Dynamic changes in protein kinase expression in cerebral arteries after stroke

Abstract

Objective The pathogenesis of cerebral ischemia after subarachnoid hemorrhage (SAH) still remains elusive. Previous studies have demonstrated an upregulation of endothelin type B (ETB) and 5-hydroxytryptamine type 1B (5-HT1B) receptors in cerebral arteries following experimental SAH. It has been suggested that intracellular pathways containing protein kinase C (PKC) and mitogen activated protein kinase (MAPK) are responsible for this upregulation. The aim of this study was to examine the involvement of PKC and MAPK in the pathophysiology of stroke. Furthermore, we wanted to examine the time course of the kinase activation. Methods SAH was induced by injecting 250 μl blood into the prechiasmatic cistern. The expression of different types of MAPK and PKC isotypes in cerebral arteries were examined at 1, 3, 6, 12, 24 and 48 hours after SAH by use of Western blot. Results Among the 8 investigated PKC isoforms only PKCdelta, and PKCeta protein levels were activated at 1 hrs and remained elevated after SAH. The same pattern was seen for ERK1/2 while PKCalpha, JNK and p38 were increased only at 48hrs after SAH. Conclusion The results indicate that MAPK and PKC pathways play an important role in the pathogenesis of cerebral ischemia after SAH. The study was supported by the Swedish Heart-Lung Foundation, the Swedish Research Council, the Danish Research Council and the Augustinus Foundation (Denmark)