부산대학교 도서관

Ischemic stroke is one of the leading causes of death and disability worldwide. The inhibition of cerebral blood flow triggers intertwined pathological events, resulting in cell death and loss of brain function. Interestingly, animals pre-exposed to short-term ischemia can tolerate subsequent severe ischemia. This phenomenon is called ischemic tolerance and is also triggered by other noxious stimuli. However, whether short-term exposure to non-noxious stimuli can induce ischemic tolerance remains unknown. Recently, we found that pre-exposing mice to an enriched environment for 40 min is sufficient to facilitate cell survival after a subsequent stroke. The neuroprotective process depends on the neuronal activity soon before stroke, of which the activity-dependent transcription factor Npas4 is essential. Excessive Ca2+ influx triggers Npas4 expression in ischemic neurons, leading to the activation of neuroprotective programs. Pre-induction of Npas4 in the normal brain effectively supports cell survival after stroke. Furthermore, our study revealed that Npas4 regulates L -type voltage-gated Ca2+ channels through expression of the small Ras-like GTPase Gem in ischemic neurons. Ischemic tolerance is a good model for understanding how to promote neuroprotective mechanisms in the normal and injured brain. Here, we highlight activity-dependent ischemic tolerance and discuss its role in promoting neuroprotection against stroke. • Neuronal activity promotes ischemic resistance in neurons (activity-dependent ischemic tolerance). • The transcription factor Npas4 induces activity-dependent ischemic tolerance. • Npas4 suppresses L -type voltage-gated Ca2+ channels via the small GTPase Gem. • Npas4 pre-induction in the normal brain promotes cell survival after stroke. • Activity-dependent ischemic tolerance is a good model for studying neuroprotection. [ABSTRACT FROM AUTHOR]