Rho-kinase inhibitor, fasudil, prevents neuronal apoptosis via the Akt activation and PTEN inactivation in the ischemic penumbra of rat brain.

Cellular and Molecular Neurobiology
Jianhua WuDongfang Wu

Abstract

Recently, some studies suggested that inhibition of Rho-kinase (ROCK) prevented cerebral ischemia injury through inhibiting inflammatory reaction, increasing cerebral blood flow, modulating the neuronal actin cytoskeleton polymerization, and preventing tau hyperphosphorylation and p25/CDK5 increase. However, there is little information regarding the effects of ROCK inhibitor on the neuronal apoptosis in ischemic brain injury. In this study, we determined whether ROCK inhibitor, fasudil, inhibited ischemic neuronal apoptosis through phosphatase and tensin homolog deleted on chromosome10 (PTEN)/Akt/signal pathway in vivo. Adult male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion. Rats received ROCK inhibitor, fasudil (10 mg/kg), at 30 min before middle cerebral artery occlusion. The infarct area, neuronal apoptosis and caspase-3 activity was significantly decreased by fasudil with improvement of neurological deterioration. However, the beneficial effects of fasudil were attenuated by the co-application of LY294002 (PI3K inhibitor). Fasudil maintained postischemic Akt activity at relatively proper level and decreased the augmentation of PTEN and ROCK activity in the penumbra area. Furthermore, fas...Continue Reading

References

Feb 5, 2000·Biochimica Et Biophysica Acta·F Vazquez, W R Sellers
Nov 18, 2000·Experimental Cell Research·M AmanoK Kaibuchi
Jul 13, 2001·The Journal of Biological Chemistry·G Schwartzbauer, J Robbins
Jul 18, 2001·Brain Research. Molecular Brain Research·H YaoH Uchimura
Dec 12, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·N NoshitaP H Chan
Dec 10, 2003·Oncogene·Thomas F FrankeChizuru Sugimoto
Apr 23, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ke NingQi Wan
Sep 25, 2004·Stroke; a Journal of Cerebral Circulation·Pak H Chan
Jan 20, 2005·The Journal of Cell Biology·Daniel R CroftMichael F Olson
Mar 29, 2005·Nature Cell Biology·Zhong LiDianqing Wu
Sep 6, 2005·Stroke; a Journal of Cerebral Circulation·Yoshiyuki RikitakeJames K Liao
Oct 21, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Heng ZhaoGary K Steinberg
Mar 16, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hidenori EndoPak H Chan
Sep 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jiang ChangRobert J Schwartz
Oct 13, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hwa Kyoung ShinCenk Ayata
Jan 16, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Shabaz A HamidGary F Baxter
Mar 10, 2007·Archivum Immunologiae Et Therapiae Experimentalis·Jianjian Shi, Lei Wei
Apr 14, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Teresa SanchezTimothy Hla
Jan 1, 2008·Apoptosis : an International Journal on Programmed Cell Death·Melanie van der HeijdenA B Johan Groeneveld
Sep 2, 2008·Brain : a Journal of Neurology·Véronique PlanchampPaul Lingor
Feb 3, 2009·Stroke; a Journal of Cerebral Circulation·Brad R S BroughtonChristopher G Sobey
Apr 27, 2011·Behavioral Neuroscience·John Fredy Castro-AlvarezGloria Patricia Cardona-Gómez

❮ Previous
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Citations

Nov 8, 2014·Glia·Ana I Rodriguez-PerezJose L Labandeira-Garcia
Jan 28, 2014·Annals of Clinical and Translational Neurology·Jeong Hyun LeeCenk Ayata
Sep 12, 2013·Neuroscience Letters·Guiyun CuiXinchun Ye
Jun 17, 2014·International Endodontic Journal·H Y PanT Hu
Feb 1, 2015·General and Comparative Endocrinology·Fangfang FangHang Xiao
May 26, 2016·Translational Stroke Research·Italo Linfante, Marilyn J Cipolla
Dec 9, 2016·The International Journal of Neuropsychopharmacology·Gonzalo García-RojoJenny L Fiedler
Apr 15, 2016·Stem Cells Translational Medicine·Jannette Rodriguez-PallaresJose L Labandeira-Garcia
Apr 22, 2017·Cardiovascular Research·Adrienn KrauszmanWolfgang M Kuebler
Mar 2, 2016·International Journal of Molecular Sciences·Hima Charika S AbeysingheCarli L Roulston
Jun 27, 2012·The Journal of Pharmacology and Experimental Therapeutics·Daniela ImpellizzeriSalvatore Cuzzocrea
Oct 1, 2015·Pharmacological Reviews·Gervaise Loirand
Apr 29, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shi YueYuan Zhai
Jan 23, 2020·Cells·Shalaka Mulherkar, Kimberley F Tolias
Jul 1, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Siu-Lung Chan, Marilyn J Cipolla
Mar 14, 2019·Current Pharmaceutical Design·Fakhra AminBilqees Bano
Dec 18, 2019·Cellular and Molecular Neurobiology·Guang-Hui XieJian-Hua Wu
Oct 6, 2020·Journal of Alzheimer's Disease : JAD·Rafael Andrés Posada-Duque, Gloria Patricia Cardona-Gómez
Oct 20, 2020·Frontiers in Physiology·Romain MenetAyman ElAli
Sep 29, 2020·British Journal of Pharmacology·Andrea Lopez-LopezAna Muñoz

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