ACUTE HYPOGLYCEMIA RESULTS IN REDUCED CORTICAL NEURONAL INJURY IN THE DEVELOPING IUGR RAT

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.