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Jefferson immunology researchers halt lethal rabies infection in brain
Date:9/4/2007

und that the PLSJL mice, which genetically produce less inflammatory-regulating hormone, were less likely to die from the rabies infection, possibly because they are more prone to develop a stronger inflammatory response and more likely to have opened brain barriers. Conversely, they also found that despite a strong immune response, the rabies-infected 129/SvEv mice died and were less likely to have open barriers.

When they gave the PLSJL mice the anti-inflammatory steroid hormone DHEA, the brain inflammation decreased, the barriers permeability lessened, and the death rate more than doubled.

The researchers thought that if some rabies-infected PLSJL mice died because the virus overwhelms the immune system T and B cells already in the brain and CNS, then opening the barrier even more would enable more immune cells to reach CNS tissue and fight the virus. They subsequently gave animals experimental autoimmune encephalitis (EAE), which causes an inflammatory response and the barrier to open. As a result, a higher percentage of animals survived the infection.

Halting rabies in the brain

In the future, one of the things we want to do is tone down the inflammatory response caused by EAE and minimize the pathogenesis, yet deliver immune cells to the CNS, says Dr. Hooper, who is also associate director of Jeffersons Center for Neurovirology. The trick to survival might be to open the barrier and deliver effectors to the CNS.

The data suggest that the CNS cells are developing T and B cells effectively, but that delivery to the CNS is impaired, Dr. Hooper explains. It might mean that the communication between the CNS and the immune system is somehow blocked. Perhaps when the disease gets further along, it triggers certain hormones that prevent the brain barrier from opening in response to immune signals. Were trying to develop a better way to open the barrier and let these immune cells in.

While they would like t
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Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
Source:Eurekalert

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