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

Intrauterine growth restricted (IUGR) infants are at increased risk for neurodevelopmental deficits that suggest the hippocampus and cerebral cortex may be particularly vulnerable. Evaluate regional neurochemical profiles in IUGR and normally grown (NG) 7-day old rat pups using in vivo 1H magnetic resonance (MR) spectroscopy at 9.4 T. IUGR was induced via bilateral uterine artery ligation at gestational day 19 in pregnant Sprague-Dawley dams. MR spectra were obtained from the cerebral cortex, hippocampus and striatum at P7 in IUGR (N = 12) and NG (N = 13) rats. In the cortex, IUGR resulted in lower concentrations of phosphocreatine, glutathione, taurine, total choline, total creatine (P < 0.01) and [glutamate]/[glutamine] ratio (P < 0.05). Lower taurine concentrations were observed in the hippocampus (P < 0.01) and striatum (P < 0.05). IUGR differentially affects the neurochemical profile of the P7 rat brain regions. Persistent neurochemical changes may lead to cortex-based long-term neurodevelopmental deficits in human IUGR infants.

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

BACKGROUND: Hypoglycemia (HG) is common in intrauterine growth restricted (IUGR) neonates. In normally grown (NG) neonatal rats, acute HG causes neuronal injury in the brain; the cerebral cortex is more vulnerable than the hippocampus (HPC). We hypothesized that the IUGR brain is less vulnerable to HG-induced injury while preserving regional variation in vulnerability. METHODS: We induced IUGR via bilateral uterine artery ligation on gestational day 19 (term 22 d) rats. On postnatal day 14, insulin-induced HG of equivalent severity and duration (blood glucose < 40 mg/dl for 240 min) was produced in IUGR and NG (IUGR/HG and NG/HG). Neuronal injury in the cortex and HPC was quantified 6-72 h 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 quantitative PCR. RESULTS: There were fewer FJB-positive (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: HG-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 HG-induced neuronal injury in IUGR.