Secondary mechanisms in neuronal trauma

D. R. Lynch, Ted M Dawson

Research output: Contribution to journalArticle

Abstract

Secondary damage in central nervous system trauma results from toxic effects of a variety of modulators that magnify the initial traumatic damage. These modulators include the excitatory transmitter glutamate, the intracellular messenger calcium, and the intercellular messenger nitric oxide. Glutamate-induced toxicity, called excitotoxicity, occurs from excess glutamate release following trauma. Passage of calcium into the cell through a specific postsynaptic glutamate receptor ion channel, the N-methyl-D-aspartate (NMDA) receptor, is crucial in activating cellular pathways leading to excitotoxic damage. The NMDA receptor requires both glutamate and glycine for activation and is blocked by many drugs that act at either of these sites. It is also blocked by agents that selectively block the ion channel of this receptor. Blocking NMDA receptors at any of these sites decreases the cellular damage mediated by glutamate in neuronal trauma and improves physiological measures associated with traumatic damage. Other strategies to limit secondary damage include blockade of other calcium channels, of calcium-activated enzymes, and of processes that mediate the effects of calcium. Calcium-activated enzymes include nitric oxide synthase and phospholipases, which cause production of free radicals. In combination with NMDA receptor blockade, these sites represent promising areas for therapeutic intervention in secondary traumatic damage.

Original languageEnglish (US)
Pages (from-to)510-516
Number of pages7
JournalCurrent Opinion in Neurology
Volume7
Issue number6
StatePublished - 1994

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Glutamic Acid
N-Methyl-D-Aspartate Receptors
Calcium
Wounds and Injuries
Ion Channels
Nervous System Trauma
Phospholipases
Poisons
Glutamate Receptors
Enzymes
Calcium Channels
Nitric Oxide Synthase
Glycine
Free Radicals
Nitric Oxide
Central Nervous System
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Secondary mechanisms in neuronal trauma. / Lynch, D. R.; Dawson, Ted M.

In: Current Opinion in Neurology, Vol. 7, No. 6, 1994, p. 510-516.

Research output: Contribution to journalArticle

Lynch, D. R. ; Dawson, Ted M. / Secondary mechanisms in neuronal trauma. In: Current Opinion in Neurology. 1994 ; Vol. 7, No. 6. pp. 510-516.
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