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-n itropropionic acid (3-NPA), can initiate early-onset tolerance induction fo r subsequent ischemic injury. Wistar rats were pretreated for 3 h by intrap eritoneal 3-NPA (20 mg/kg body weight; n = 13) or solvent (n = 12). Fifteen minutes global cerebral ischemia was induced by bilateral carotid artery o cclusion and hypobaric hypotension. rCBF and tissue hemoglobin oxygen satur ation were measured by laser Doppler scanning and a microspectrophotometric method. Ischemic insult and brain temperature were identical in both group s. Body weight and neurological scores recovered in the pretreated group bu r further deteriorated in the non-treated group (P < 0.05). Quantitative hi stology demonstrated a better neuronal density in neocortex and hippocampal CA2, CA3, and CA4 of pretreated animals (P < 0.05). (C) 2000 Elsevier Scie nce Ireland Ltd. All rights reserved.