[Brain zinc dyshomeostasis and glial cells in ischemic stroke].

Zinc, an essential trace element, plays an important role in a large number of biological functions. In mammalian brain, whereas the majority of brain zinc is bound to proteins including metallothionein, about 5-15% is stored in presynaptic vesicles of glutamatergic neurons throughout the forebrain, especially in the hippocampus, in a relatively free state. Thus, free zinc (Zn) concentration in the brain is considered to be regulated in order to maintain normal brain functions such as learning and memory. On the other hand, brain Zn dyshomeostasis has been recognized as a mechanism for neuronal injury in brain disorders including Alzheimer's disease and brain ischemia. In particular, after transient brain ischemia, Zn accumulates in hippocampal neurons via a zinc transport system, or via release from cytosolic zinc-binding proteins, which results in neuronal cell death. Recently, it has been demonstrated that Zn dyshomeostasis also occurs in glial cells such as microglia, astrocytes and oligodendrocytes after brain ischemia. In oligodendrocytes, ischemic insult triggers intracellular Zn accumulation, resulting in cell death via mitochondrial dysfunction. Increased extracellular Zn inhibits astrocytic glutamate uptake. In addition, extracellular Zn massively released from ischemic neurons primes microglia to enhance production of pro-inflammatory cytokines in response to stimuli that trigger M1 activation. This review aims to describe the impact of brain Zn dyshomeostasis on alterations in glial cell survival and functions in post-ischemic brains.