Elsevier

Brain and Development

Volume 17, Issue 5, September–October 1995, Pages 301-306
Brain and Development

Neurotransmitters and vulnerability of the developing brain

https://doi.org/10.1016/0387-7604(95)00079-QGet rights and content
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Abstract

The immature human brain undergoes remarkable organizational changes during intrauterine and postnatal life. These changes create potential temporal ‘windows’ of selective vulnerability to damage. For example, the temporary germinal matrix is vulnerable to hemorrhage in the third trimester fetus and premature infant. The immature oligodendroglia present in developing white matter of the fetus are also vulnerable to injury producing periventricular leukomalacia. Similar changes take place in the synapses that make up the infant's neuronal circuitry. In human cerebral cortex, synapses are produced in greater than adult numbers by postnatal age 2 years and then reduced over the next decade. Over the same period receptors for glutamate, the most important excitatory neurotransmitter, change their characteristics to allow them to participate in activity dependent synaptic plasticity. For example, the immatureN-methyl-d-aspartate (NMDA) type glutamate receptor/channel complex, which plays important roles in long term potentiation (LTP), neuronal migration and synaptic pruning, contains subunits that allow the channel to be opened more easily for a longer period than adult channels. These developmental changes make the immature brain selectively vulnerable to NMDA receptor overstimulation that can occur during hypoxia-ischemia and other insults. Several types of neuropathology in the developing brain can be understood on the basis of these organizational principles.

Keywords

Glutamate
NMDA
Neurotransmitter
Synapse
Development

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Presented by invitation in the ‘Decade of the Brain’ Plenary Session at the First Conjoint Congress of the Child Neurology Society and the International Child Neurology Association in San Francisco, 2–8 October 1994.