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Early brain injury in the SIVmacaque model of AIDS

González, R. Gilberto; Cheng, Leo L.a; Westmoreland, Susan V.b; Sakaie, Ken E.; Becerra, Lino R.; Lee, Patricia L.; Masliah, Eliezerc; Lackner, Andrew A.b

Basic Science

Objective: To specify the type and severity of cellular damage in the central nervous system soon after infection and at later stages of disease in the SIV–macaque model of AIDS.

Designand methods: Adjacent samples of frontal cortical gray matter were taken from three groups of macaques: uninfected controls (n = 4), acute (14 days post-infection; n = 4), and chronic (mean 2 years post-infection; n = 7). In vitro high resolution magnetic resonance spectroscopy of snap frozen intact tissue and quantitative neuropathology measurements of synaptophysin, calbindin, and glial fibrillary acidic protein (GFAP) in formalin-fixed tissue were performed.

Results: Losses in n-acetylaspartate and calbindin (indicating neuronal injury and/or death) and decreases in synaptophysin immunoreactivity (indicating synaptodendritic injury) were detected along with increases in GFAP (indicating reactive gliosis). Cellular injury worsened progressively with increased time after infection.

Conclusions: These results are the first direct evidence that neuronal injury occurs soon after infection. The exacerbation of injury with time suggests a connection between the early response of the central nervous system and dementia, which occurs late in the course of infection. This connection may have broad implications for the study of and the development of therapies for damage of the central nervous system by HIV.

From the Neuroradiology Division, and the aDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, the bNew England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts, and the cDepartments of Neurosciences and Pathology, University of California, San Diego, LaJolla, California, USA.

Requests for reprints to: R. Gilberto González, Neuroradiology Division, GRB 285, Massachusetts General Hospital, Fruit Street, Boston, MA 02114, USA.

Received: 6 March 2000;

revised: 4 October 2000; accepted: 10 October 2000.

Sponsorship: Supported by NIH grants RR13213 (R.G.G.), NS34626 (R.G.G.), NS30769 (A.L.), NS35732 (AL), RR00168 (N.E.R.P.R.C.), MH45294 (E.M.), MH59745 (E.M.), DA12065 (E.M.). A. Lackner is a recipient of an Elizabeth Glaser Scientist Award.

© 2000 Lippincott Williams & Wilkins, Inc.