Interest: ethanol-induced brain damage;
ethanol protection against HIV-1 gp120 neurotoxicity
Dr. Neafsey's research focuses on two questions related to ethanol's effects
on the brain. The first question concerns the role of brain edema in ethanol-induced
brain damage, since previous work by Drs. Neafsey and Collins has shown that
brain damage following "binge" ethanol intoxication and withdrawal
in rats over 4-8 days is associated with brain edema that develops during withdrawal.
Treatment of the rats with diuretics such as furosemide prevents the brain edema
and the brain damage due to "binge" ethanol exposure, suggesting edema
may be an important causal factor in the brain damage. The second question concerns
the mechanism by which moderate (30 mM) ethanol preconditioning (MEP) prevents
the neurotoxicity in cultured organotypic hippocampal brain slices caused by
exposure to HIV-1 neurotoxic proteins such as gp120 or to the amyloid-beta protein
that is linked to Alzheimer's disease. The present hypothesis in the Collins-Neafsey
laboratories is that MEP reduces excitotoxic mechanisms and oxidative damage
triggered by elevated glutamate, since MEP prevents gp120's inhibition of glutamate
uptake by glial cells in the slices. In addition, MEP also produces an elevation
of protective heat shock proteins in the slices.
