the newborn could not be detected outside of cells in the brain. The transporter P-glycoprotein exists already in the embryonal endothelium.^[11]

The measurement of brain uptake of acetamide, antipyrine, benzyl alcohol, butanol, caffeine, cytosine, phenytoin, ethanol, ethylene glycol, heroin, mannitol, methanol, phenobarbital, propylene glycol, thiourea, and urea in ether-anesthetized newborns vs. adult rabbits shows that newborn rabbit and adult rabbit brain endothelia are functionally similar with respect to lipid-mediated permeability.^[12] These data confirmed no differences in permeability could be detected between newborn and adult BBB capillaries. No difference in brain uptake of glucose, amino acids, organic acids, purines, nucleosides, or choline was observed between adult and newborn rabbits.^[12] These experiments indicate that the newborn BBB has restrictive properties similar to that of the adult. In contrast to suggestions of an immature barrier in young animals, these studies indicate that a sophisticated, selective BBB is operative at birth.

Function

The blood–brain barrier acts very effectively to protect the brain from many common bacterial infections. Thus, infections of the brain are very rare. Infections of the brain that do occur are often very serious and difficult to treat. Antibodies are too large to cross the blood–brain barrier, and only certain antibiotics are able to pass.^[13] In some cases a drug has to be administered directly into the cerebrospinal fluid (CSF).^[14][15] However, drugs delivered directly to the CSF do not effectively penetrate into the brain tissue itself, possibly due to the tortuous nature of the interstitial space in the brain.^[13] The blood–brain barrier becomes more permeable during inflammation. This allows some antibiotics and phagocytes to move across the BBB. However, this also allows bacteria and viruses to infiltrate the BBB.^[13][16] An exception to the bacterial exclusion is the diseases caused by spirochetes, such as Borrelia, which causes Lyme disease,Group B streptococci which causes meningitis in newborns^[17] and Treponema pallidum, which causes syphilis. These harmful bacteria gain access by releasing cytotoxins like pneumolysin^[18] which have a direct toxic effect on brain microvascular endothelium^[19] and tight junctions.

There are also some biochemical poisons that are made up of large molecules that are too big to pass through the blood–brain barrier. This was especially important in more primitive times when people often ate contaminated food. Neurotoxins such as botulinum in the food might affect peripheral nerves, but the blood–brain barrier can often prevent such toxins from reaching the central nervous system, where they could cause serious or fatal damage.^[20]

Clinical significance

As a drug target

The blood–brain barrier (BBB) is formed by the brain capillary endothelium and excludes from the brain ∼100% of large-molecule neurotherapeutics and more than 98% of all small-molecule drugs.^[6] Overcoming the difficulty of delivering therapeutic agents to specific regions of the brain presents a major challenge to treatment of most brain disorders. In its neuroprotective role, the blood–brain barrier functions to hinder the delivery of many potentially important diagnostic and therapeutic agents to the brain. Therapeutic molecules and antibodies that might otherwise be effective in diagnosis and therapy do not cross the BBB in adequate amounts.

Mechanisms for drug targeting in the brain involve going either "through" or "behind" the BBB. Modalities for drug delivery/Dosage form through the BBB entail its disruption by osmotic means; biochemically by the use of vasoactive substances such as bradykinin; or even by localized exposure to high-intensity focused ultrasound (HIFU).^[21] Other methods used to get through the BBB may entail the use of endogenous transport systems, including carrier-mediated transporters such as glucose and amino acid carriers; receptor-mediated transcytosis for insulin or transferrin; and the blocking of active efflux transporters such as p-glycoprotein. However, vectors targeting BBB transporters, such as the transferrin receptor, have been found to remain entrapped in brain endothelial cells of capillaries, instead of being ferried across the BBB into the cerebral parenchyma.^[22] Methods for drug delivery behind the BBB include intracerebral implantation (such as with needles) and convection-enhanced distribution. Mannitol can be used in bypassing the BBB.

Nanoparticles

Nanotechnology may also help in the transfer of drugs across the BBB.^[23][24] Recently, researchers have been trying to build liposomes loaded with nanoparticles to gain access through the BBB. More research is needed to determine which strategies will be most effective and how they can be improved for patients with brain tumors. The potential for using BBB opening to target specific agents to brain tumors has just begun to be explored.

Delivering drugs across the blood–brain barrier is one of the most promising applications of nanotechnology in clinical neuroscience. Nanoparticles could potentially carry out multiple tasks in a predefined sequence, which is very important in the delivery of drugs across the blood–brain barrier.

A significant amount of research in this area has been spent exploring methods of nanoparticle-mediated delivery of antineoplastic drugs to tumors in the central nervous system. For example, radiolabeled polyethylene glycol coated hexadecylcyanoacrylate nanospheres targeted and accumulated in a rat gliosarcoma.^[25] However, this method is not yet ready for clinical trials, due to the accumulation of the nanospheres in surrounding healthy tissue.

