Current perspective on the role of the thrombin receptor in cerebral vasospasm after subarachnoid hemorrhage

Katsuya Hirano, Mayumi Hirano

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Cerebral vasospasm is a persistent arterial narrowing typically observed during the 3 - 14 days after subarachnoid hemorrhage (SAH). Vasospasm is frequently associated with schemic neurological deficits or even death, resulting in a poor prognosis for patients with SAH. However, the mechanism underlying cerebral vasospasm remains elusive, and no effective therapeutic strategies have been established. A large amount of thrombin is produced during SAH. Recent investigations have uncovered a key role of the thrombin receptor in the pathogenesis of cerebral vasospasm. Thrombin has little contractile effect in the normal cerebral artery, but it induces an enhanced and prolonged contraction after SAH, owing to the up-regulation of thrombin receptor PAR1 (proteinase-activated receptor 1) and the impairment of receptor desensitization in arterial smooth muscle. Thrombin-mediated activation of PAR1 is an irreversible process, as it is initiated by the proteolytic removal of the N-terminal region. Since the mechanism of receptor desensitization is impaired after SAH, the thrombin-induced contraction irreversibly persists even after terminating thrombin stimulation. Intrathecal administration of a PAR1 antagonist prevents the PAR1 up-regulation and the increased reactivity to thrombin. PAR1 is suggested to play a key role in cerebral vasospasm and may be useful as a therapeutic target for prevention and treatment of cerebral vasospasm.

Original languageEnglish
Pages (from-to)127-133
Number of pages7
JournalJournal of Pharmacological Sciences
Volume114
Issue number2
DOIs
Publication statusPublished - Nov 22 2010

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Thrombin Receptors
Intracranial Vasospasm
PAR-1 Receptor
Subarachnoid Hemorrhage
Thrombin
Up-Regulation
Cerebral Arteries
Smooth Muscle
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Current perspective on the role of the thrombin receptor in cerebral vasospasm after subarachnoid hemorrhage. / Hirano, Katsuya; Hirano, Mayumi.

In: Journal of Pharmacological Sciences, Vol. 114, No. 2, 22.11.2010, p. 127-133.

Research output: Contribution to journalArticle

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