In vivo ³¹P and in vitro ¹H nuclear magnetic resonance study of hypoglycemia during neonatal seizure

Abstract

To examine the hypothesis that hypoglycemia has an adverse effect on brain energy state during seizure, neonatal dogs were subjected to bicuculline-induced seizure while hyperglycemic, normoglycemic, or hypoglycemic. Cerebral blood flow increased and remained elevated in all animals subjected to seizure, regardless of blood or brain glucose concentration. In vivo 31P nuclear magnetic resonance spectroscopy disclosed a small (10-20%) decrease in adenosine triphosphate levels and a greater (20-40%) decline in phosphocreatine levels in animals experiencing seizure, irrespective of whether they were hyper-, normo-, or hypoglycemic. In vitro analysis of brain extracts with 1H nuclear magnetic resonance spectroscopy disclosed a significant elevation of lactate in all seizing animals. There were differences in brain alanine, glycine, and beta-hydroxybutyrate levels between the hyperglycemia-seizure and hypoglycemia-seizure groups. Alternate substrates such as lactate, fatty acids, or amino acids may be used when neonatal seizure is complicated by hypoglycemia, thereby preventing further deterioration of brain metabolic state.

Brain Injury Patterns in Hypoglycemia in Neonatal Encephalopathy

“…16 Animal models suggest increased morbidity and mortality when hypoxic-ischemic injury and neonatal hypoglycemia coexist compared with hypoxic-ischemic injury alone or isolated neonatal hypoglycemia. 12,13 A cohort of 94 term neonates with encephalopathy showed a 16% incidence of hypoglycemia, associated with increased odds for corticospinal tract injury. 22 Higher rates of hypoglycemia have been associated with greater degrees of encephalopathy, 4 yet in our cohort there was little difference between those with or without hypoglycemia.…”

“…[9][10][11] Numerous animal and human studies have suggested that neonatal hypoglycemia in the context of HIE may be more detrimental than either condition alone. [12][13][14] These studies also suggest that lower glucose levels are associated with a higher severity of encephalopathy and a worse outcome at 2 years. 4,14 Neuroimaging studies in neonatal hypoglycemia have shown a correlation between hypoglycemia, parieto-occipital injury, and involvement of the underlying white matter tracts, corpus callosum, and thalamus.…”

The Effect of Diazepam on Neonatal Seizure: In Vivo 31P and 1H NMR Study

“…The method of preparation has been recently described (6). Mongrel dogs (4-12 days old) were anesthetized with halothane, 1-4%, while undergoing tracheotomy and femoral arterial catheterization.…”

“…Anesthesia during the ictus was produced by the seizure itself which results in loss of awareness. The EEG, blood pressure, blood glucose, and blood lactate were monitored during the experiment (6). Experiments were approved by the Yale University Animal Care Committee and carried out with the adherence to "Guiding Principles for the Care of Animals," of the American Physiological Society, and in accordance with federal regulations.…”

“…In vivo "P data were collected using a 2.0 Tesla, 3 1-cm bore diameter superconducting magnet (General Electric CSI 11, (CSI 11; General Electric, Fremont, CA) and a 2-cm circular transmitter-receiver surface coil tuned for phosphorus (34.5 MHz, 512 acquisitions, repetition rate, 1.0 s). Reflection of cranial muscle was not done because previous imaging studies (6) show that most of the signal is derived from the relatively large brain of the neonatal dog. Moreover, the PCr/ P, ratio in the control state was near unity, indicating minimal contamination from surrounding muscle (7).…”