title: Brain development and susceptibility to damage; ion levels and movements.
abstract: Responses of immature brains to physiological and pathological stimuli often differ from those in the adult. Because CNS function critically depends on ion movements, this chapter evaluates ion levels and gradients during ontogeny and their alterations in response to adverse conditions. Total brain Na(+) and Cl(-) content decreases during development, but K(+) content rises, reflecting shrinkage of the extracellular and increase in the intracellular water spaces and a reduction in total brain water volume. Unexpectedly, [K(+)](i) seems to fall during the first postnatal week, which should reduce [K(+)](i)/ [K(+)](e) and result in a lower V(m), consistent with experimental observations. Neuronal [Cl(-)](i) is high during early postnatal development, hence the opening of Cl(-) conduction pathways may lead to plasma membrane depolarization. Equivalent loss of K(+)(i) into a relatively large extracellular space leads to a smaller increase in [K(+)](e) in immature animals, while the larger reservoir of Ca(2+)(e) may result in a greater [Ca(2+)](i) rise. In vivo and in vitro studies show that compared with adult, developing brains are more resistant to hypoxic/ischemic ion leakage: increases in [K(+)](e) and decreases in [Ca(2+)](e) are slower and smaller, consistent with the known low level of energy utilization and better maintenance of [ATP]. Severe hypoxia/ischemia may, however, lead to large Ca(2+)(i) overload. Rises in [K(+)](e) during epileptogenesis in vivo are smaller and take longer to manifest themselves in immature brains, although the rate of K(+) clearance is slower. By contrast, in vitro studies suggest the existence of a period of enhanced vulnerability sometime during the developmental period. This chapter concludes that there is a great need for more information on ion changes during ontogeny and poses the question whether the rat is the most appropriate model for investigation of mechanisms of pathological changes in human neonates.
authors.affiliation: Department of Anatomy, School of Veterinary Science, Bristol, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Erecinska
authors.forename: Shobha
authors.initials: S
authors.lastname: Cherian
authors.forename: Ian
authors.initials: I
authors.lastname: A Silver
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D006801:Humans; D000860:Hypoxia; D007477:Ions; D001523:Mental Disorders / Q000503:physiopathology*
chemical_list: D007477:Ions