| In recent years, improvement in diagnostic techniques has led to better recognition of "disorders of cortical development". These disorders constitute a significant cause of epilepsy, mental retardation, developmental delay and neurological deficits in childhood, and may also contribute to the pathogenesis of psychological and neurodegenerative diseases in adults. Hitherto, however, few systematic studies of the human fetal cortex have been performed, and little is known about the ontogenetic processes of the neocortex in man.; The question addressed in this thesis is: How does the human neocortex develop? The aim of the study is to establish a preliminary understanding of the developmental events that occur in the second and third trimesters of gestation, by investigating the morphological and biochemical patterns of development of the human neocortex during this period. The histology of the immature brain is studied using Nissl and Golgi methods. The temporal and spatial patterns of expression of the cell proliferation marker proliferating cell nuclear antigen (PCNA), the neuronal markers gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT), dopamine beta hydroxylase (DBH), dopamine receptor DR1 and synaptophysin, as well as the glial cell markers glial fibrillary acidic protein (GFAP), S100B and excitatory amino acid transporter protein GLT-1 are delineated in the fetal cortex using immunohistochemistry.; Results of this study showed that cell proliferation in the germinative zones lasts till 27 weeks of gestation in human neocortex. The six cortical layers appear between 21 to 27 weeks of gestation. Cell differentiation extends from week 14 of gestation to beyond term. Different neuronal and glial cell proteins follow different developmental patterns and many show inter- or intra-regional variations in expression. Details of these patterns are described and discussed in this thesis. The early expression of these proteins suggests that they play important roles in the developmental processes of cell proliferation, migration and differentiation. Both neurotransmitters and glial cell proteins probably function outside the confines of synapses in the fetal brain, as paracrine/autocrine factors. Early developmental events seem to be dictated by an innate programme, whereas late events may be more susceptible to extrinsic influence.; It is hoped that knowledge of the normal developmental process can lead to better understanding of the causes and mechanisms of "disorders of cortical development", and to better treatment. |