It should be noted that vascular endothelial cells and associated pericytes are often abnormal in tumors and that the blood–brain barrier may not always be intact in brain tumors. Also, the basement membrane is sometimes incomplete. Other factors, such as astrocytes, may contribute to the resistance of brain tumors to therapy.^[26][27]

Peptides

Peptides are able to cross the blood–brain barrier (BBB) through various mechanisms, opening new diagnostic and therapeutic avenues.^[28] However, their BBB transport data are scattered in the literature over different disciplines, using different methodologies reporting different influx or efflux aspects. Therefore, a comprehensive BBB peptide database (Brainpeps) was constructed to collect the BBB data available in the literature. Brainpeps currently contains BBB transport information with positive as well as negative results. The database is a useful tool to prioritize peptide choices for evaluating different BBB responses or studying quantitative structure-property (BBB behaviour) relationships of peptides. Because a multitude of methods have been used to assess the BBB behaviour of compounds, we classified these methods and their responses. Moreover, the relationships between the different BBB transport methods have been clarified and visualized.^[29]

Casomorphin is a heptapeptide and could be able to pass the BBB.^[30]

Disease

Meningitis

Meningitis is an inflammation of the membranes that surround the brain and spinal cord (these membranes are known as meninges). Meningitis is most commonly caused by infections with various pathogens, examples of which are Streptococcus pneumoniae and Haemophilus influenzae. When the meninges are inflamed, the blood–brain barrier may be disrupted.^[13] This disruption may increase the penetration of various substances (including either toxins or antibiotics) into the brain. Antibiotics used to treat meningitis may aggravate the inflammatory response of the central nervous system by releasing neurotoxins from the cell walls of bacteria - like lipopolysaccharide (LPS).^[31] Depending on the causative pathogen, whether it is bacterial, fungal, or protozoan, treatment with third-generation or fourth-generation cephalosporin or amphotericin B is usually prescribed.^[32]

Brain abscess

A brain or cerebral abscess, like other abscesses is caused by inflammation and collection of lymphatic cells and infected material originating from a local or remote infection. Brain abscess is a rare, life-threatening condition. Local sources may include infections of the ear, the oral cavity and teeth, the paranasal sinuses, or epidural abscess. Remote sources may include infections in the lung, heart or kidney. A brain abscess may also be caused by head trauma or as a complication of surgery. In children cerebral abscesses are usually linked to congenital heart disease.^[33] In most cases, 8–12 weeks of antibacterial therapy is required.^[13]

Epilepsy

Epilepsy is a common neurological disease that is characterized by recurrent and sometimes untreatable seizures. Several clinical and experimental data have implicated the failure of blood–brain barrier function in triggering chronic or acute seizures.^{[34][35][36][37][38]} Some studies implicate the interactions between a common blood protein (albumin) and astrocytes.^[39] These findings suggest that acute seizures are a predictable consequence of disruption of the BBB by either artificial or inflammatory mechanisms. In addition, expression of drug resistance molecules and transporters at the BBB are a significant mechanism of resistance to commonly used anti-epileptic drugs.^[40][41]

Multiple sclerosis

Multiple sclerosis (MS) is considered to be an auto-immune and neurodegenerative disorder in which the immune system attacks the myelin that protects and electrically insulates the neurons of the central and peripheral nervous systems. Normally, a person's nervous system would be inaccessible to the white blood cells due to the blood–brain barrier. However, magnetic resonance imaging has shown that when a person is undergoing an MS "attack," the blood–brain barrier has broken down in a section of the brain or spinal cord, allowing white blood cells called T lymphocytes to cross over and attack the myelin. It has sometimes been suggested that, rather than being a disease of the immune system, MS is a disease of the blood–brain barrier.^[42] The weakening of the blood–brain barrier may be a result of a disturbance in the endothelial cells on the inside of the blood vessel, due to which the production of the protein P-glycoprotein is not working well.^[43]

There are currently active investigations into treatments for a compromised blood–brain barrier. It is believed that oxidative stress plays an important role into the breakdown of the barrier. Anti-oxidants such as lipoic acid may be able to stabilize a weakening blood–brain barrier.^[44]

Neuromyelitis optica

Neuromyelitis optica, also known as Devic's disease, is similar to and is often confused with multiple sclerosis. Among other differences from MS, a different target of the autoimmune response has been identified. Patients with neuromyelitis optica have high levels of antibodies against a protein called aquaporin 4 (a component of the astrocytic foot processes in the blood–brain barrier).^[45]

Late-stage neurological trypanosomiasis (Sleeping sickness)

Late-stage neurological trypanosomiasis, or sleeping sickness, is a condition in which trypanosoma protozoa are found in brain tissue. It is not yet known how the parasites infect the brain from the blood, but it is suspected that they cross through the choroid plexus, a circumventricular organ.

