Neuroprotective Effects of Opioid-Like Hibernation Factors in Cerebral Ischemia
Abstract
We have shown that infusions of opioid-like hibernation factors can provide ischemic protection in vivo and in vitro. in a mouse cerebral ischemia model, we showed a marked reduction in cerebral infarct volume and behavioral deficits when Deltophins-A, D and Dermorphin-H were infused 1 hr after middle cerebral artery occlusion. Using mice deficient in either neuronal (nNOS), inducible (iNOS) or endothelial (eNOS) nitric oxide synthase, we showed that only endothelial NOS plays a key role in cerebral ischemic protection We found that Deltorphin-D inhibited nitric oxide (NO) release in a dose dependent manner when mouse N9 microglial cells were activated by lipopolysacciliaride (LPS) and interferon-gamma, giving further evidence that the neuroprotective effect of these delta opioids may include their ability to retard or block the release of NO and reactive oxygen species which occur in ischemic processes such as hemorrhagic shock, myocardial infarction, and stroke. Most recently, we showed that Deltorphin-D increased blood pressure and enhances 6 hr survival of rats undergoing hemorrhagic shock without concomitant fluid resuscitation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2004
- Accession Number
- ADA424443
Entities
People
- Peter R. Oeltgen
Organizations
- University of Kentucky