Activation of mitogen-activated protein kinases after permanent cerebral artery occlusion in mouse brain

The purpose of this study was to examine the activation, topographic distri bution, and cellular location of three mitogen-activated protein kinases (M APKs) after permanent middle cerebral artery occlusion (MCAO) in mice. Phos phorylated MAPKs expression in the ischemic region was quantified using Wes tern blot analysis and localized immunohistochemically using the diaminoben zide staining and double-labeled immunostaining. Extracellular signal-regul ated kinases and 2 (ERK1 and ERK2), p38 mitogen-activated protein (p38), an d c-Jun NH2-terminal kinase or stress-activated protein kinase (SAPK/JNK) w ere initially activated at 30 minutes, 10 minutes, and 5 minutes, respectiv ely, after focal cerebral ischemia. Peak expression represented a 2.7-fold, 3.7-fold. and 4.8-fold increase in each of these MAPKs, respectively. The immunohistochemical expressions of ERK1, ERK2, p38, and SAPK/JNK protein pa ralleled the Western blot analysis results. Double-labeled immunofluorescen t staining demonstrated that the neurons and astrocytes expressed ERK1, ERK 2, p38, and SAPK/JNK during the early time points after MCAO. The current r esults demonstrate that brain damage after ischemia rapidly triggers time-d ependent ERK1, ERK2, p38, and SAPK/JNK phosphorylation, and reveals that ne urons and astrocytes are involved in the activation of the MAPK pathway. Th is very early expression of MAPKs suggests that MAPKs may be closely involv ed in signal transduction during cerebral ischemia.