Histological changes and neurotransmitter levels three months following perinatal asphyxia in the rat

The involvement of excitatory amino acids (EAA) in the pathogenesis of hypo xic-ischemic states is well-documented. Information on the role of overexci tation by EAA in perinatalasphyxia (PA), however, is limited and data from adult models cannot be directly extrapolated to immature systems. Moreover, most adult models of ischemia are representing stroke rather than PA. We d ecided to study long term effects in a non-invasive rat model of PA resembl ing the clinical situation three months following the asphyctic insult. Mor phometry on Nissl - stained sections was used to determine neuronal death i n frontal cortex, striatum, hippocampus CA1, hypothalamus and cerebellum L1 , and the amino acids glutamate, glutamine, aspartate, GABA, taurine, argin ine as well as histamine, serotonin and 5-hydroxy-indoleacetic acid were de termined in several brain regions and areas. Morphometry revealed that neur onal loss was present in the hippocampal area CA1 in all groups with PA and that morphological alterations were significantly higher in the cerebellar granular layer. The prominent light microscopical finding in all areas of asphyctic rats studied was decreased Nissl-staining, suggesting decreased c ellular RNA levels. Glutamate, aspartate and glutamine were significantly e levated in the hypothalamus of asphyctic rats probably indicating overstimu lation by EAA. Excitotoxicity in this area would be compatible with finding s of emotional / behavioral deficits observed in a parallel study in our mo del of PA. Our observations point to and may help to explain behavioral and emotional deficits in Man with a history of perinatal asphyxia.