Neuroprotective effect of thyrotropin-releasing hormone against excitatory amino acid-induced cell death in hippocampal slices.
Thyrotropin-releasing hormone (TRH) and some of its stable analogues have recently been shown to improve functional recovery after neurologic dysfunctions, such as brain trauma and epilepsy, in both animals and humans. The exact mechanism by which TRH produces its neuroprotective effects is still uncertain. The present study provides the first evidence that TRH exerts a neuroprotective effect against N-methyl-D-aspartate (NMDA)-mediated excitotoxicity in rat hippocampal slices. TRH concentration dependently reduced NMDA toxicity by a mechanism that was highly sensitive to the protein kinase C blocker, bisindolilmaleimide. Delayed application of TRH, during NMDA exposure, still produced neuroprotection.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*