THE NEUROPATHOLOGY OF INTRACEREBROVENTRICULAR T-BUTYLHYDROPEROXIDE

t-Butylhydroperoxide can be used as a model oxidative stress-inducing agent in the brain following intracerebroventricular administration. M ice were treated with saline, t-butanol, or t-butylhydroperoxide. t-Bu tanol is the major metabolite of t-butylhydroperoxide. t-Butylhydroper oxide had a number of effects, including that it damages dopaminergic, cholinergic, and GABAergic neurons as demonstrated immunohistochemica lly. Electron microscopic examination demonstrated that astrocytes, ol igodendrocytes, endothelial cells, pericytes, and neurons are damaged by t-butylhydroperoxide. Dopamine and its metabolites were affected in a number of brain regions, as were serotonin and its metabolite. Chol ine acetyl transferase activity was decreased in the striatum. Edema w as apparent as assessed by tissue protein levels. There was evidence o f lipid peroxidation produced by t-butylhydroperoxide in the midbrain. t-Butylhydroperoxide is a neurotoxin that may be useful in understand ing the unexpected ways the brain responds to oxidative stress.