Abstract |
The contribution of corticotropin-releasing hormone (CRH) in the modulation of ischemia-induced cell death in vivo remains unclear. We characterized the impact of pre-ischemic administration of CRH (0, 0.1, 1, 5 microg, i.c.v., 15 min prior to vessel occlusion) on neuronal damage following global ischemia in rats. The injection of 5 microg CRH led to a 37% increase in CA1 neuronal survival compared to vehicle-treated ischemic animals, while pre-treatment with alpha-helical CRH (9-41) abolished this neuronal protection. A second objective aimed to determine whether CRH protection is maintained over weeks when the peptide is administered at remote time intervals following ischemia. Compared to vehicle-treated ischemic animals, administration of CRH 8h following global ischemia led to a 61% increase in CA1 neuronal survival observed 30 days post- ischemia. Neuronal protection translated into significant improvement of ischemia-induced spatial memory deficits in the radial maze. Finally, our findings demonstrated that selective blockade of kappa- and delta-opioid receptors (using nor-binaltorphimine and naltrindole, respectively) prior to CRH administration significantly reduced CA1 neuronal protection. These findings represent the first demonstration of enhanced neuronal survival following in vivo CRH administration in a global model of ischemia in rats. They also support the idea that CRH-induced neuroprotection involves opioid receptors activation.
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Authors | Charlaine Charron, Sabrina Fréchette, Geneviève Proulx, Hélène Plamondon |
Journal | Behavioural brain research
(Behav Brain Res)
Vol. 188
Issue 1
Pg. 125-35
(Mar 17 2008)
ISSN: 0166-4328 [Print] Netherlands |
PMID | 18055027
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Neuroprotective Agents
- Receptors, Opioid, delta
- Receptors, Opioid, kappa
- Corticotropin-Releasing Hormone
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Topics |
- Analysis of Variance
- Animals
- Brain Ischemia
(metabolism, pathology)
- Cell Death
(physiology)
- Corticotropin-Releasing Hormone
(administration & dosage, metabolism)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Hippocampus
(metabolism, pathology)
- Injections, Intraventricular
- Male
- Maze Learning
(physiology)
- Nerve Degeneration
(metabolism, prevention & control)
- Neurons
(metabolism, pathology)
- Neuroprotective Agents
(administration & dosage, metabolism)
- Rats
- Rats, Wistar
- Receptors, Opioid, delta
(antagonists & inhibitors, metabolism)
- Receptors, Opioid, kappa
(antagonists & inhibitors, metabolism)
- Time Factors
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