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NMMHC IIA Regulates Cerebral Ischemia‐Induced Blood‐Brain Barrier Dysfunction by Modulating MAPKs and LATS1/2/YAP signaling pathways
Author(s) -
Gong Shuaishuai,
Li Fang,
Kou Junping
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.496.57
Subject(s) - occludin , blood–brain barrier , ischemia , in vivo , central nervous system , pharmacology , tight junction , microbiology and biotechnology , medicine , chemistry , biology
Although blood–brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial proteins that control BBB function are poorly defined. Based on previous studies, the underlying mechanisms and function of NMMHC IIA‐ mediated BBB dysfunction induced by ischemic stroke were investigated using the NMMHC IIA inhibitor blebbistatin in middle cerebral artery occlusion/reperfusion (MCAO/R)‐injured mice and oxygen‐glucose deprivation/reoxygenation (OGD/R)‐injured mouse brain microvascular endothelial cells (bEnd.3). The results in vivo suggested that blebbistatin (10 mg/kg) could significantly decrease infarct volume, brain water content and Neurological deficits, and increase the cerebral blood flow. In addition, blebbistatin could ameliorate histopathological damage and reduce the BBB leakage following ischemic stroke. Besides, blebbistatin also could up‐regulate the expression of ZO‐1 and Occludin, inhibit the MMP‐2 and MMP‐9 expressions, and modulate the MAPKs and LATS1/2/YAP signaling pathways in ischemic stroke‐induced mice. Meanwhile, the in vitro results demonstrated that pretreatment with blebbistatin (1μM) could significantly recover the cell viability, increase the TEER value and inhibit the fluorescein sodium permeability in OGD/R‐induced bEnd.3 cells. In addition, pretreatment with blebbistatin (1μM) also could up‐regulate the expression of ZO‐1 and Occludin, inhibit the MMP‐2 and MMP‐9 expressions, and modulate the MAPKs and LATS1/2/YAP signaling pathways in bEnd.3 cells subjected to OGD/R. The in vitro results were consistent with the results of in vivo. All these findings indicated that the function of NMMHC IIA protein might be the key target and pivotal link involved in regulating ischemic stroke‐induced BBB dysfunction. Support or Funding Information the National Natural Science Foundation of China (Grant No.81773971)Blebbistatin could significantly decrease infarct volumeBlebbistatin could significantly increase the cerebral blood flowBlebbistatin could significantly reduce the BBB leakage following ischemic strokeInhibition of NMMHC IIA attenuates stress fiber formation in cerebral ischemia and reperfusion injurypretreatment with blebbistatin (1μM) could LATS1/2/YAP signaling pathway in bEnd.3 cells subjected to OGD/R.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .