HYPOXIA AND BRAIN-DEVELOPMENT

Hypoxia threatens brain function during he entire life-span starting f rom early fetal age up to senescence. This review compares the short-t erm, long-term and life-spanning effects of fetal chronic hypoxia and neonatal anoxia on several behavioural paradigms including novelty-ind uced spontaneous and learning behaviours. Furthermore, it reveals that perinatal hypoxia is an additional threat to neurodegeneration and de cline of cognitive and other behaviours during the aging process, Pren atal hypoxia evokes a temporary delay of ingrowth of cholinergic and s erotonergic fibres into the hippocampus and neocortex, and causes an e nhanced neurodegeneration of 5-HT-ir axons during aging. Neonatal anox ia suppresses hippocampal ChAT activity and up-regulates muscarinic re ceptor sites for H-3-QNB and H-3-pirenzepine binding in the hippocampu s in the early postnatal age. The altered development of axonal arbori zation and pre- and postsynaptic cholinergic functions may be an impor tant underlying mechanism to explain the behavioural deficits. As far as the cellular mechanisms of perinatal hypoxia is concerned, our prim ary aim was to study the putative importance of Ca2+ homeostasis of de veloping neurons by means of pharmacological interventions and by meas uring the development of immunoexpression of Ca2+-binding proteins. We assessed that nimodipine, an L-type calcium channel blocker, prevente d or attenuated the adverse behavioural and neurochemical effects of p erinatal hypoxias, while it enhanced the early postnatal development o f ir-Ca2+-binding proteins. The results are discussed in the context o f different related research areas on brain development and hypoxia an d ischaemia. Copyright (C) 1996 Elsevier Science Ltd