The Role Of ERK In Focal Cerebral Ischemia And The Protective Effects Against Ischemic Brain Injury In Mouse

ObjectiveTo determine the role of extracellular signal-regulated kinase (ERK) 1 and 2during the focal cerebral ischemia in mouse.Materials and MethodsMale adult CD-I mice underwent left middle cerebral artery occlusion (MCAO)after introducing a nylon suture to the lumen. Surface cerebral blood flow(sCBF) was measured by laser Doppler flowmetry (LDF). ERK1 and ERK 2phosphorylation was detected by Western blot analysis andimmunohistochemistry.ResultsThe physiological data of the experiment mice after MCAO, including the meanartery blood pressure, the blood pH, the PaO2 and PaCO2, showed insignificantdifference compared with those before MCAO. The surface blood flow reducedto 10% and 20% after MCAO in the ischemic core and the surrounding areasrespectively. The activity of phosphorylated ERK1 and 2 (pERKl and pERK2)increased after 30 min of MCAO, peaked at 2 h and returned to basal level at 6 h.A large number of pERKl and pERK2 positive cells were observed in ischemicbasal ganglion and surrounding cortex after 30 min and 2 h of MCAO by theimmunohistochemical study. Double-labeled fluorescent staining identified thepERKl and pERK2 positive cells as neurons or astrocytes.ConclusionsIntroducing a suture into the middle cerebral artery can produce stable focalcerebral ischemia in mouse. Laser Doppler flowmetry is a reliable method tomeasure the instant blood flow and to confirm a successful cerebral ischemia.Activation of ERK 1 and ERK2 mainly occurs in the neurons and the astrocytes inthe ischemic basal ganglia and the surrounding cortex during the early stage ofcerebral ischemia.