Cerebrovascular Endothelin Receptor Upregulation in Cerebral Ischemia

Lars      Edvinsson

Abstract

Stroke is a serious neurological disease and the third leading cause of death in the western world. In roughly 15 % of the cases, the cause is due to an intracranial haemorrhage, and the remaining 85 % represent ischemic strokes. Ischemic stroke is caused by the occlusion of a cerebral artery either by an embolus or by local thrombosis. Several studies have shown an involvement of the endothelin system in ischemic stroke. This review aims to examine the alterations of vascular endothelin receptor expression in ischemic stroke. Furthermore, studies of the intracellular signalling pathways leading to the enhanced expression of vascular endothelin receptors show that both protein kinase C (PKC) and mitogen activating protein kinase (MAPK) play important roles. The results from this work provide new perspectives on the pathophysiology of ischemic stroke, and give a possible explanation to the beneficial effects of treatment with PKC and MAPK inhibitors to limit the infarct volume.

Keywords: Cerebrovascular Endothelin Receptor, Cerebral Ischemia, neurological disease, Ischemic stroke, intracranial haemorrhage, protein kinase C (PKC), MAPK inhibitors

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