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Remote limb ischemic postconditioning protects against neonatal hypoxic-ischemic brain injury in rat pups by the opioid receptor/Akt pathway.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Zhou, Yilin Fathali, Nancy Lekic, Tim Ostrowski, Robert P. Chen, Chunhua Martin, Robert J. Timnath Tang, Jiping Zhang, John H. |
| Copyright Year | 2011 |
| Abstract | BACKGROUND AND PURPOSE Remote ischemic postconditoning, a phenomenon in which brief ischemic stimuli of 1 organ protect another organ against an ischemic insult, has been demonstrated to protect the myocardium and adult brain in animal models. However, mediators of the protection and underlying mechanisms remain to be elucidated. In the present study, we tested the hypothesis that remote limb ischemic postconditioning applied immediately after hypoxia provides neuroprotection in a rat model of neonatal hypoxia-ischemia (HI) by mechanisms involving activation of the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway. METHODS HI was induced in postnatal Day 10 rat pups by unilateral carotid ligation and 2 hours of hypoxia. Limb ischemic postconditioning was induced by 4 conditioning cycles of 10 minutes of ischemia and reperfusion on both hind limbs immediately after HI. The opioid antagonist naloxone, phosphatidylinositol-3-kinase inhibitor wortmannin, or opioid agonist morphine was administered to determine underlying mechanisms. Infarct volume, brain atrophy, and neurological outcomes after HI were evaluated. Expression of phosphorylated Akt, Bax, and phosphorylated ERK1/2 was determined by Western blotting. RESULTS Limb ischemic postconditioning significantly reduced infarct volume at 48 hours and improved functional outcomes at 4 weeks after HI. Naloxone and wortmannin abrogated the postconditioning-mediated infarct-limiting effect. Morphine given immediately after hypoxia also decreased infarct volume. Furthermore, limb ischemic postconditioning recovered Akt activity and decreased Bax expression, whereas no differences in phosphorylated ERK1/2expression were observed. CONCLUSIONS Limb ischemic postconditioning protects against neonatal HI brain injury in rats by activating the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway. |
| Starting Page | A467 |
| Ending Page | A467 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://stroke.ahajournals.org/content/strokeaha/42/2/439.full.pdf?download=true |
| Alternate Webpage(s) | http://stroke.ahajournals.org/content/strokeaha/early/2010/12/23/STROKEAHA.110.592162.full.pdf |
| PubMed reference number | 21183744v1 |
| Alternate Webpage(s) | https://doi.org/10.1161/STROKEAHA.110.592162 |
| DOI | 10.1161/strokeaha.110.592162 |
| Journal | Stroke |
| Volume Number | 42 |
| Issue Number | 2 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 1-Phosphatidylinositol 3-Kinase Animal Model Atrophic Brain Injuries Cerebral atrophy Conditioning (Psychology) Hypoxia-Ischemia, Brain Hypoxic-Ischemic Encephalopathy Infarction Ligation Limb structure Morphine Myocardial Ischemia Myocardium Naloxone Narcotic Antagonists Neuroprotection Opioid Receptor Proto-Oncogene Proteins c-akt Reperfusion Therapy Signal Transduction Pathways Transient Ischemic Attack Western Blot Western Blotting neonatal hypoxia wortmannin |
| Content Type | Text |
| Resource Type | Article |
