Overproduction of nitric oxide intensifies brain infarction and cerebrovascular damage through reduction of claudin-5 and ZO-1 expression in striatum of ischemic brain.
Nitric oxide (NO) overproduction has been demonstrated from different NO-synthase overexpression or hyperactivity after brain ischemia. Here, we examined the effects of inhibition of NO overproduction on brain infarction, cerebrovascular damage and expression of claudin-5 and zonula occludens-1 (ZO-1) in striatum of ischemic brain. The experiment was performed in three groups of rats; sham, control ischemia and ischemic treatment. Brain ischemia was induced by 60min of middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. Treated rats received L-NAME 30min before induction of ischemia (1mg/kg, i.p.). Infarct volume and histopathological changes of ischemic striatum were assessed by TTC and LFB staining methods, respectively. Ultimately, quantitative RT-PCR was used for assessment of claudins-5 and ZO-1 expression. MCAO in the control group induced infarction (135±25mm3) at large areas of striatum in accompany with neuronal damages, whereas L-NAME significantly reduced infarction (87±16mm3) and neuronal injuries. The mRNA of ZO-1 and claudin-5 decreased in ischemic striatum, whereas inhibition of NO overproduction by L-NAME attenuated this reduction for these genes. Our findings indicated that NO overproduction after brain ischemia plays a crucial role in neuronal damage especially at striatal regions. Hence, inhibition of excessive NO production may save striatal cerebrovascular integrity of ischemic brain.
Department of Physiology and Biophysics, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address: Mohammadi.mohammadt@yahoo.com.
Mohammad Taghi
MT
Mohammadi
D000818:Animals; D020520:Brain Infarction / Q000378:metabolism / Q000473:pathology*; D002199:Capillary Permeability / Q000502:physiology; D062507:Claudin-5 / Q000096:biosynthesis*; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D062826:Zonula Occludens-1 Protein / Q000096:biosynthesis*
D062507:Claudin-5; C491510:Cldn5 protein, rat; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D009569:Nitric Oxide
Brain ischemia; Claudin-5; L-NAME; Nitric oxide; Zonula occludens-1