Post-ischemic brain damage: the endocannabinoid system in the mechanisms of neuronal death (original) (raw)

A wealth of information has accumulated to date concerning the basic mechanisms underlying post-ischemic neuronal death in the mammalian brain. In the course of cerebral ischemia (i.e. stroke, trauma, cardiac arrest), abnormal levels of the excitatory amino acid glutamate build up in the brain, causing 'axon-sparing' excitotoxic neuronal death. The recognized trigger for such a devastating event is the excessive stimulation of glutamate receptors, particularly of the ionotropic [i.e. N-methyl-d-aspartate (NMDA)] subtype, which leads to the accumulation of toxic amounts of intracellular free calcium and of nitrogen and oxygen radical species, and to oxidative stress, committing the neuron to death via activation of different downstream death pathways selected in relation to the strength of the detrimental stimulus [1]. This mechanism represents