Intracerebral hemorrhage injury mechanisms: Glutamate neurotoxicity, thrombin, and Src

Research output: Chapter in Book/Report/Conference proceedingChapter

37 Scopus citations

Abstract

The mechanisms accounting for variable increases in blood flow and seizures following intracerebral hemorrhage (ICH) are unknown. Local cerebral glucose utilization (LCGU) studies performed to address this issue demonstrate increased LCGU within hours around an ICH that is blocked by NMDA and AMPA glutamate receptor antagonists. Local injections of NMDA or AMPA increased LCGU whereas glutamate did not, suggesting an ICH effect on glutamate uptake or glutamate receptors. To address these possibilities, we performed genomic studies of brain following ICH. Among the many regulated genes, an Src family member, Lyn, increased expression over 20-fold. This was important, since Src is known to phosphorylate NMDA receptors and augment their function, and thrombin is known to activate PARs that activate Src. This prompted us to study the Src antagonist, PP2. PP2 decreased LCGU and cell death around ICH and improved behavioral function following ICH. This data leads us to suggest our hypothesis, that ICH, possibly via thrombin activation of protease-activated receptors, activates Src that phosphorylates NMDA receptors and other proteins that mediate injury after ICH.

Original languageEnglish (US)
Title of host publicationCerebral Hemorrhage
PublisherSpringer-Verlag Wien
Pages43-46
Number of pages4
Edition105
ISBN (Print)9783211094686
DOIs
StatePublished - Jan 1 2008

Publication series

NameActa Neurochirurgica, Supplementum
Number105
ISSN (Print)0065-1419

Keywords

  • Excitatory amino acids
  • Glutamate
  • Intracerebral hemorrhage
  • Src
  • Thrombin

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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    Sharp, F. R., Liu, D., Zhan, X., & Ander, B. (2008). Intracerebral hemorrhage injury mechanisms: Glutamate neurotoxicity, thrombin, and Src. In Cerebral Hemorrhage (105 ed., pp. 43-46). (Acta Neurochirurgica, Supplementum; No. 105). Springer-Verlag Wien. https://doi.org/10.1007/978-3-211-09469-3_9