Abstracts

We used the rat in utero radiation model of cortical dysplasia (CD), which is characterized postnatally (P) by neuronal dyslaminations, polarity disorientations, and daily increases in cortical thickness. At P30 these rats may exhibit cortical seizures from the region of the permanent CD. Because the CD is present at birth and increases daily in size with the growth of neurons and dendrites, we hypothesized that a permanent increase in NMDA receptor densities may develop early in the first week to enhance CD neurons[apos] excitability., Dams were radiated with 145 Rads (cGy) at embryonic day 17 (E17), their offspring were studied at 24 hour intervals, postnatal ages P0-10 and P21-36. The development of CDs measured neuron sizes and neuron densities in cortical layers II-V. Densities were compared to age matched controls using stereology. In siblings, expressions of NMDA receptor subunits NR1 and NR2B were measured by immunocytochemistry and Western blotting. Statistics between control and radiated age matched pups were made between treatments and across ages., Daily increases in neuron sizes were found from P0 through P10 in both groups, and after that there were no greater cytoplasmic increases in either group. At P0 and P1 nearly all neurons were spherical or oval in shape, lacking dendritic processes. At P2 neurons developed larger cytoplasms and larger proximal dendrites, which gave the neurons a pyramidal shape in all cortical layers. Growth of dendritic and axonal processes began at P2 and continued after P10. The expression levels for NR1 and NR2B at P0 and P1 were low, but increased significantly by P2; however, this increase plateaued after P2 and through P10. It is important to note that these developmental patterns were the same for both radiated and nonradiated pups., We used the rat in utero radiation model to identify postnatal malformations of cortical neurons and their NMDA receptor subunit expressions. During the earliest postnatal period, P0-P10 the cortex is expanding with increasing neuron sizes and neuritic outgrowths. Only P0 and P1 had significantly immature neurogenesis, with small, round neurons lacking dendrites and having the lowest NMDA receptor expressions. At P2-P10 neuron sizes and dendritic lengths increased. Also, at P2 NMDA expressions were maximal, and neither NR1 nor NR2B expressions increased on subsequent days. These developmental patterns in neurons and receptors were the same for control and radiated rats that always had permanent CD starting at birth. Hence, the later (P30) process of epilepsy likely occurs when all the axo-dendritic synapses, including aberrant excitatory connections within the CD, are fully mature., (Supported by: 1) NIH Grant NS41375; 2) The Frankel Family Endowed Chair in Pediatric Neuroscience.)