Ibuprofen protects ischemia-induced neuronal injury via up-regulating interleukin-1 receptor antagonist expression.
The inflammatory response accompanies and exacerbates the developing injury after cerebral ischemia. Ibuprofen, a non-steroidal anti-inflammatory drug, has been shown to attenuate injuries in animal models of various neurological diseases. In the present study, we investigated ibuprofen's neuroprotective effects in rats exposed to transient forebrain ischemia and in cultures exposed to oxygen glucose deprivation (OGD). Rats treated with ibuprofen after transient forebrain ischemia displayed long-lasting protection of CA1 hippocampal neurons. There were selective increases in interleukin-1 receptor antagonist gene and protein expression in ibuprofen-treated OGD microglia. Furthermore, treatment with ibuprofen in neuron/microglia co-cultures increased the number of surviving HC2S2 neurons against OGD whereas IL-1ra neutralizing antibody reversed the ibuprofen-induced neuroprotection. The data indicate that ibuprofen-induced IL-1ra secretion is involved in neuroprotection against ischemic conditions.
Park
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EM
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, W. M. Burke Medical Research Institute, White Plains, NY 10605, USA.
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D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015153:Blotting, Western / Q000379:methods; D002545:Brain Ischemia / Q000150:complications / Q000517:prevention & control*; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D018920:Coculture Techniques / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D000860:Hypoxia; D007052:Ibuprofen / Q000627:therapeutic use*; D007150:Immunohistochemistry / Q000379:methods; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D005947:Glucose; D007052:Ibuprofen