Brief cerebral ischemia is reported to cause selective neuronal necrosis, apoptotic cell death, silent infarcts and, when recurrent, cognitive decline. Acute administration of selegiline and EGb 761 have been shown to have anti-apoptotic and neuroprotective effects in experimental ischemia. Their daily use is currently advised to slow down cognitive decline in patients with vascular dementia. Hence, unlike previous studies, we studied the neuroprotective action of chronic daily administration of these drugs in Swiss mice subjected to 30-min middle cerebral artery occlusion and 72 h of reperfusion 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 histological criteria, terminal transferase-mediated d-UTP nick-end labeling (TUNEL) and by immunohistochemical detection of caspase-cleaved actin fragments (fractin). 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 volume, number of TUNEL- and fractin-positive cells were significantly reduced in treatment groups by 30, 42 and 51% (selegiline) and, 27, 27 and 29% (EGb 761), respectively. These data suggest that prophylactic use of selegiline and EGb 761 could increase the brain's resistance to mild ischemic injury. (C) 2001 Elsevier Science B.V. All rights reserved.