title: Acute hypertension induces brain injury and blood-brain barrier disruption through reduction of claudins mRNA expression in rat.
abstract: The present study examined genes transcription of tight junction (TJs) proteins of the blood-brain barrier (BBB) and detrimental effects on the brain tissue after acute hypertension.The experiment was performed in two groups of rats, sham and hypertensive. Rats were made acutely hypertensive by aortic constriction above the renal arteries. After 8 days, arterial pressure was recorded and BBB permeability was evaluated by the Evans blue dye extravasations (EBE) technique. Quantitative RT-PCR was used for assessment of mRNA expression of claudins (claudin-3, 5 & 12). Superoxide dismutase (SOD) and catalase activity, as well as glutathione and malondialdehyde content were determined by biochemical methods. Aortic constriction significantly enhanced arterial pressure and EBE of hypertensive rats by 35% and 76%, respectively. Enzyme activity of SOD and catalase were significantly lower in hypertensive rats. Hypertension significantly decreased the brain glutathione content and increased the brain malondialdehyde level. Also, the mRNA levels of claudins (3, 5 & 12) proteins significantly decreased in response to hypertension. Our findings indicated that acutely elevated arterial pressure provokes brain microvascular permeability by diminution of claudins genes transcription in the endothelial cells of BBB. Our results also showed that short-term hypertension impairs the antioxidant defense system of brain and induces brain injury through oxidative stress.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address: Mohammadi.mohammadt@yahoo.com.
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Mohammadi
authors.affiliation: Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Golam Abbas
authors.initials: GA
authors.lastname: Dehghani
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002199:Capillary Permeability; D002374:Catalase / Q000378:metabolism; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D057167:Claudins; D012333:RNA, Messenger; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase
keywords: Antioxidant system; Blood–brain barrier; Claudins; Hypertension; Vascular permeability