Rapid hypoxia preconditioning protects cortical neurons from glutamate toxicity through δ-opioid receptor

• Published in: Stroke (1970) Vol. 37; no. 4; pp. 1094 - 1099
• Main Authors: JUNHUI ZHANG, HONG QIAN, PENG ZHAO, HONG, Soon-Sun, YING XIA
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.04.2006
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Cellular Senescence; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Enkephalin, Leucine-2-Alanine - metabolism; General and cellular metabolism. Vitamins; Glutamic Acid - poisoning; Hypoxia - physiopathology; Ischemic Preconditioning; L-Lactate Dehydrogenase - metabolism; Medical sciences; N-Methylaspartate - metabolism; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Neurology; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Rats; Receptors, Opioid, delta - antagonists & inhibitors; Receptors, Opioid, delta - genetics; Receptors, Opioid, delta - metabolism; RNA, Messenger - metabolism; Time Factors; Up-Regulation; Vascular diseases and vascular malformations of the nervous system; Stroke; Cerebral cortex; Oxygen; Nervous system diseases; receptors; Toxicity; Opioid receptor; opioid; Cardiovascular disease; Glutamate receptor; δ Opioid receptor; neurons; Cerebral disorder; Vascular disease; neuroprotection; Central nervous system disease; Hypoxia; Preconditioning; Cerebrovascular disease
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.STR.0000206444.29930.18

Hypoxia preconditioning (HPC), rapid or delayed, has been reported to induce neuroprotection against subsequent severe stress. Because delta-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. 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 micromol/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. 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. DOR is involved in neuroprotection induced by rapid HPC in cortical neurons.