Excitotoxicity in perinatal brain injury

Michael V. Johnston

Research output: Contribution to journalArticlepeer-review

220 Scopus citations


Excitotoxicity is an important mechanism involved in perinatal brain injuries. Glutamate is the major excitatory neurotransmitter, and most neurons as well as many oligodendrocytes and astrocytes possess receptors for glutamate. Perinatal insults such as hypoxia-ischemia, stroke, hypoglycemic, kernicterus, and trauma can disrupt synaptic function leading to accumulation of extracellular glutamate and excessive stimulation of these receptors. The activities of certain glutamate receptor/channel complexes are enhanced in the immature brain to promote activity-dependent plasticity. Excessive stimulation of glutamate receptor/ion channel complexes triggers calcium flooding and a cascade of intracellular events that results in apoptosis and/or necrosis. Recent research suggests that some of these intracellular pathways are sexually dimorphic. Age dependent expression of different glutamate receptor subtypes with varying abilities to flux calcium has been associated with special patterns of selective vulnerability at different gestational ages. For example, selective injury to the putamen, thalamus and cerebral cortex from near total asphyxia in term infants may be related to excessive activation of neuronal NMDA and AMPA type glutamate receptors, while brain-stem injury may be related primarily to stimulation of neuronal AMPA/kainate receptors. In contrast, periventricular leukomalacia in premature infants has been linked to expression of AMPA/kainate receptors on immature oligodendrocytes. Insight into the molecular pathways that mediate perinatal brain injuries could lead to therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)234-240
Number of pages7
JournalBrain Pathology
Issue number3
StatePublished - Jul 2005
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology


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