OBJECTIVE: To determine the role of extracellular signal-regulated kinase (ERK)1/2 during focal cerebral ischemia. METHODS: Left middle cerebral artery occlusion (MCAO) was undergone after the introduction of a nylon suture to the left internal carotid artery in 70 male adult CD-1 mice. ERK 1/2 phosphorylation was detected using Western blot analysis, and the morphological feature was determined by immunohistochemistry. An ERK pathway inhibitor, 1,4-diamino-2,3-dicyano-1,4-bis[2-amino-phenylthio] butadiene (U0126), was administered intravenously 20 minutes before MCAO, and the neurological deficit levels and the infarct volumes were measured 24 hours after MCAO. RESULTS: Phosphorylated ERK 1/2 (pERK 1/2) activity increased after 30 minutes of MCAO and peaked at 2 hours. The immunohistochemical study displayed a large number of pERK 1/2 positive cells in the ischemic basal ganglion and surrounding cortex. Double-labeled fluorescent staining identified the pERK1/2 positive cells as neurons or astrocytes. In U0126 treated mice which had undergone 24 hours of MCAO, the neurological deficit levels and the infarct volumes were 44.6% and 45.8% respectively, less than those of the control mice. CONCLUSIONS: ERK plays an important role in focal cerebral ischemia and inhibition of the ERK pathway can help protect against ischemic brain injury, which may provide a therapeutic approach for cerebral ischemia.
OBJECTIVE: To determine the role of extracellular signal-regulated kinase (ERK)1/2 during focal cerebral ischemia. METHODS:Left middle cerebral artery occlusion (MCAO) was undergone after the introduction of a nylon suture to the left internal carotid artery in 70 male adult CD-1 mice. ERK 1/2 phosphorylation was detected using Western blot analysis, and the morphological feature was determined by immunohistochemistry. An ERK pathway inhibitor, 1,4-diamino-2,3-dicyano-1,4-bis[2-amino-phenylthio] butadiene (U0126), was administered intravenously 20 minutes before MCAO, and the neurological deficit levels and the infarct volumes were measured 24 hours after MCAO. RESULTS: Phosphorylated ERK 1/2 (pERK 1/2) activity increased after 30 minutes of MCAO and peaked at 2 hours. The immunohistochemical study displayed a large number of pERK 1/2 positive cells in the ischemic basal ganglion and surrounding cortex. Double-labeled fluorescent staining identified the pERK1/2 positive cells as neurons or astrocytes. In U0126 treated mice which had undergone 24 hours of MCAO, the neurological deficit levels and the infarct volumes were 44.6% and 45.8% respectively, less than those of the control mice. CONCLUSIONS:ERK plays an important role in focal cerebral ischemia and inhibition of the ERK pathway can help protect against ischemic brain injury, which may provide a therapeutic approach for cerebral ischemia.
Authors: Maria Kovalska; Libusa Kovalska; Martina Pavlikova; Maria Janickova; Katarina Mikuskova; Marian Adamkov; Peter Kaplan; Zuzana Tatarkova; Jan Lehotsky Journal: Neurochem Res Date: 2012-03-20 Impact factor: 3.996
Authors: Chandramohan Wakade; Mohammad M Khan; Liesl M De Sevilla; Quan-Guang Zhang; Virendra B Mahesh; Darrell W Brann Journal: Endocrinology Date: 2007-09-27 Impact factor: 4.736
Authors: Dennis Y Chuang; Jiankun Cui; Agnes Simonyi; Victoria A Engel; Shanyan Chen; Kevin L Fritsche; Andrew L Thomas; Wendy L Applequist; William R Folk; Dennis B Lubahn; Albert Y Sun; Grace Y Sun; Zezong Gu Journal: ASN Neuro Date: 2014-10-16 Impact factor: 4.146