Scid mice with hiv encephalitis develop behavioral abnormalities

SCID mice inoculated intracerebrally (1C) with preinfected (HIV) human macrophages develop brain pathology similar to that in humans with HIV encephalitis. This includes immimocytochemical detection in brain sections of HIV-infected macrophages and multinucleated giant cells, and significant astrogliosis compared to controls (mice injected 1C with uninfected human macrophages). These xenografts survive about 1 month. To develop a model of chronic HIV encephalitis and determine if chronically infected mice develop behavioral abnormalities similar to the human condition, we reinoculated SCID mice 1C every 4 weeks with either preinfected human macrophages (infected mice), uninfected human macrophages, or no inoculation; these groups were monitored for behavioral abnormalities. For 3 months after the first inoculation (total of 4 inoculations) each mouse was monitored on Stoelting activity monitors for 24 hours twice a month. There was no significant difference between groups in the amount of general activity during their normal day to day routine. However, the acquisition of a Morris maze problem by infected mice 3 1/2 months after the first inoculation was deficient in comparison to mice inoculated with uninfected macrophages or uninoculated mice. Ongoing studies are investigating the potential relationships between:(l) the histopathology such as the presence and amount of macrophages, HIV, and astrogliosis, (2) cytokine production (in situ detection and quantitative PCR for mllNA) such as TNF-alpha and others, and (3) the behavioral abnormalities.