Ischemic injury glutamate-mediated

Amacrine cells, an important class of interneurons of the inner retina, are also sensitive to ischemia and glutamate excitotoxicity. Ischemia upregulates expression of proinflammatory mediators such as COX-2 and iiNOS in amacrine cells (Ju et al., 2003). These molecules also are involved in ischemic injury to the ganglion cells, suggesting that common mechanisms of ischemic injury exist in different cells. Both of these cell types die by apoptosis (Singh et al., 2001). Amacrine cells are morphologically, functionally, and molecularly diverse, thus not all amacrine cells are equally susceptible to ischemia or excitotoxicity (Osborne and Larsen, 1996). 

Ionotropic glutamate receptors also promote perturbations in ionic homeostasis that play a critical role in cerebral ischemia. For example, L, P/Q, and N-type calcium channel receptors mediate excessive calcium influx, and Ca " channel antagonists reduce ischemic brain injury in preclinical studies [12-14]. Zinc is stored in vesicles of excitatory neurons and coreleased upon depolarization after focal cerebral ischemia, resulting in neuronal death [15, 16]. Recently, imbalances in potassium have also been implicated in ischemic cell death. Compounds that selectively modulate a class of calcium-sensitive high conduc-tance potassium (maxi-K) channels protect brain against stroke in animal models [17]. 

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