Alcohol-induced neuropathology in the neonatal rat brain.

摘要

The most debilitating consequence of fetal alcohol exposure (FAS) is damage to the developing nervous system. The experiments in this thesis examine the toxic effects of alcohol exposure during the brain growth spurt of the rat.; Experiments in the first part of the thesis examine two facets of FAS neuropathology. (1) Alcohol-induced astrogliosis and (2) Alcohol-induced death of cortical neurons. Astrogliosis was examined in layer V of the cerebral cortex following several different alcohol exposure paradigms. Alcohol-exposure from PD 4-10 resulted in a two-fold increase in the number of glial fibrillary acidic protein (GFAP) positive astrocytes in layer V and also prominent sites of gliosis around cortical blood vessels. Shorter alcohol exposure times from PD 4-6 and PD 4-7 also resulted in gliosis, while the gliosis following PD 4-5 was not as evident. Alcohol exposure from PD 10-14 also resulted in layer V gliosis, however there was no obvious sign of gliosis surrounding the blood vessels. Alcohol-induced neuronal cell loss was also examined following exposure from PD 4-9. This exposure pattern resulted in a 15% loss of cerebral cortical neurons. The neurons are postmitotic at this point, thus the neuronal loss is due to direct killing and not inhibition of proliferation.; The second part of this thesis examined a potential mechanism of alcohol-induced loss of cerebellar granule cells. The experiments stem from earlier studies showing that N-methyl- scD-aspartate (NMDA) will protect granule cells in culture from the harmful effects of alcohol. Results show that inhibition of nitric oxide synthase (NOS) blocks NMDA mediated neuroprotection. In addition, the time course of NOS was examined in the cerebellum using the NADPH-diaphorase histochemical stain and NOS immunostaining. On PD 1, the granule cells are lightly reactive and the staining increases up until PD 11 where they are intensely stained. The granule cells remain stained in the adult animal. Purkinje cells, which in the mature animal do not stain, are NADPH-diaphorase and NOS immuno-positive from PD 1 thru PD 18, although there is a gradient in the staining.