Acute hypoglycemia results in reduced cortical neuronal injury in the developing IUGR rat

Abstract

Background Hypoglycemia (HG) is common in IUGR neonates. In normally grown (NG) neonatal rats, acute HG causes neuronal injury in the brain, cerebral cortex more vulnerable than the hippocampus (HPC). We hypothesized that the IUGR brain is less vulnerable to hypoglycemia-induced injury while preserving the regional variation in vulnerability. Methods We induced IUGR via bilateral uterine artery ligation on gestational day 19 (term 22d) rats. On postnatal day 14, insulin-induced HG of equivalent severity and duration (blood glucose <40mg/dl for 240 min) was produced in IUGR and NG (IUGR/HG and NG/HG) groups. Neuronal injury in the cortex and HPC was quantified 6-72 hr later using Fluoro-Jade B (FJB) histochemistry. The mRNA expression of monocarboxylate transporters, MCT1 and MCT2, and glucose transporters, GLUT1, and GLUT3 was determined using qPCR. Results There were fewer FJB+ cells in the cortex of IUGR/HG; no difference was observed in FJB+ cells in HPC. Core body temperature was lower in IUGR/HG compared with NG/HG. MCT2 expression was increased in the IUGR cortex. Conclusion Hypoglycemia-induced neuronal injury is decreased in the cortex of the developing IUGR brain. Adaptations including systemic hypothermia and enhanced delivery of alternative substrates via MCT2 might protect against hypoglycemia-induced neuronal injury in IUGR.

Differential Effects of Intrauterine Growth Restriction on the Regional Neurochemical Profile of the Developing Rat Brain

“…On G19 (term = 22.5 days), pregnant rats were anesthetized with inhaled isoflurane (1.5%–3%) in a 50:50 mixture of N 2 O and O 2 . To induce fetal IUGR, a mid-line incision was made along the abdomen, the uterus was exposed and both uterine arteries were ligated (14,15). Normally grown (NG) control animals did not undergo surgery.…”

“…We hypothesized that IUGR will negatively affect metabolic markers of energy metabolism, neurotransmission and myelination in the cerebral cortex and hippocampus while sparing the striatum. We used a well-described surgical model of IUGR that results in a 20–25% reduction in birth weight (14,15). Rat pups at postnatal (P) day 7 were studied due to their neurodevelopmental similarity to human near-term infants (16).…”

Intrauterine Growth Restriction: Hungry for an Answer

“…For example, acute hypoglycemia induced by insulin infusion in IUGR rats (due to bilateral uterine artery ligation) results in neuronal injury of the brain cortex but to a lesser degree than the injury encountered in response to insulininduced hypoglycemia in normally grown neonatal rats. No difference in brain GLUT1 or GLUT3 mRNA expression was evident between groups (87). Therefore, the IUGR rat pups are relatively protected against acute hypoglycemic neuronal injury.…”