Effects of NMDA Antagonists and Temperature on Regional Cerebral Blood Flow

Abstract

A large body of experimental data supports the excitotoxic hypothesis of ischemic brain damage [1,2], where the ischemic insult results in a massive pathological release of excitatory amino acids that eventually leads to a lethal influx of calcium into the neurons. within the framework of excitotoxic ischemic injury, blockade of NMDA receptors and calcium channels may prevent neuronal damage and death [1]. This therapeutic strategy, therefore, relies primarily on the prevention of pathologic activation of NMDA-gated calcium channels, and does not involve improvements of regional cerebral blood flow (rCBF) per se. Mild to moderate hypothermia also appears to protect against cerebral ischemic injury [3,4]. Changes in temperature of a few degrees can significantly decrease the release of excitotoxic amino acids during the ischemic episode [4]. However, it is possible that NMDA antagonists and hypothermia may also influence blood flow, either directly, through secondary alterations related to cerebral metabolism, or by modifications of normal autoregulatory mechanisms including changes in metabolism-flow coupling. There changes may also vary with the specific type of NMDA antagonist, dose, animal species, the use of anesthesia, and the degree of hypothermia involved.