ABSTRACT
When the brain is deprived of oxygen and glucose, a cascade of events begins that can rapidly result in substantial cell death. One early step in this cascade is the release of excitatory neurotransmitters such as glutamate,14 which activate N-methyl D-aspartate (NMDA)-receptors and so induce a massive calcium entry into neurons. 4,9 This process is known as excitotoxicity, because cells literally excite themselves to death. Consequently, the uncontrolled influx of calcium indiscriminately activates gene expression and intracellular enzymes such as proteases. lg,20 Excitotoxicity also induces the production of lethal oxygen-free radicals such as superoxide and hydroperoxide. In These highly reactive oxidant species indiscriminately damage cell membranes and proteins and, if neurons survive that, oxidants also induce a program of delayed cell death (apoptosis). The exact processes by which toxic radicals are formed during ischemia are still being elucidated, but oxidants appear to be formed by stressed mitochondria, as they attempt to continue ATP production under conditions of limited oxygen and glucose availability.l,6.7
CANNABINOIDS AND ISCHEMIA
The idea of using cannabinoids to treat ischemia may initial1y seem surprising, and administration of psychoactive cannabinoids could certainly present problems as a treatment for cerebral ischemia, For example, an elderly and confused stroke patient would probably prefer not to take a drug that can further increase anxiety and confusion. Similarly, physicians would need to complete any neurological exmnination before administering psychoactive cannabinoids, since they affect motor coordination and other neurological responses, However, it should be remembered that cerebral ischemia is the third most common cause of death in adults in the developed world and current available treatment options are extremely limited and not without risk.25
