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Reduced cerebral injury in CRH-R1 deficient mice after focal ischemia: a potential link to microglia and atrocytes that express CRH-R1
- Source :
- Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 23(10)
- Publication Year :
- 2003
-
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.
- Subjects :
- endocrine system
medicine.medical_specialty
Ischemia
Gene Expression
Inflammation
Receptors, Corticotropin-Releasing Hormone
030218 nuclear medicine & medical imaging
Brain Ischemia
03 medical and health sciences
Corticotropin-releasing hormone
Mice
0302 clinical medicine
Mediator
Internal medicine
polycyclic compounds
medicine
Cyclic AMP
Animals
RNA, Messenger
Receptor
Microglia
business.industry
Cerebral Infarction
medicine.disease
Mice, Mutant Strains
Mice, Inbred C57BL
medicine.anatomical_structure
Endocrinology
nervous system
Neurology
Astrocytes
Knockout mouse
Neurology (clinical)
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Neuroscience
hormones, hormone substitutes, and hormone antagonists
030217 neurology & neurosurgery
Astrocyte
Subjects
Details
- ISSN :
- 0271678X
- Volume :
- 23
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
- Accession number :
- edsair.doi.dedup.....78ee5296eacd44caa7f58c53c14bd092