Developmental changes in [3H]kainate binding in human brainstem sites vulnerable to perinatal hypoxia-ischemia.
The human brainstem is especially susceptible to hypoxia-ischemia in early life. To test the hypothesis that the period of vulnerability of the developing human brainstem to hypoxia-ischemia correlates with a transient elevation in kainate receptor binding, we compared the quantitative distribution of [3H]kainate binding in brainstem nuclei between four fetuses (19-26 gestational weeks), four infants (one to nine months), and three "mature" individuals (one child and two adults) without neurological disease. Quantitative tissues autoradiography was used. [3H]Kainate binding decreased in all brainstem regions from early life to maturity with the most significant decreases occurring in nuclei thought to be especially vulnerable to perinatal hypoxia-ischemia (e.g. principal inferior olive, griseum pontis, inferior colliculus and reticular core). The highest binding in the fetal and infant period was found primarily in the major cerebellar-relay nuclei. In the inferior olive and arcuate nucleus, binding increased from the fetal to the infant period, and then fell 50-61% to low mature levels. In the griseum pontis, binding decreased 60% between the fetal and mature periods. In the reticular formation, binding fell 67-78% from the fetal to mature period. These data support a correlation between the period of brainstem vulnerability to hypoxia-ischemia in early life to transient elevation in kainate binding, and are particularly relevant to the topographic brainstem patterns in perinatal hypoxia-ischemia of infantile olivary gliosis, pontosubicular necrosis and reticular core damage. Striking localization of [3H]kainate binding to rhombic lip derivatives further suggests that kainate receptors may be involved in the development and function of human brainstem-cerebellar circuitry.
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Department of Neurology, Children's Hospital, Boston, Massachusetts, USA.
White
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Rava
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Kinney
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D000368:Aged; D001345:Autoradiography; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D001933:Brain Stem / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002675:Child, Preschool; D005260:Female; D005865:Gestational Age; D006801:Humans; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D007608:Kainic Acid / Q000378:metabolism*; D008875:Middle Aged; D011247:Pregnancy; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism
D007608:Kainic Acid; D018092:Kainic Acid Receptors