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Neuroprotective effects of matrix metalloproteinases in cerebral ischemic rats by promoting activation and migration of astrocytes and microglia.
Brain Res Bull. 2019 03; 146:136-142.BR

Abstract

Matrix metalloproteinases (MMPs) cleave almost all components of the extracellular matrix (ECM) and cause acute neurovascular disruption and parenchymal destruction. Previously, MMPs inhibition was considered to be a therapeutic strategy in early stages of ischemia. This study was designed to investigate whether early MMPs inhibition could promote the recovery of cerebral ischemia. Male Sprague-Dawley rats underwent right middle cerebral artery occlusion (MCAO) for 1 h and reperfusion. The rats were divided into three groups: sham + vehicle (S + V) group, MCAO + vehicle (M + V) group, and MCAO + GM6001 (M + G) group. Infarct volume was assessed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, and the expression of GFAP, IBA1, p-ERK, ERK, and MMP9 were evaluated by Western blot and immunofluorescence staining on 1, 4, 7, and 14 days after MCAO. Neuronal apoptosis was assessed by Fluoro-Jade C staining. The results showed that MMPs inhibition significantly increased the infarct volume and the expressions of GFAP and IBA1 in the M + V group were much higher than those in the M + G group; whereas the expression of p-ERK was upregulated in both the M + V and M + G groups. These findings suggest that MMPs promote the activation and migration of astrocytes and microglia to form protected zone in the penumbra and lessen the infarct volume after cerebral ischemic stroke.

Authors+Show Affiliations

Department of Human Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China.Department of Human Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China.Department of Human Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China.Department of Human Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China. Electronic address: Hpli@cmu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30445183

Citation

Zhang, Xu, et al. "Neuroprotective Effects of Matrix Metalloproteinases in Cerebral Ischemic Rats By Promoting Activation and Migration of Astrocytes and Microglia." Brain Research Bulletin, vol. 146, 2019, pp. 136-142.
Zhang X, Zhao HH, Li D, et al. Neuroprotective effects of matrix metalloproteinases in cerebral ischemic rats by promoting activation and migration of astrocytes and microglia. Brain Res Bull. 2019;146:136-142.
Zhang, X., Zhao, H. H., Li, D., & Li, H. P. (2019). Neuroprotective effects of matrix metalloproteinases in cerebral ischemic rats by promoting activation and migration of astrocytes and microglia. Brain Research Bulletin, 146, 136-142. https://doi.org/10.1016/j.brainresbull.2018.11.003
Zhang X, et al. Neuroprotective Effects of Matrix Metalloproteinases in Cerebral Ischemic Rats By Promoting Activation and Migration of Astrocytes and Microglia. Brain Res Bull. 2019;146:136-142. PubMed PMID: 30445183.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective effects of matrix metalloproteinases in cerebral ischemic rats by promoting activation and migration of astrocytes and microglia. AU - Zhang,Xu, AU - Zhao,Hai-Hua, AU - Li,Dan, AU - Li,Hong-Peng, Y1 - 2018/11/13/ PY - 2018/08/28/received PY - 2018/10/26/revised PY - 2018/11/09/accepted PY - 2018/11/18/pubmed PY - 2020/3/11/medline PY - 2018/11/17/entrez KW - Astrocyte KW - Cerebral ischemia KW - Matrix metalloproteinase KW - Microglia KW - p-ERK SP - 136 EP - 142 JF - Brain research bulletin JO - Brain Res. Bull. VL - 146 N2 - Matrix metalloproteinases (MMPs) cleave almost all components of the extracellular matrix (ECM) and cause acute neurovascular disruption and parenchymal destruction. Previously, MMPs inhibition was considered to be a therapeutic strategy in early stages of ischemia. This study was designed to investigate whether early MMPs inhibition could promote the recovery of cerebral ischemia. Male Sprague-Dawley rats underwent right middle cerebral artery occlusion (MCAO) for 1 h and reperfusion. The rats were divided into three groups: sham + vehicle (S + V) group, MCAO + vehicle (M + V) group, and MCAO + GM6001 (M + G) group. Infarct volume was assessed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, and the expression of GFAP, IBA1, p-ERK, ERK, and MMP9 were evaluated by Western blot and immunofluorescence staining on 1, 4, 7, and 14 days after MCAO. Neuronal apoptosis was assessed by Fluoro-Jade C staining. The results showed that MMPs inhibition significantly increased the infarct volume and the expressions of GFAP and IBA1 in the M + V group were much higher than those in the M + G group; whereas the expression of p-ERK was upregulated in both the M + V and M + G groups. These findings suggest that MMPs promote the activation and migration of astrocytes and microglia to form protected zone in the penumbra and lessen the infarct volume after cerebral ischemic stroke. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/30445183/Neuroprotective_effects_of_matrix_metalloproteinases_in_cerebral_ischemic_rats_by_promoting_activation_and_migration_of_astrocytes_and_microglia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(18)30663-4 DB - PRIME DP - Unbound Medicine ER -