Our primary focus is to examine the immune response during viral encephalitis. A model of HIV encephalitis in severe combined immunodeficient (SCID) mice was developed whereby HIV-infected or uninfected human mononuclear cells are injected intracerebrally. Pathologically these brains closely resemble the changes seen in humans with this condition. In addition these mice exhibit behavioral abnormalities similar to those seen in humans with HIV dementia. Currently we are funded to study: 1) the effects of highly active antiretroviral therapy administration in HIV encephalitis in SCID mice, 2) the role of Interferon-alpha in HIV encephalitis in SCID mice, 3) the effects of opiate administration in HIV encephalitis in SCID mice and 4) the examination of different viral clades on the development of HIV encephalitis in SCID mice. Ultimately, we will identify mechanisms involved in the pathogenesis of HIV encephalitis so that better treatment strategies can be developed.

Techniques currently being used include tissue sectioning, immunohistochemical staining methods, in situ TUNEL assay, and other procedures for the pathological evaluation of tissue sections. We use ELISA and Western blots for protein quantitation. RNA is extracted from brain for quantitative ribonuclease protection assays (RPA) as well as quantitative traditional and real time PCR for detection of various mRNA’s of interest. These include various cytokines, chemokines, HIV genes and others. We also monitor these mice with different behavioral tests including the water radial arm maze. Other research interests include the immunopathogenesis of experimental autoimmune encephalomyelitis and spinal cord injury in rodent models.