Zinc overload in stroke

Abstract

Although zinc (Zn or Zn2+) signals are necessary for cell communication and survival, abnormal cellular zinc load can be a precursor for cell death and subsequent brain degeneration following a stroke. Zinc mediates cell death by causing mitochondrial dysfunction, by reinforcing apoptotic signaling cascades, and by inhibiting neuronal metabolism. The mechanisms leading to the sustained zinc dysregulation in excitotoxic conditions are only in part elucidated. This chapter examines the cytotoxicity and sources of zinc overload, and its interaction with neurotransmitter receptors/ion channels. Recent studies show that zinc can be released through the mobilization of zinc from intracellular stores such as mitochondria and endoplasmic reticulum. Changes in the expression of zinc transporters may also be responsible for zinc dyshomeostasis. The question of possible interplays between zinc and calcium overloads in ischemic-hypoxia and oxidative stress are also discussed. Although zinc-induced damage seem to follow the similar trajectory of cell death that has been recognized for calcium overload, neurons appear to be more sensitive to zinc-mediated toxic effect. Therefore, an effective therapeutic strategy for stroke may be a combined treatment that also targets the multiple events involved in zinc dyshomeostasis.