EVALUATION OF THE INHIBITION OF NITRIC OXIDE PRODUCTION BY L-NAME ON BLOOD-BRAIN BARRIER PERMEABILITY AND TRANSCRIPTION OF CLAUDIN-3 AND 12 GENES AT THE SUBCORTICAL AREAS FOLLOWING CEREBRAL ISCHEMIA-REPERFUSION IN MALE RAT

Blood-brain barrier (BBB) breakdown and nitric oxide (NO) overproduction following cerebral ischemia-reperfusion extensively happens in the subcortical regions (core areas). Hence, we assessed the effects of NO inhibition by L-NAME on transcription of the transmembrane proteins claudin-3 and 12, with key role in BBB structure, at subcortical areas following cerebral ischemia-reperfusion in rat. Eighteen male Wistar rats (270-320 g) were randomly divided into three groups; sham, control ischemia and treated ischemic groups. Brain ischemia was induced by 90 min right middle cerebral artery occlusion (MCAO) followed by 24 hours reperfusion. Rats received L-NAME intraperitoneally at dose of 1 mg/kg 30 min before MCAO. Neurological deficit score (NDS), BBB permeability and transcription of the claudin-3 and 12 genes at subcortical areas were assessed 24 hours after termination of MCAO. MCAO induced neurological dysfunction (2.83±0.30) and BBB interruption in the ischemic hemispheres of control ischemic group, whereas L-NAME administration in ischemic treated rats significantly declined neurological dysfunction (1.50±0.22) and also BBB permeability. L-NAME administration in treated ischemic group also enhanced the transcription levels of caudin-3 and 12 by 76% and 71%, respectively, which declined in control ischemic group. Our findings indicate that NO inhibition in cerebral ischemia-reperfusion declines the BBB interruption and stroke outcomes through preventing from reduction of the transcription levels of caudin-3 and 12 in subcortical areas.