Protective Effect of 4-Methoxy Benzyl Alcohol on the Blood–Brain Barrier after Cerebral Ischemia Reperfusion Injury

• Published in: Journal of stroke and cerebrovascular diseases Vol. 26; no. 6; pp. 1258 - 1265
• Main Authors: He, Fangyan, MS, Duan, Xiaohua, MS, Dai, Rong, BS, Li, Yan, MS, Lin, Qing, BS
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2017
• Subjects: 4-Methoxy benzyl alcohol; Animals; Anisoles - pharmacology; Aquaporin 4 - metabolism; aquaporin-4; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - pathology; blood–brain barrier; Capillary Permeability - drug effects; Cardiovascular; Claudin-5 - metabolism; Cytoprotection; Disease Models, Animal; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - pathology; Infarction, Middle Cerebral Artery - prevention & control; Male; Neurology; Neuroprotective Agents - pharmacology; Nitric Oxide - metabolism; nitric oxide synthase; Nitric Oxide Synthase Type I - metabolism; Nitric Oxide Synthase Type II - metabolism; Occludin - metabolism; Rats, Sprague-Dawley; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; tight junction; Tight Junctions - drug effects; Tight Junctions - metabolism; Tight Junctions - pathology; 4-Methoxy benzyl alcohol; blood–brain barrier; nitric oxide synthase; aquaporin-4; tight junction
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2017.01.018

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.