The neuropathology of intracerebroventricular t-butylhydroperoxide.
t-Butylhydroperoxide can be used as a model oxidative stress-inducing agent in the brain following intracerebroventricular administration. Mice were treated with saline, t-butanol, or t-butylhydroperoxide. t-Butanol is the major metabolite of t-butylhydroperoxide. t-Butylhydroperoxide had a number of effects, including that it damages dopaminergic, cholinergic, and GABAergic neurons as demonstrated immunohistochemically. Electron microscopic examination demonstrated that astrocytes, oligodendrocytes, 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. Choline acetyl transferase activity was decreased in the striatum. Edema was apparent as assessed by tissue protein levels. There was evidence of lipid peroxidation produced by t-butylhydroperoxide in the midbrain. t-Butylhydroperoxide is a neurotoxin that may be useful in understanding the unexpected ways the brain responds to oxidative stress.
Adams
J D
JD
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California.
Klaidman
L K
LK
Huang
Y M
YM
Cheng
J J
JJ
Wang
Z J
ZJ
Nguyen
M
M
Knüsel
B
B
Kuda
A
A
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000473:pathology*; D001927:Brain Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology*; D001929:Brain Edema / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D004563:Electrochemistry; D005609:Free Radicals; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000201:enzymology / Q000473:pathology; D010545:Peroxides / Q000008:administration & dosage / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000008:administration & dosage / Q000633:toxicity*; D020122:tert-Butylhydroperoxide
D015306:Biogenic Monoamines; D005609:Free Radicals; D009419:Nerve Tissue Proteins; D010545:Peroxides; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D002795:Choline O-Acetyltransferase; D004298:Dopamine