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Published on: November 20, 2015
Acute hypoglycemia results in reduced cortical neuronal injury in the developing IUGR rat
Anne M Maliszewski-Hall1, Ariel B Stein1, Michelle Alexander1
1Department of Pediatrics, Division of Neonatology, University of Minnesota, Minneapolis, MN, USA.
Insights
Hypoglycemia causes less brain injury in growth-restricted neonates. Adaptations like lower body temperature and increased MCT2 may offer neuroprotection in intrauterine growth restriction (IUGR) brains during hypoglycemia (HG).
Area of Science:
- Neuroscience
- Neonatal Research
- Developmental Biology
Background:
- Hypoglycemia (HG) is prevalent in intrauterine growth restricted (IUGR) neonates.
- Acute HG injures neurons in normally grown (NG) neonatal rat brains, with the cortex being more vulnerable than the hippocampus (HPC).
- This study investigates if the IUGR brain exhibits reduced vulnerability to HG-induced injury while maintaining regional differences.
Purpose of the Study:
- To determine if the IUGR brain is less vulnerable to hypoglycemia-induced neuronal injury compared to normally grown brains.
- To examine the regional vulnerability (cortex vs. hippocampus) in IUGR neonates under hypoglycemic conditions.
- To explore potential protective mechanisms, including transporter expression, in the IUGR brain during hypoglycemia.
Main Methods:
- Intrauterine growth restriction (IUGR) was induced in rats via uterine artery ligation.
- Insulin-induced hypoglycemia (HG) was administered to IUGR and NG rats on postnatal day 14.
- Neuronal injury was quantified using Fluoro-Jade B (FJB) histochemistry, and mRNA expression of MCT1, MCT2, GLUT1, and GLUT3 was analyzed via quantitative PCR.
Main Results:
- Fewer FJB-positive cells (indicating neuronal injury) were observed in the cortex of IUGR/HG rats compared to NG/HG rats.
- No significant difference in FJB-positive cells was found in the hippocampus between IUGR/HG and NG/HG groups.
- IUGR/HG rats exhibited lower core body temperature, and increased MCT2 expression was noted in the IUGR cortex.
Conclusions:
- The developing IUGR brain shows decreased cortical neuronal injury during hypoglycemia.
- Systemic hypothermia and enhanced delivery of alternative substrates via MCT2 are potential protective adaptations against HG-induced neuronal injury in IUGR.
- These findings suggest specific neuroprotective strategies in IUGR neonates facing hypoglycemia.
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.
