Excitotoxic injury refers to trans-synaptic injury due to release of excitatory amines, which occurs in the peripheral and central nervous system. The way the brain responds to traumatic stimulation, prolonged seizures, and hypoxia causing the release of excitatory amines, the so called excitotoxic mechanism, seems to be different in infants, children and adults. Excitotoxic mechanisms are also related to some neurodegenerative diseases in pediatric patients. This exhibit illustrates various diseases associated with excitotoxic mechanisms in the pediatric brain on CT and MRI, including diffusion-weighted imaging (DWI) and proton MR spectroscopy (MRS).

Excitotoxic Mechanisms in Pediatric Brain

Glutamate, aspartate and glycine are the dominant excitatory amino acids and the primary neurotransmitters in about half of all the synapses in the brain. Glutamate is the most important and is responsible for many neurologic functions including cognition, memory, movement and sensation. In pathological conditions, glutamate mediates neuronal injury or death, particularly through activation of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor⁽¹⁾.

The post-natal period of brain development is particularly vulnerable to excitotoxic injury. Excitatory amino acid receptors are abandant in the cortex during the 1st two year of life. The high rate of generation of synapses (synaptogenesis) results in an overexpression of the receptor. NMDA receptors dominate in the immature brain when synaptic transmission is weak and extremely plastic. Experimental studies show that too much or too little NMDA receptors can be threatening to developing neurons⁽²⁾. During maturation, non-NMDA receptors, Alpha-amino-3-hydroxy-5-methyl-5-isoxazolepropionate (AMPA) receptor and kainic receptor, predominate.

Neuronal glutamate is released from the pre-synaptic terminal into the synaptic cleft. The glutamate binding to non-NMDA receptors allows entry of Na+ into the post-synaptic neuron, resulting in cytotoxic edema. The glutamate binding to NMDA receptors allows entry of Ca2+ into the post-synaptic neuron resulting in necrotic cell death or apoptosis. Re-uptake of extracellular glutamate is done at the pre-synaptic terminals and adjacent glial cells. (Figure 1).