Current Concepts of Excitotoxicity

• Published in: Journal of neuropathology and experimental neurology 1996-01, Vol.55 (1), p.1-13
• Main Author: Whetsell, William O
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Central Nervous System - drug effects; Glutamic Acid - pharmacology; Medical sciences; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neurotoxins - metabolism; Receptors, Glutamate - drug effects; Receptors, Glutamate - metabolism
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/00005072-199601000-00001

Both the original concept of excitotoxicity and the term itself were introduced by Olney in the early 1970s, based on observations by Olney and his colleagues as well as earlier observations described by Lucas and Newhouse and others. Those observations collectively construed that excessive amounts of the intrinsic excitatory amino acid (EAA) glutamate (GLU) were capable of exciting central nervous system (CNS) neurons to such an extent as to become toxic, ultimately killing GLU-sensitive neurons through over-excitation. Subsequently it was observed that another intrinsic EAA, the GLU analog aspartate (ASP), was also capable of inducing an excitotoxic effect, and the search was on to elucidate the mechanism(s) of excitotoxicity. Over the last 25 years, what originally appeared to be the relatively straightforward observation that on specific neurons GLU-receptors, when excited sufficiently, produce post-synaptic swelling first seen along dendrites (dendrosomatic swelling) and eventually progress to produce swelling and rupture of neurons, has been elaborately investigated and expanded. Research has demonstrated that what was once thought to be a singular receptor for GLU on GLU-sensitive neurons is actually a family of GLU-sensitive receptors made up of subtypes which are selectively sensitive to a number of different GLU-analogs, including substances intrinsic to the mammalian nervous system, substances occurring in nature but not found naturally in the nervous system, and several synthetic compounds which have either chemical structural analogy or functional analogy to GLU and ASP.