title: [Effect of irbesartan on focal cerebral ischemia in rats].
abstract: OBJECTIVE
  To investigate whether the selective AT1 receptor antagonist irbesartan exerts neuroprotective effect on focal cerebral ischemia in normotensive rats.
  
  
  METHODS
  Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion, with the monitoring of laser Doppler flowmetry. To avoid the interaction with peripheral AT1 receptors, irbesartan was infused intracerebroventricularly (ICV) at a dose which effectively inhibited brain- but not vascular AT1 receptors. Neurological status was evaluated daily after MCAO. Rats were killed and brain samples were collected for the measurement of infarct size and immunohistochemical evaluation of apoptosis by deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling (TUNEL) and expression of activated Caspase-3 and the cleavage fragment of poly (ADP-ribose) polymerase (PARP).
  
  
  RESULTS
  Treatment with irbesartan improved significantly the neurobehavioral functions after cerebral ischemia. The infarct size was reduced about 42% on day 7 after MCAO (P < 0.05). Meanwhile,irbesartan treatment significantly decreased the number of TUNEL-positive cells in the penumbra. The expression of activated Caspase-3 and the downstream cleavage fragment of poly (ADP-ribose) polymerase in the penumbra were also inhibited by irbesartan therapy on day 3 after transient cerebral ischemia.
  
  
  CONCLUSIONS
  Angiotensin AT1 receptor antagonist exhibits neuroprotection against transient cerebral ischemia in the brain. The neuroprotective effects in ischemic tissue may be associated with its inhibition of apoptotic cell death in the penumbra.
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009.
authors.forename: Min
authors.initials: M
authors.lastname: Lou
authors.forename: Mei-Ping
authors.initials: MP
authors.lastname: Ding
authors.forename: Shu-Qun
authors.initials: SQ
authors.lastname: Wen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002544:Cerebral Infarction / Q000473:pathology; D000077405:Irbesartan; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D020547:Lateral Ventricles; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D018696:Neuroprotective Agents; D013777:Tetrazoles; D000077405:Irbesartan