July 1, 2011 A longstanding medical mystery -- why so many people with HIV experience memory loss and other cognitive problems despite potent antiretroviral therapy -- may have been solved by researchers at Albert Einstein College of Medicine of Yeshiva University.
Their findings are published in the June 29 issue of The Journal of Neuroscience.
Even though antiretroviral treatment suppresses HIV replication and slows the progress of HIV disease, between 40 and 60 percent of HIV-infected people eventually develop mild-to-moderate neurological deficits, and up to 5 percent develop full-blown dementia. Until now, researchers have not been able to explain why these complications, collectively known as neuroAIDS, occur.
In a previous study, the Einstein researchers found that HIV infects about 5 percent of brain cells known as astrocytes. These cells bolster the blood-brain barrier, a network of blood vessels that prevents harmful substances from crossing into the brain from the bloodstream. In the present study, the researchersshow that even this low-level of astrocyte infection can profoundly damage the blood-brain barrier.
"The relatively few infected astrocytes emit toxic signals through specialized channels that kill neighboring uninfected astrocytes, ultimately weakening the blood-brain barrier and allowing harmful compounds to enter the brain," said senior author Joan Berman, Ph.D., professor of pathology and of microbiology & immunology at Einstein.
The evidence came from a laboratory model of the blood-brain barrier constructed of human cells and from examining brain tissue of macaque monkeys infected with the simian form of HIV. The results suggest that drugs capable of reducing the damaging signaling cascades triggered by HIV-infected astrocytes might help in preventing or treating neuroAIDS.
The Journal of Neuroscience paper's lead author is Eliseo Eugenin, Ph.D., assistant professor of pathology at Einstein.
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- E. A. Eugenin, J. E. Clements, M. C. Zink, J. W. Berman. Human Immunodeficiency Virus Infection of Human Astrocytes Disrupts Blood-Brain Barrier Integrity by a Gap Junction-Dependent Mechanism. Journal of Neuroscience, 2011; 31 (26): 9456 DOI: 10.1523/JNEUROSCI.1460-11.2011
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