The rationale for glutamate antagonists in the treatment of traumatic brain injury.
The recent development of potent antagonists for the most widespread neurotransmitter in the mammalian brain has opened up possibilities for many forms of therapy. The excitotoxic hypothesis implicates excessive release of excitatory amino acids (EAAs) as an important cause of brain damage, especially in acute ischemia, and chronic neurodegeneration. Focal ischemic damage and diffuse axonal injury are the major causes of brain damage after traumatic human brain injury. Evidence from animal models has shown that excitatory amino acid-induced events maybe responsible for a proportion of the posttraumatic sequelae and that these effects can be blocked by EAA antagonists. This evidence is reviewed, and the implications for human pathophysiology and treatment are discussed.
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology / Q000517:prevention & control*; D006259:Craniocerebral Trauma / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D018846:Excitatory Amino Acids / Q000502:physiology; D006408:Hematoma, Subdural / Q000503:physiopathology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000503:physiopathology; D008959:Models, Neurological; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate