DEVELOPMENTAL-CHANGES IN [H-3] KAINATE BINDING IN HUMAN BRAIN-STEM SITES VULNERABLE TO PERINATAL HYPOXIA-ISCHEMIA

The human brainstem is especially susceptible to hypoxia-ischemia in e arly life. To test the hypothesis that the period of vulnerability of the developing human brainstem to hypoxia-ischemia correlates with a t ransient elevation in kainate receptor binding, we compared the quanti tative distribution of [H-3]kainate binding in brainstem nuclei betwee n four fetuses (19-26 gestational weeks), four infants (one to nine mo nths), and three ''mature'' individuals (one child and two adults) wit hout neurological disease. Quantitative tissues autoradiography was us ed. [H-3]Kainate binding decreased in all brainstem regions from early life to maturity with the most significant decreases occurring in nuc lei thought to be especially vulnerable to perinatal hypoxia-ischemia (e.g. principal inferior olive, griseum pontis, inferior colliculus an d reticular core). The highest binding in the fetal and infant period was found primarily in the major cerebellar-relay nuclei. In the infer ior olive and arcuate nucleus, binding increased from the fetal to the infant period, and then fell 50-61% to low mature levels. In the gris eum pontis, binding decreased 60% between the fetal and mature periods . In the reticular formation, binding fell 67-78% from the fetal to ma ture period. These data support a correlation between the period of br ainstem vulnerability to hypoxia-ischemia in early life to a transient elevation in kainate binding, and are particularly relevant to the to pographic brainstem patterns in perinatal hypoxia-ischemia of infantil e olivary gliosis, pontosubicular necrosis and reticular core damage. Striking localization of [H-3]kainate binding to rhombic lip derivativ es further suggests that kainate receptors may be involved in the deve lopment and function of human brainstem-cerebellar circuitry.