Effects of extracellular signal-regulated kinase (ERK) on focal 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.
Department of Neurosurgery, Neurological Institute, Huashan Hospital, Fudan University, Shanghai 200040, China. zhiqiuwang@yahoo.com
Zhiqiu
Z
Wang
Xiancheng
X
Chen
Liangfu
L
Zhou
Duchu
D
Wu
Xiaoming
X
Che
Guoyuan
G
Yang
D000818:Animals; D001479:Basal Ganglia / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002070:Butadienes / Q000494:pharmacology; D002540:Cerebral Cortex / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation
D002070:Butadienes; D009570:Nitriles; C113580:U 0126; D020928:Mitogen-Activated Protein Kinases