"While some researchers question whether hypoglycemia in infants has long-term detrimental health effects on the brain, we believe it does," says Children's Center neonatologist Jane McGowan, M.D., the paper's lead author. "Both learning and memory may be affected by any alteration of the ability of the brain to make synapses."
McGowan and her collaborators found that low blood sugar levels altered the ability of some neurotransmitter receptors to bind glutamate. These glutamate receptors are known to play an important role in the formation of synapses needed for normal brain function. McGowan suggests hypoglycemia and subsequent changes in the behavior of these glutamate receptors may affect the ability of the brain to develop normally. The causes of hypoglycemia in human infants are diverse, but it most often occurs because a mother is diabetic or if there is an interruption in the baby's own sugar storage processes.
The researchers studied two kinds of glutamate receptors, the kainate and N-methyl-D-aspartate (NMDA) receptors, so-called because each receptor specifically binds one of the two glutamate-like molecules. Kainate and NMDA are chemicals typically used to assess glutamate receptor activity in neurological experiments. Using a protocol approved by the Institutional Animal Care and Use Committee at MCP Hahnemann University, the research team sustained hypoglycemia in piglets (3 to 6 days old) for two hours with insulin injections. Researchers then extracted brain tissue from six hypoglycemic piglets and six piglets with normal blood sugar levels. After isolating brain cell membrane --- where the glutamate receptors reside --- the team performed assays to determine the ability of the NMDA and kainate receptors to bind glutamate labeled with tritium (3H).
The researchers found that NMDA receptors from brain cells bathed in low blood sugar bound more glutamate than glutamate receptors from normal brain cells. By contrast, once glutamate was bound, the NMDA receptors from hypoglycemic and non-hypoglycemic piglets both clung to their quarry with about the same strength.
McGowan cautions that the research does not, as yet, reveal whether brain damage occurs and whether changes in receptor behavior caused by hypoglycemia have long-lasting impacts. "Those questions are next," McGowan says.
Santina Zanelli, M.D., Arleen Haynes-Laing, Om Mishra, M.D., and Maria Delivoria-Papadopoulos, M.D., of St. Christopher's Hospital in Philadelphia and MCP Hahnemann University also contributed to the report. It was funded by a grant from the National Institutes of Health.
"Modification of glutamate binding sites in newborn brain during hypoglycemia" Brain Research Feb. 2002; v. 927, issue 1, pp. 80-86
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