Reduced cerebral injury in CRH-R1 deficient mice after focal ischemia: a potential link to microglia and atrocytes that express CRH-R1.
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.
Stevens
Susan L
SL
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon 97239, USA.
Shaw
Tatyana E
TE
Dykhuizen
Emily
E
Lessov
Nikola S
NS
Hill
Jennifer K
JK
Wurst
Wolfgang
W
Stenzel-Poore
Mary P
MP
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017628:Microglia / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D000242:Cyclic AMP