Reduced cerebral injury in CRH-R1 deficient mice after focal ischemia: A potential link to microglia and atrocytes that express CRH-R1

Susan L. Stevens, Tatyana E. Shaw, Emily Dykhuizen, Nikola S. Lessov, Jennifer K. Hill, Wolfgang Wurst, Mary P. Stenzel-Poore

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Corticotropin releasing hormone (CRH) and its family of related peptides are involved in regulating physiologic responses to multiple stressors, including stroke. Although CRH has been implicated in the exacerbation of injury after stroke, the mechanism remains unclear. After ischemia, both excitotoxic damage and inflammation contribute to the pathology of stroke. CRH is known to potentiate excitotoxic damage in the brain and has been shown to modulate inflammatory responses in the periphery. Here the present authors examine the relative contribution of the two known CRH receptors, CRH-R1 and CRH-R2, to ischemic injury using CRH receptor knockout mice. These results implicate CRH-R1 as the primary mediator of ischemic injury in this mouse model of stroke. In addition, the authors examine a potential role for CRH in inflammatory injury after stroke by identifying functional CRH receptors on astrocytes and microglia, which are cells that are known to be involved in brain inflammation. By single cell PCR, the authors show that microglia and astrocytes express mRNA for both CRH-R1 and CRH-R2. However, CRH-R1 is the primary mediator of cAMP accumulation in response to CRH peptides in these cells. The authors suggest that astrocytes and microglia are cellular targets of CRH, which could serve as a link between CRH and inflammatory responses in ischemic injury via CRH-R1.

Original languageEnglish (US)
Pages (from-to)1151-1159
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume23
Issue number10
DOIs
StatePublished - Oct 1 2003

Keywords

  • Astrocytes
  • CRH
  • CRH-R1
  • Ischemia
  • Microglia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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