Nitric oxide in developing brain.

Abstract

The role of NO in the neonatal brain, particularly during hypoxia and ischaemia has been studied extensively in animal models of focal and global ischaemia. The n-NOS and i-NOS activation have been found to be harmful whereas e-NOS activation has a neuroprotective effect in focal ischaemia (Fig. 1). The findings following global ischaemia are somewhat more controversial. Although all these studies clearly demonstrate that NO has an important role in the neonatal brain, it may be difficult to apply the results to humans for it is not clear when and which isoform of NOS gets activated following ischaemia in newborn infants. Also it is hard to determine the timing of intervention to inhibit or stimulate the production of NO in humans since we still do not know all the details about protective mechanisms of the human body. Some interventions may have a deleterious effect on some of those mechanisms. In addition, the relatively selective NOS inhibitors which are now used in animal experiments are not appropriate for human studies. New studies regarding the production of NO following ischaemia will be needed in newborns, together with the development of selective NOS inhibitors which can be used in humans. If the NO production follows the same pattern in humans as in animals at least the effects of i-NOS may be prevented either by selective inhibitors or by neuroprotective agents.