Rho-Kinase inhibition decreases focal cerebral ischemia-induced glial activation in rats.
Background: Rho-kinase inhibition in a rat middle cerebral artery occlusion (MCAO) model is reported to improve neurological functions and decrease infarction size. Objective: The objective of this study is to investigate the underlying mechanisms of such improvement by evaluating the effects of Rho...
| Publicado en: | Journal of Central Nervous System Disease pp. 1 - 12 |
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| Autores principales: | , , , , , |
| Formato: | diagnostic images pictorial research tables/charts Journal Article |
| Publicado: |
Sage Publications Inc.
9/8/2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=158991774&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 158991774 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11795735 B3L8 jtl: Journal of Central Nervous System Disease issn: 11795735 maglogo: Y pubinfo: dt: 9/8/2022 pid: 344 pub: Sage Publications Inc. place: Thousand Oaks, California artinfo: ui: 158991774 158991774 158991774 10.1177/11795735221123910 158991774 ppf: 1 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Rho-Kinase inhibition decreases focal cerebral ischemia-induced glial activation in rats. aug: au: Sheikh, Abdullah Md Yano, Shozo Mitaki, Shingo Tabassum, Shatera Yamaguchi, Shuhei Nagai, Atsushi affil: Department of Laboratory Medicine, 175764 Shimane University Faculty of Medicine, Izumo, Japan sug: subj: Cerebral Ischemia Complications Glial Cells Pathology Phosphotransferases Animal Studies Rats Blotting, Western Magnetic Resonance Imaging Cell Migration Assays In Vitro Studies RNA, Messenger Analysis Analysis of Variance T-Tests Descriptive Statistics P-Value Data Analysis Software ab: Background: Rho-kinase inhibition in a rat middle cerebral artery occlusion (MCAO) model is reported to improve neurological functions and decrease infarction size. Objective: The objective of this study is to investigate the underlying mechanisms of such improvement by evaluating the effects of Rho-kinase inhibition on astrocytes and microglial accumulation and activation in this condition. Methods: Adult male Sprague-Dawley (SD) rats were used to generate the MCAO model, which received an I.P injection of a chemical Rho-kinase inhibitor (Fasudil- 5 mg/kg/day) or vehicle (PBS) for 2 and 4 days. Results: Fasudil treatment significantly decreased the stroke volumes and water content in the lesion areas, as revealed by MRI. Immunostaining and Western blotting results demonstrated that Fasudil significantly decreased the levels of Aquaporin-4, a water channel protein. The number of GFAP+ astrocytes and Iba-1+ macrophage/microglia was decreased in the lesion areas. Proinflammatory transcription factor NF-κB protein levels were decreased in the Fasudil group 2 days after MCAO. Also, proinflammatory mediators including TNF-α, IL-1β, and iNOS levels were decreased. In vitro migration study using a human microglial cell line (HMO6) confirmed the inhibitory effects of Fasudil on the process. Fasudil also decreased combined IL-1β and IFNγ-induced NF-κB nuclear translocation in HMO6. Moreover, Fasudil transiently decreased combined IL-1β and IFNγ-induced iNOS, TNFα, and IL-1β mRNA levels in HMO6. Conclusion: Our study demonstrates the inhibitory effects of Rho-kinase on NF-κB-mediated glial activation and cerebral edema, which might be a promising therapeutic target in acute cerebral ischemia conditions. pubtype: Academic Journal doctype: diagnostic images pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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