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Protective effect of 4-Methoxy benzyl alcohol on the neurovascular unit after cerebral ischemia reperfusion injury.
Biomed Pharmacother. 2019 Oct; 118:109260.BP

Abstract

OBJECTIVE

Cerebral ischemia reperfusion injury (CIRI) is a major cause of ischemic stroke (IS) deterioration. Considering the intricate mechanism of the pathological process of CIRI, most drugs only work on one target. The neurovascular unit (NVU) puts forward the concept of neuroprotection from nerve protection to global stabilization. The NVU plays an important role in maintaining the brain microenvironment. This would promote neuronal survival and overall neurological recovery, which would likely lead to the reduction of mortality rate. Previous studies have shown that 4-methoxy benzyl alcohol (4-MA) ameliorated neurological score and cerebral infarct volume and reduced the concentration of Evans blue (EB) in brain tissue. In this research, we investigated the effects of 4-MA on NVU microenvironment improvement in rats impaired by middle cerebral artery occlusion/reperfusion (MCAO/R).

METHODS

First, we established a rat model of middle cerebral artery occlusion (MCAO) so as to use Western blot analysis, immunofluorescence and transmission electron microscopy (TEM) evaluating the NVU's protection of 4-MA. Then we established a primary cortical neuron model of oxygen glucose deprivation and re-oxygenation (OGD/R) with the objective of identifying whether 4-MA exhibited anti-oxidant and anti-apoptotic effects on neurons.

RESULTS

NVU ultra structural changes were improved by 4-MA. Immunofluorescence and western blot showed that 4-MA protected NVUs through enhancement of the expression of the symbolic neuronal proteins Microtubule Associated Protein-2(MAP-2), and attenuation of protein expression of Asy symbolic protein Glial Fibrillary Acidic Protein(GFAP). Furthermore, in the OGD/R model of I/R injury in vitro, 4-MA significantly increased Superoxide dismutase(SOD), Nitric Oxide(NO), B-cell lymphoma-2(Bcl-2), decreased Bcl-2-Associated X(Bax) and increased Bcl-2/Bax.

CONCLUSION

4-MA can play the role of anti-ischemic stroke drug by ameliorating the microenvironment of NVUs while its neuroprotective effects will contribute towards the inhibition of the antioxidant and anti-apoptotic activities.

Authors+Show Affiliations

Department of Pharmacology, Yunnan University of Chinese Medicine, Kunming 650500, China.Department of Pharmacology, Yunnan University of Chinese Medicine, Kunming 650500, China.Department of Pharmacology, Yunnan University of Chinese Medicine, Kunming 650500, China.Department of Pharmacology, Yunnan University of Chinese Medicine, Kunming 650500, China.Department of Pharmacology, Yunnan University of Chinese Medicine, Kunming 650500, China.Department of Pharmacology, Yunnan University of Chinese Medicine, Kunming 650500, China.Department of Pharmacology, Yunnan University of Chinese Medicine, Kunming 650500, China.Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming, 650500, China. Electronic address: yangynni@163.com.Department of Pharmacology, Yunnan University of Chinese Medicine, Kunming 650500, China. Electronic address: 1609627617@qq.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31548176

Citation

He, Fangyan, et al. "Protective Effect of 4-Methoxy Benzyl Alcohol On the Neurovascular Unit After Cerebral Ischemia Reperfusion Injury." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 118, 2019, p. 109260.
He F, Dai R, Zhou X, et al. Protective effect of 4-Methoxy benzyl alcohol on the neurovascular unit after cerebral ischemia reperfusion injury. Biomed Pharmacother. 2019;118:109260.
He, F., Dai, R., Zhou, X., Li, X., Song, X., Yan, H., Meng, Q., Yang, C., & Lin, Q. (2019). Protective effect of 4-Methoxy benzyl alcohol on the neurovascular unit after cerebral ischemia reperfusion injury. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 118, 109260. https://doi.org/10.1016/j.biopha.2019.109260
He F, et al. Protective Effect of 4-Methoxy Benzyl Alcohol On the Neurovascular Unit After Cerebral Ischemia Reperfusion Injury. Biomed Pharmacother. 2019;118:109260. PubMed PMID: 31548176.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effect of 4-Methoxy benzyl alcohol on the neurovascular unit after cerebral ischemia reperfusion injury. AU - He,Fangyan, AU - Dai,Rong, AU - Zhou,Xiaonan, AU - Li,Xiufang, AU - Song,Xuelan, AU - Yan,Hanwen, AU - Meng,Qingting, AU - Yang,Cui, AU - Lin,Qing, Y1 - 2019/08/29/ PY - 2019/05/30/received PY - 2019/07/20/revised PY - 2019/07/24/accepted PY - 2019/9/25/pubmed PY - 2020/2/14/medline PY - 2019/9/25/entrez KW - 4-Methoxy benzyl alcohol KW - Cerebral ischemia and reperfusion injury KW - Neurovascular unit KW - Oxygen glucose deprivation and re-oxygenation SP - 109260 EP - 109260 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 118 N2 - OBJECTIVE: Cerebral ischemia reperfusion injury (CIRI) is a major cause of ischemic stroke (IS) deterioration. Considering the intricate mechanism of the pathological process of CIRI, most drugs only work on one target. The neurovascular unit (NVU) puts forward the concept of neuroprotection from nerve protection to global stabilization. The NVU plays an important role in maintaining the brain microenvironment. This would promote neuronal survival and overall neurological recovery, which would likely lead to the reduction of mortality rate. Previous studies have shown that 4-methoxy benzyl alcohol (4-MA) ameliorated neurological score and cerebral infarct volume and reduced the concentration of Evans blue (EB) in brain tissue. In this research, we investigated the effects of 4-MA on NVU microenvironment improvement in rats impaired by middle cerebral artery occlusion/reperfusion (MCAO/R). METHODS: First, we established a rat model of middle cerebral artery occlusion (MCAO) so as to use Western blot analysis, immunofluorescence and transmission electron microscopy (TEM) evaluating the NVU's protection of 4-MA. Then we established a primary cortical neuron model of oxygen glucose deprivation and re-oxygenation (OGD/R) with the objective of identifying whether 4-MA exhibited anti-oxidant and anti-apoptotic effects on neurons. RESULTS: NVU ultra structural changes were improved by 4-MA. Immunofluorescence and western blot showed that 4-MA protected NVUs through enhancement of the expression of the symbolic neuronal proteins Microtubule Associated Protein-2(MAP-2), and attenuation of protein expression of Asy symbolic protein Glial Fibrillary Acidic Protein(GFAP). Furthermore, in the OGD/R model of I/R injury in vitro, 4-MA significantly increased Superoxide dismutase(SOD), Nitric Oxide(NO), B-cell lymphoma-2(Bcl-2), decreased Bcl-2-Associated X(Bax) and increased Bcl-2/Bax. CONCLUSION: 4-MA can play the role of anti-ischemic stroke drug by ameliorating the microenvironment of NVUs while its neuroprotective effects will contribute towards the inhibition of the antioxidant and anti-apoptotic activities. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/31548176/Protective_effect_of_4_Methoxy_benzyl_alcohol_on_the_neurovascular_unit_after_cerebral_ischemia_reperfusion_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(19)32512-0 DB - PRIME DP - Unbound Medicine ER -