title: Protective Effect of 4-Methoxy Benzyl Alcohol on the Blood-Brain Barrier after Cerebral Ischemia Reperfusion Injury.
abstract: Damage of the blood-brain barrier (BBB) during the process of cerebral ischemic injury is a key factor that influences the therapeutic efficacy to the cerebral ischemic injury. This work was designed to investigate the mechanisms underlying the protective effects of 4-methoxy benzyl alcohol (4-MA) on the BBB by developing a cerebral ischemia/reperfusion model of rats (MCAO/R). The MCAO/R was developed through a thread embolism method. The neurologic scales, the brain infarct rate, and the Evans blue (EB) contents of the brains were detected. Meanwhile, the release of nitric oxide (NO) and activities of NO synthase (NOS) in brain tissues were measured. Western blotting analyses were also used to assess the protein expressions of aquaporin-4 (AQP-4), occludin, and claudin-5 in brain tissue. After rats were pretreated with different concentrations of 4-MA, the neurologic scores, the infarct rate, and the EB contents in the brain tissues were significantly decreased. The release of NO and the activities of neuronal NOS and inducible NOS were notably inhibited. Furthermore, the protein expression of AQP-4 was markedly decreased, whereas the protein expressions of claudin-5 and occludin were significantly increased. In conclusion, the 4-MA decreases the permeability of BBB when focal cerebral ischemia occurs. The inhibition of the NOS pathways, the attenuation of the protein expression of AQP-4, and the enhancement of the expressions of the tight junction proteins might contribute to the protective effects of 4-MA on the BBB.
authors.affiliation: The Department of Pharmacology, Yunnan University of Traditional Chinese Medicine, Kunming, China.
authors.forename: Fangyan
authors.initials: F
authors.lastname: He
authors.affiliation: The Key Modern Research Laboratory for Ethno-Pharmacognosy of Yunnan Higher School, Yunnan University of Traditional Chinese Medicine, Kunming, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Duan
authors.affiliation: The Department of Pharmacology, Yunnan University of Traditional Chinese Medicine, Kunming, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Dai
authors.affiliation: The Department of Pharmacology, Yunnan University of Traditional Chinese Medicine, Kunming, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Department of Pharmacology, Yunnan University of Traditional Chinese Medicine, Kunming, China. Electronic address: 1609627617@qq.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
mesh_terms: D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D051401:Aquaporin 4 / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects*; D062507:Claudin-5 / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000840:Anisoles; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D062507:Claudin-5; C491510:Cldn5 protein, rat; D018696:Neuroprotective Agents; D062793:Occludin; C568987:Ocln protein, rat; D009569:Nitric Oxide; C066943:anisyl alcohol; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat
keywords: 4-Methoxy benzyl alcohol; aquaporin-4; blood–brain barrier; nitric oxide synthase; tight junction