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Motor evoked potentials in a rhesus macaque model of neuro-AIDS
L A Raymond1, D Wallace, J K Marcario
1Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City 66160, USA.
Abstract:
Previous work using bone marrow passaged SIVmac239 (simian immunodeficiency virus) has shown that macrophage tropic strains of this virus enter the rhesus macaque brain early following inoculation (Sharma et al, 1992; Desrosiers et al, 1991; Zhu et al, 1995; and Narayan et al, 1997). As part of an effort to more fully characterize the extent of neurologic impairment associated with SIV infection of the brain, we used transcranial electrical stimulation of motor cortex and the spinal cord to evoke EMG potentials in two forelimb (EDC and APB) and two hindlimb (LG and AH) muscles. The latencies, magnitudes and thresholds of motor evoked potentials (MEPs) recorded from nine monkeys infected with neurovirulent SIVmac R71/17E were compared to pre-inoculation records from the same monkeys. Seven of nine monkeys developed simian AIDS within 4 months of inoculation and were euthanized. Two monkeys remained free of AIDS-related clinical illness for over 18 months following inoculation. Six of the seven monkeys with rapidly progressing disease showed post-inoculation latency increases ( > or = 2 s.d. of control) in at least one cortical MEP. Increases in cortical MEP latency ranged from 21-97% in different monkeys. All seven rapidly progressing animals showed post-inoculation increases in at least one spinal cord MEP latency. Maximum spinal cord MEP latency increases ranged from 22-147%. Increases in central conduction time (CCT) ranged up to 204% and exceeded two standard deviations of control in four monkeys. Neither of the two monkeys with slowly progressing disease showed significant increases in either cortical or spinal cord MEP latency or CCT. Only the monkeys with rapidly progressing disease exhibited classic AIDS-related neuropathology, although there was no consistent relationship between the severity of neuropathology and the extent of MEP abnormalities. In conclusion, our results demonstrate clear deficits in the functional integrity of both central and peripheral motor system structures associated with SIV infection and further support the use of SIV-infected rhesus macaques as a model of neuro-AIDS.
Insights
Simian immunodeficiency virus (SIV) infection impairs motor function in rhesus macaques, causing significant delays in nerve signal transmission. Rapidly progressing SIV disease correlated with motor evoked potential abnormalities, supporting its use as a neuro-AIDS model.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Macrophage-tropic simian immunodeficiency virus (SIV) strains infect the rhesus macaque brain early post-inoculation.
- Previous studies indicate SIV's neuroinvasive potential, necessitating further characterization of neurological impairment.
Purpose of the Study:
- To assess the functional integrity of the central and peripheral motor systems in SIV-infected rhesus macaques.
- To correlate SIV-induced neuropathology with motor evoked potential (MEP) abnormalities.
Main Methods:
- Transcranial electrical stimulation of the motor cortex and spinal cord to evoke MEPs in forelimb and hindlimb muscles.
- Comparison of pre- and post-inoculation MEP latencies, magnitudes, and thresholds in nine SIVmac R71/17E infected monkeys.
- Assessment of neuropathology in relation to MEP findings.
Main Results:
- Seven of nine monkeys rapidly developed simian AIDS and showed significant increases in cortical and spinal cord MEP latencies (up to 97% and 147%, respectively).
- Central conduction time (CCT) increased up to 204% in four rapidly progressing cases.
- Two slowly progressing cases showed no significant MEP abnormalities.
- Neuropathology was present only in rapidly progressing cases, but without a clear correlation to MEP deficits.
Conclusions:
- SIV infection causes functional deficits in both central and peripheral motor systems.
- MEP abnormalities are associated with rapidly progressing SIV disease and neuropathology.
- SIV-infected rhesus macaques serve as a valuable model for studying neuro-AIDS.