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Auditory brainstem responses in a Rhesus Macaque model of neuro-AIDS
L A Raymond1, D Wallace, N E Berman
1Department of Molecular & Integrative Physiology, Smith Mental Retardation and Human Development Research Centre, University of Kansas Medical Center, Kansas City 66160, USA.
Abstract:
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.
Insights
Simian immunodeficiency virus (SIVmac) infection in rhesus macaques caused auditory brainstem response abnormalities and neuropathology similar to human HIV. This supports macaques as a model for HIV-related neurological disease.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Simian immunodeficiency virus (SIV) infection in non-human primates serves as a model for human immunodeficiency virus (HIV) infection.
- Neurological complications are a significant concern in HIV disease.
- Neurovirulent SIV strains can induce pathological changes in the central nervous system.
Purpose of the Study:
- To investigate the neurological effects of dual SIVmac strain inoculation in rhesus macaques.
- To assess auditory pathway function using Auditory Brainstem Responses (ABRs) in SIV-infected macaques.
- To correlate physiological changes with histopathological findings in a primate model of HIV-related neurological disease.
Main Methods:
- Nine rhesus macaques were inoculated with neurovirulent SIVmac strains (R71 and 17E).
- Auditory Brainstem Responses (ABRs) were recorded pre- and post-inoculation.
- Histopathological examination of brain tissue was performed.
- Disease progression and latency were monitored.
Main Results:
- Increases in ABR peak and interpeak latencies correlated with SIV disease progression.
- Significant latency increases were observed for all ABR peaks and interpeak intervals, particularly in end-stage disease.
- Histopathology revealed multifocal lesions in the brain and auditory structures.
- Correlation between ABR changes and neuropathology was observed, though not absolute.
Conclusions:
- SIVmac R71/17E infection in rhesus macaques mimics physiological and pathological aspects of HIV-related neurological disease in humans.
- The study validates the use of SIVmac-infected rhesus macaques as a relevant animal model for studying HIV-associated neurological disorders.
- ABRs are a sensitive tool for monitoring SIV-induced neurological dysfunction in this model.