Reduced acute brain injury in PGE2 EP3 receptor-deficient mice after cerebral ischemia

Sofiyan Saleem, Yun Tai Kim, Takayuki Maruyama, Shuh Narumiya, Sylvain Doré

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Ischemic stroke is one of the leading causes of mortality and morbidity in humans. During brain ischemia and the subsequent reperfusion that occurs with stroke, the generation of the so-called "proinflammatory" prostaglandin E2 (PGE2) increases significantly. Therefore, interest is growing regarding the differential functions of the individual PGE2 receptors (EP1-4) and their relative contribution to brain damage following ischemic and inflammatory stimuli. Here, we address the contribution of the EP3 receptor in dictating early outcomes after transient cerebral ischemia. An oxygen-glucose deprivation (OGD)-induced in vitro model of brain ischemia was used in mouse hippocampal slice cultures. For transient ischemia, the right middle cerebral artery (MCA) of wildtype (WT) and EP3 knockout (EP3-/-) C57BL/6 male mice was occluded for 90 min and reperfused for 48 or 96 h, after which neurobehavioral scores and infarct volumes were determined. Mean arterial blood pressure, pH, blood gases (PaO2 and PaCO2), cerebral blood flow, and body temperature were also determined before and during ischemia and reperfusion. OGD-induced cell death was significantly lower in brain slice cultures of EP3-/- mice than in those of WT mice. EP3-/- mice that underwent transient ischemia had significantly smaller infarct volumes than did WT mice at 48 h, but this difference was not sustained at 96 h. Neurological score deficits correlated with infarct volume, but no significant differences in the physiological parameters monitored were detected between the two genotypes. The results further support a role for EP3 receptors in contributing to acute ischemic stroke, but EP3 is not likely the sole contributor to the long-term detrimental consequences of PGE2.

Original languageEnglish (US)
Pages (from-to)87-93
Number of pages7
JournalJournal of Neuroimmunology
Volume208
Issue number1-2
DOIs
StatePublished - Mar 31 2009
Externally publishedYes

Keywords

  • EP3 receptor
  • Focal cerebral ischemia
  • Oxygen-glucose deprivation
  • Prostanoids

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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