Late cerebral ischaemia after subarachnoid haemorrhage: is cerebrovascular receptor upregulation the mechanism behind?

L Edvinsson, G K Povlsen

19 Citations (Scopus)

Abstract

Late cerebral ischaemia after subarachnoid haemorrhage (SAH) carries high morbidity and mortality because of reduced cerebral blood flow (CBF) and subsequent cerebral ischaemia. This is associated with upregulation of contractile receptors in cerebral artery smooth muscles via the activation of intracellular signalling. In addition, delayed cerebral ischaemia after SAH is associated with inflammation and disruption of the blood-brain barrier (BBB). This article reviews recent evidence concerning the roles of vasoconstrictor receptor upregulation, inflammation and BBB breakdown in delayed cerebral ischaemia after SAH. In addition, recent studies investigating the role of various intracellular signalling pathways in these processes and the possibilities of targeting signalling components in SAH treatment are discussed. Studies using a rat SAH model have demonstrated that cerebral arteries increase their sensitivity to endogenous agonists such as ET-1 and 5-HT by increasing their smooth muscle expression of receptors for these after SAH. This is associated with reduced CBF and neurological deficits. A number of signal transduction components mediating this receptor upregulation have been identified, including the MEK-ERK1/2 pathway. Inhibition of MEK-ERK1/2 signalling has been shown to prevent cerebrovascular receptor upregulation and normalize CBF and neurological function after SAH in rats. At the same time, in rat SAH, certain cytokines and BBB-regulating proteins are upregulated in cerebral artery smooth muscles and treatment with MEK-ERK1/2 inhibitors prevents the induction of these proteins. Thus, inhibitors of MEK-ERK1/2 signalling exert multimodal beneficial effects in SAH.
Original languageEnglish
JournalActa Physiologica
Volume203
Issue number1
Pages (from-to)209-24
Number of pages16
ISSN1748-1708
DOIs
Publication statusPublished - 2011

Keywords

  • Animals
  • Brain Ischemia
  • Cerebrovascular Circulation
  • Humans
  • Receptors, Endothelin
  • Signal Transduction
  • Subarachnoid Hemorrhage
  • Up-Regulation
  • Vasoconstriction

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