Early-onset tolerance in rat global cerebral ischemia induced by a mitochondrial inhibitor.
It was studied whether a subtoxic dose of the mitochondrial neurotoxin, 3-nitropropionic acid (3-NPA), can initiate early-onset tolerance induction for subsequent ischemic injury. Wistar rats were pretreated for 3 h by intraperitoneal 3-NPA (20 mg/kg body weight; n=13) or solvent (n=12). Fifteen minutes global cerebral ischemia was induced by bilateral carotid artery occlusion and hypobaric hypotension. rCBF and tissue hemoglobin oxygen saturation were measured by laser Doppler scanning and a microspectrophotometric method. Ischemic insult and brain temperature were identical in both groups. Body weight and neurological scores recovered in the pretreated group but further deteriorated in the non-treated group (P<0.05). Quantitative histology demonstrated a better neuronal density in neocortex and hippocampal CA2, CA3, and CA4 of pretreated animals (P<0.05).
Nakase
H
H
Institute for Neurosurgical Pathophysiology, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55101, Mainz, Germany.
Heimann
A
A
Uranishi
R
R
Riepe
M W
MW
Kempski
O
O
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003292:Convulsants / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology*; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D003292:Convulsants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid