2008 Woodie Awards
Drug reduces damage from brain infection
Issue date: 2/28/08
A group of viral infections that can cause severe and sometimes fatal brain damage has become more common around the world in recent years. New research from the Bloomberg School of Public Health suggests a way to reduce the worst of the damage.
The viruses, called alphaviruses, are carried by mosquitoes and other insects. Viral infections sometimes infect brain tissue, causing symptoms ranging from temporary paralysis to coma or death.
A group of Hopkins researchers led by Diane Griffin outlines three mechanisms for viral-induced brain damage, formally called viral encephalitis or encephalomyelitis.
The first is pathology caused by viral infection itself. When a virus infects a cell, it takes over some of the cell's machinery and uses it to multiply and spread. This mechanism accounts for the damage of many viral infections.
A second pathway involves inflammation. Inflammation is a normal response to infection that involves the stimulation of a variety of chemical and cellular responses. Over the long term, uncontrolled inflammation can be damaging to brain tissue.
The final pathway is unique to the nervous system: excitotoxicity. Nerve cells, or neurons, work by releasing small amounts of chemicals called neurotransmitters to neighboring cells.
If a neuron is exposed to too much of one of these neurotransmitters, an amino acid called glutamate, the cell will fill with calcium ions, setting off an irreversible process of cell death.
One way neurons sense glutamate is through a membrane receptor called AMPA. It is known that chemically blocking the AMPA receptor can reduce the risk of excitotoxicity in a viral brain infection.
Griffin and her team wondered whether blocking the AMPA receptor might affect the risk of inflammation as well.
The group infected mice with Sindbis virus, a type of alphavirus that causes encephalitis in rodents. They then treated the mice with talampanel, a medically useful inhibitor, or antagonist, of the AMPA receptor.
The researchers noted the expected decrease in excitotoxic damage. Also as expected treatment with talampanel did not reduce the process of the infection itself - viral loads were unchanged in treated mice.
Interestingly, however, the treated mice also demonstrated fewer signs of inflammation. For instance, there were fewer immune cells invading into the brain tissue. There was also less activation of supporting cells in the brain called astrocytes that release various chemicals as part of the inflammatory process.
Mice treated with talampanel avoided paralysis and death as a result of viral encephalitis. Griffin's findings are significant because they show that the medication acts on two distinct and complementary pathways.
The viruses, called alphaviruses, are carried by mosquitoes and other insects. Viral infections sometimes infect brain tissue, causing symptoms ranging from temporary paralysis to coma or death.
A group of Hopkins researchers led by Diane Griffin outlines three mechanisms for viral-induced brain damage, formally called viral encephalitis or encephalomyelitis.
The first is pathology caused by viral infection itself. When a virus infects a cell, it takes over some of the cell's machinery and uses it to multiply and spread. This mechanism accounts for the damage of many viral infections.
A second pathway involves inflammation. Inflammation is a normal response to infection that involves the stimulation of a variety of chemical and cellular responses. Over the long term, uncontrolled inflammation can be damaging to brain tissue.
The final pathway is unique to the nervous system: excitotoxicity. Nerve cells, or neurons, work by releasing small amounts of chemicals called neurotransmitters to neighboring cells.
If a neuron is exposed to too much of one of these neurotransmitters, an amino acid called glutamate, the cell will fill with calcium ions, setting off an irreversible process of cell death.
One way neurons sense glutamate is through a membrane receptor called AMPA. It is known that chemically blocking the AMPA receptor can reduce the risk of excitotoxicity in a viral brain infection.
Griffin and her team wondered whether blocking the AMPA receptor might affect the risk of inflammation as well.
The group infected mice with Sindbis virus, a type of alphavirus that causes encephalitis in rodents. They then treated the mice with talampanel, a medically useful inhibitor, or antagonist, of the AMPA receptor.
The researchers noted the expected decrease in excitotoxic damage. Also as expected treatment with talampanel did not reduce the process of the infection itself - viral loads were unchanged in treated mice.
Interestingly, however, the treated mice also demonstrated fewer signs of inflammation. For instance, there were fewer immune cells invading into the brain tissue. There was also less activation of supporting cells in the brain called astrocytes that release various chemicals as part of the inflammatory process.
Mice treated with talampanel avoided paralysis and death as a result of viral encephalitis. Griffin's findings are significant because they show that the medication acts on two distinct and complementary pathways.
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