Transient Receptor Potential Melastatin 2 ( TRPM 2 ) Channel Plays a Role in Neonatal Hypoxic-Ischemic Brain Injury

Recent advances in stroke research have identified non-glutamate mechanisms associated with ischemic neuronal death in adults. Among the molecules involved in non-glutamate mechanisms, transient receptor potential melastatin 2 (TRPM2), a calcium-permeable non-selective cation channel, is reported to mediate brain damage following ischemic insults in adult mice. However, the role of TRPM2 channels in neonatal hypoxic-ischemic brain injury remains unknown. Here, we propose that TRPM2-null mice (TRPM2 +/and TRPM2 -/) reduces neonatal hypoxic-ischemic brain injury in postnatal 7-day-old mice. We report that the infarct volumes are significantly smaller and behavioral outcomes are improved in neonatal TRPM2 +/and TRPM2 -/mice compared to wild type mice. Next, we found that TRPM2-null mice down-regulated GSK-3β activity following HI. We subsequently tested the role of GSK-3β in neonatal HI brain injury using the pharmacological blocker TDZD-8. We showed that GSK-3β activity is involved in apoptotic neuronal cell death that could link the Akt/GSK-3β/caspase-3 pathway.