The Role of Zinc in Cerebral Ischemia

Abstract

Ischemic stroke is one of the most pervasive life-threatening neurological conditions for which there currently exists limited therapeutic intervention beyond prevention. As calcium-focused neuroprotective strategies have met with limited clinical success, it is imperative that alternative therapeutic targets be considered in the attempt to antagonize ischemic-mediated injury. As such, zinc, which is able to function both as a signaling mediator and neurotoxin, has been implicated in cerebral ischemia. While zinc was first purported to have a role in cerebral ischemia nearly twenty years ago, our understanding of how zinc mediates ischemic injury is still in its relative infancy. Within this review, we examine some of the studies by which zinc has exerted either neuroprotective or neurotoxic effects during global and focal cerebral ischemia.

Cardioprotective effect of zinc requires ErbB2 and Akt during hypoxia/reoxygenation

“…Many in vitro and in vivo studies have examined the role of zinc during both global and focal cerebral ischemia. These studies, direct (using zinc chloride or zinc protoporphyrin) and indirect (using chelators of zinc) have reported zinc to possess either neurotoxic or neuroprotective capabilities in a temporal manner in experimentally induced ischemia (see review, Galasso and Dyck 2007). This inconsistency may have arisen due to employment of different model systems and much more needs to be learnt about the critical role of zinc in brain ischemia.…”

“…It was argued that calcium may act as an accomplice to zinc and their cellular transients can be influenced by each other in potentially mediating ischemic injury in the brain. Translocation of zinc from presynaptic neurons to specific postsynaptic neurons was shown to be responsible for cerebral ischemic injury (Galasso and Dyck 2007).…”

The role of zinc in immunity and inflammation

“…In this context, elevated levels of intracellular free zinc seem to play a major part in neuronal death after seizures or ischaemia (Choi et al, 1998;Galasso et al, 2007). Zinc deficiency does also have pro-apoptotic effects.…”

Autophagy Mediates Astrocyte Death During Zinc-Potentiated Ischemia–Reperfusion Injury

“…Many efforts have been directed toward understanding the molecular events involved in brain injury from cerebral ischemia. Following ischemic stroke, zinc is released from a subset of glutamatergic terminals in the brain [1]. A previous study shows that extracellular zinc could be brought to more 100 μM by synaptically released zinc [2].…”