Cerebral cortical dysplasia: Giant neurons show potential for increased excitation and axonal plasticity

Cerebral cortical dysplasia (CD) is a common cause of intractable childhood epilepsy. Five cases of CD were analyzed for GABA(A) receptor subunit beta (GABA(A beta)) glutamate decarboxylase, AMPA receptor subunit 1 (GluR1) an d subunit 2/3 (GluR2/3), and NMDA receptor 2 (NMDAR2) immunoreactivity. Ant isera to the highly po lysialylated neural cell adhesion molecule (PSA-NCAM ) and human unc-33-like phosphoprotein 1 (hUlip 1)were used to identify neu rons with 'developmentally immature' characteristics. Differences between C D and comparison tissue (n = 3) included: (1) prominent GABA(A beta) immuno reactivity of the cytoplasm of dysmorphic neurons in the subcortical white matter and cortex in 1 CD case; (2) increased immunolabeling with anti-GluR 1 and GluR2/3 antisera in dysmorphic neurons compared with more normal-appe aring adjacent neurons and neurons from nondysplastic cortex; (3) varying n umbers of cortical dysmorphic neurons stained for NMDAR2 in all 5 CD cases, in contrast to a complete lack of cellular immunoreactivity in 2/3 of the cases of nondysplastic cortex; (4) PSA-NCAM and hUlip 1 expression (usually observed only in populations of neurons that undergo axonal growth) was ob served in CD tissue, but not in normal brain tissue. In summary, dysmorphic neurons in cases of CD have increased immunoreactivity for several excitat ory neurotransmitter receptor subunits, show variable immunoreactivity for GABA(A beta) and show expression of several proteins that are normally expr essed only in immature neurons or those with the potential for synaptic pla sticity. Copyright (C) 1999 S.Karger AG, Basel.