Auditory brainstem responses in a Rhesus Macaque model of neuro-AIDS.
Nine rhesus macaques (Macaca mulatta) were inoculated with a combination of two passaged strains of SIVmac (R71 and 17E), both of which are known to be neurovirulent. Auditory brainstem responses (ABRs) were recorded at regular intervals from these animals both before and after inoculation. Increases in ABR peak and interpeak latency were observed corresponding to progression of SIV disease. Post-inoculation increases in latency were observed for all five peaks of the ABR and for interpeak intervals I-V and III-V. The largest increases in latency were associated with end-stage disease. Within 14 weeks of inoculation, all but two animals developed end-stage simian AIDS and were euthanized. Histopathological examination revealed multifocal lesions in the cerebral gray and white matter as well as in the auditory structures of the brainstem. In most animals, ABR changes were accompanied by evidence of underlying neuropathology. However, cases of severe neuropathology with no ABR abnormalities and vice versa were also noted. Though in a much shorter time frame, SIVmac R71/17E produced both physiological and histopathological abnormalities similar to those associated with HIV disease in humans. These results further support the SIVmac R71/17E infected rhesus macaque as an animal model of HIV related neurological disease in humans.
Raymond
L A
LA
Department of Molecular & Integrative Physiology, Smith Mental Retardation and Human Development Research Centre, University of Kansas Medical Center, Kansas City 66160, USA.
Wallace
D
D
Berman
N E
NE
Marcario
J
J
Foresman
L
L
Joag
S V
SV
Raghavan
R
R
Narayan
O
O
Cheney
P D
PD
D015526:AIDS Dementia Complex / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D000818:Animals; D001306:Auditory Pathways / Q000473:pathology; D001933:Brain Stem / Q000473:pathology / Q000503:physiopathology; D018791:CD4 Lymphocyte Count; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology*; D015683:Gene Products, gag / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D001523:Mental Disorders; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*
C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag