Long-Term Consequences of Hypoxia During the Perinatal Period of Development on the Structural-Functional Characteristics of the Brain in Rats

Abstract

The experiments reported here showed that acute hypoxia during the perinatal period of development leads to structural changes in the motor and visual areas of the neocortex, detectable by postnatal day 20 as impairments to the structural organization of the layers of the neocortex. We report the first data showing that different hippocampal fields respond differently to hypoxia during the postnatal period and present evidence for the existence of long-term sequelae of perinatal hypoxia in the structure of the hippocampus. Acute hypoxia was followed by cell death in all fields and thinning of the pyramidal neuron layers. The greatest levels of cell death occurred in fields CA4 and CA3. As postnatal age increased, cell death remained significant in field CA4, decreased in field CA3, and was not seen in field CA1, though granule neuron death in the dentate fascia increased with increasing age. In addition, there were decreases in the sizes of pyramidal neuron cell bodies in all hippocampal fields. All hippocampal fields showed activation of astrocyte reactions, more marked in field CA4, where gliosis persisted to prepubertal age. Hypoxia in the early postnatal period could have effects on synaptogenesis, particularly on the formation of giant synapses in the dentate fascia. Studies of the functional characteristics of the nervous system in such animals showed that hypoxia could induce significant impairments in behavioral reactions. Rats of the experimental group showed impairments to the inhibitory functions of the cerebral cortex, increased anxiety, and disturbances to spatial learning and working memory.