Progressive multifocal leukoencephalopathy (PML)

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system that is caused by reactivation of a latent papovavirus (the JC polyomavirus) infection, that can cross the BBB. It affects immune-compromised patients and it is usually seen with patients suffering from AIDS.

De Vivo disease

De Vivo disease (also known as GLUT1 deficiency syndrome) is a rare condition caused by inadequate transportation of the sugar glucose across the blood–brain barrier, resulting in developmental delays and other neurological problems. Genetic defects in glucose transporter type 1 (GLUT1) appears to be the primary cause of De Vivo disease.^[46][47]

Alzheimer's disease

Some evidence indicates^[48] that disruption of the blood–brain barrier in Alzheimer's disease patients allows blood plasma containing amyloid beta (Aβ) to enter the brain where the Aβ adheres preferentially to the surface of astrocytes. These findings have led to the hypotheses that (1) breakdown of the blood–brain barrier allows access of neuron-binding autoantibodies and soluble exogenous Aβ42 to brain neurons and (2) binding of these auto-antibodies to neurons triggers and/or facilitates the internalization and accumulation of cell surface-bound Aβ42 in vulnerable neurons through their natural tendency to clear surface-bound autoantibodies via endocytosis.
Eventually the astrocyte is overwhelmed, dies, ruptures, and disintegrates, leaving behind the insoluble Aβ42 plaque. Thus, in some patients, Alzheimer's disease may be caused (or more likely, aggravated) by a breakdown in the blood–brain barrier.^[49]

Cerebral edema

Cerebral edema is the accumulation of excess water in the extracellular space of the brain, which can result when hypoxia causes the blood–brain barrier to open.

Prion and prion-like diseases

Many neurodegenerative diseases including alpha-synucleinopathies (Parkinson's, PSP, DLBP) and tauopathies (Alzheimer's) are thought to result from seeded misfolding from pathological extracellular protein variants. This prion-like hypothesis is gaining support in numerous studies in vitro and involving in vivo intracerebral injection of brain lysates, extracted protein (tau, alpha-synuclein) and synthetically generated fibers (PFFs in alpha-synucleinopathies). These proteins are also detectable in increasing amounts in the plasma of patients suffering from these conditions (particularly total alpha-synuclein in Parkinson's disease patients). The extent to which and the mechanisms by which these prion-like proteins can penetrate the blood–brain barrier is currently unknown.

HIV encephalitis

It is believed^[50] that latent HIV can cross the blood–brain barrier inside circulating monocytes in the bloodstream ("Trojan horse theory") within the first 14 days of infection. Once inside, these monocytes become activated and are transformed into macrophages. Activated macrophages release virions into the brain tissue proximate to brain microvessels. These viral particles likely attract the attention of sentinel brain microglia and perivascular macrophages initiating an inflammatory cascade that may cause a series of intracellular signaling in brain microvascular endothelial cells and damage the functional and structural integrity of the BBB.^[51] This inflammation is HIV encephalitis (HIVE). Instances of HIVE probably occur throughout the course of AIDS and are a precursor for HIV-associated dementia (HAD). The premier model for studying HIV and HIVE is the simian model.

Rabies

During lethal rabies infection of mice, the blood–brain barrier (BBB) does not allow anti-viral immune cells to enter the brain, the primary site of rabies virus replication. This aspect contributes to the pathogenicity of the virus and artificially increasing BBB permeability promotes viral clearance. Opening the BBB during rabies infection has been suggested as a possible novel approach to treating the disease, even though no attempts have yet been made to determine whether or not this treatment could be successful.^{[original research?]}

History

Paul Ehrlich was a bacteriologist studying staining, a procedure that is used in many microscopic studies to make fine biological structures visible using chemical dyes. As Ehrlich injected some of these dyes (notably the aniline dyes that were then widely used), the dye stained all of the organs of some kinds of animals except for their brains. At that time, Ehrlich attributed this lack of staining to the brain simply not picking up as much of the dye.^[52]

However, in a later experiment in 1913, Edwin Goldmann (one of Ehrlich's students) injected the dye into the cerebro-spinal fluids of animals' brains directly. He found that in this case the brains did become dyed, but the rest of the body did not. This clearly demonstrated the existence of some sort of compartmentalization between the two. At that time, it was thought that the blood vessels themselves were responsible for the barrier, since no obvious membrane could be found. The concept of the blood–brain barrier (then termed hematoencephalic barrier) was proposed by a Berlin physician, Lewandowsky, in 1900.^[53] It was not until the introduction of the scanning electron microscope to the medical research fields in the 1960s that the actual membrane could be observed and proved to exist.