This Article Full Text Full Text (PDF) All Versions of this Article: 37/4/1094    most recent 01.STR.0000206444.29930.18v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, J. Articles by Xia, Y. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Articles by Xia, Y. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB GLUTAMIC ACID HYDROCHLORIDE NALTREXONE

(Stroke. 2006;37:1094.)
© 2006 American Heart Association, Inc.

Original Contributions

Rapid Hypoxia Preconditioning Protects Cortical Neurons From Glutamate Toxicity Through -Opioid Receptor

Junhui Zhang, MD; Hong Qian, MD; Peng Zhao, PhD; Soon-Sun Hong, PhD Ying Xia, MD, PhD

From the Department of Pediatrics, Yale University School of Medicine, New Haven, Conn.

Correspondence to Ying Xia, MD, PhD, Yale University School of Medicine, Department of Pediatrics, New Haven, CT 06520. E-mail ying.xia{at}yale.edu

Background and Purpose— Hypoxia preconditioning (HPC), rapid or delayed, has been reported to induce neuroprotection against subsequent severe stress. Because -opioid receptor (DOR) plays an important role in delayed HPC-induced neuroprotection against severe hypoxic injury, we asked whether DOR is also involved in the rapid HPC-induced neuroprotection.

Methods— Cultured rat cortical neurons at culture days 8 to 9 were exposed to a short-term hypoxia (1% O₂ for 30 minutes) to induce HPC followed by 30-minute normoxia before exposing to glutamate toxicity (100 µmol/L; 4 hours). Neuronal viability was assessed by lactate dehydrogenase leakage and morphological assessment. Protein and mRNA levels of DOR were detected by receptor binding and RT-PCR, respectively. Naltrindole was used to block DOR. Developmental changes in NMDA receptor expression was measured by Western blots.

Results— HPC significantly reduced the glutamate-induced neuronal injury. Receptor binding showed that HPC increased DADLE (a DOR ligand) binding density in the cultured cortical neurons by >90% over control level (P<0.05), although RT-PCR did not detect any appreciable change in DOR mRNA. DOR inhibition with naltrindole had no effect on neuronal injury and completely abolished the HPC-induced neuroprotection. In contrast to HPC-induced increase in DADLE binding density, prolonged hypoxia caused severe neuronal injury with a significant decrease in DADLE binding density and DOR mRNA level.

Conclusions— DOR is involved in neuroprotection induced by rapid HPC in cortical neurons.

Key Words: cerebral cortex • hypoxia • neurons • neuroprotection • receptors, opioid

This article has been cited by other articles:

				R. Meller The Role of the Ubiquitin Proteasome System in Ischemia and Ischemic Tolerance Neuroscientist, June 1, 2009; 15(3): 243 - 260. [Abstract] [PDF]

				D. Chao, A. Bazzy-Asaad, G. Balboni, S. Salvadori, and Y. Xia Activation of DOR Attenuates Anoxic K+ Derangement via Inhibition of Na+ Entry in Mouse Cortex Cereb Cortex, September 1, 2008; 18(9): 2217 - 2227. [Abstract] [Full Text] [PDF]