Chronic daily administration of selegiline and EGb 761 increases brain's resistance to ischemia in mice

Brief cerebral ischemia is reported to cause selective neuronal necrosis, a poptotic cell death, silent infarcts and, when recurrent, cognitive decline . Acute administration of selegiline and EGb 761 have been shown to have an ti-apoptotic and neuroprotective effects in experimental ischemia. Their da ily use is currently advised to slow down cognitive decline in patients wit h vascular dementia. Hence, unlike previous studies, we studied the neuropr otective action of chronic daily administration of these drugs in Swiss mic e subjected to 30-min middle cerebral artery occlusion and 72 h of reperfus ion since this model was reported to induce a slowly evolving infarct with profuse apoptotic cell death. Infarct area was evaluated by H&E staining on coronal brain sections and, apoptotic cells were identified by histologica l criteria, terminal transferase-mediated d-UTP nick-end labeling (TUNEL) a nd by immunohistochemical detection of caspase-cleaved actin fragments (fra ctin). Fifty-one mice received daily intraperitoneal injections of 10 mg/kg selegiline (n = 18) or 50 mg/kg EGb 761 (n = 17) or equal volume of saline (n = 16) for 10-14 days before but not on the day of insult. The infarct v olume, number of TUNEL- and fractin-positive cells were significantly reduc ed in treatment groups by 30, 42 and 51% (selegiline) and, 27, 27 and 29% ( EGb 761), respectively. These data suggest that prophylactic use of selegil ine and EGb 761 could increase the brain's resistance to mild ischemic inju ry. (C) 2001 Elsevier Science B.V. All rights reserved.