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Chapter 8 Antagonism of the NMDA and non-NMDA receptors in global versus focal brain ischemia

1993; Elsevier BV; Linguagem: Inglês

10.1016/s0079-6123(08)63262-8

1875-7855

William A. Pulsinelli, Abigail Sarokin, Alastair M. Buchan,

Pain Mechanisms and Treatments

This chapter discusses the role of the N-methyl-D-aspartate NMDA receptor/channel in ischemic stroke studies, and proposes an explanation for the disparate results associated with its use in animal models of global brain ischemia. The chapter presents recent data on alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor blockade and highlights why these new antagonists may become the most important therapeutic agents to date in attenuating neuronal damage caused by stroke. Much of the research has focused on the NMDA receptor/channel's function in injury from global and focal brain ischemia because this channel is known to be permeable to calcium ions. However, while there is largely a consensus among investigators that antagonists of the NMDA receptor/channel reduce infarction volume in animal models of focal brain ischemia, there is a lack of agreement as to their effectiveness in models of transient but severe forebrain ischemia. Regarding clinical applicability, it is concluded that although both the NMDA and AMPA receptor antagonists may prove effective in combatting the effects of focal brain ischemia (stroke), the AMPA receptor antagonist alone appears to offer hope for treating the effects of global brain ischemia.