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Published on: November 20, 2015
Postnatal age influences hypoglycemia-induced neuronal injury in the rat brain
Kathleen Ennis1, Phu V Tran, Elizabeth R Seaquist
1Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Insights
Hypoglycemia causes brain injury in developing rats, with the cerebral cortex being most vulnerable. Injury severity varies by age, with P7 rats showing no cell damage, while P14, P28, and adult rats exhibit significant neuronal injury.
Area of Science:
- Neuroscience
- Developmental Biology
- Metabolic Disorders
Background:
- Hypoglycemia, a common metabolic issue in development, can cause neuronal injury in mature brains.
- The impact of hypoglycemia on the developing brain remains poorly understood.
- Understanding age-dependent vulnerability is crucial for managing metabolic disturbances in neonates.
Purpose of the Study:
- To investigate the effects of acute hypoglycemia on regional brain injury in rats at different developmental stages.
- To characterize the vulnerability of specific brain regions (cerebral cortex, striatum, hippocampus, hypothalamus) to hypoglycemia-induced neuronal damage.
- To determine how postnatal age influences the severity and pattern of brain injury following hypoglycemia.
Main Methods:
- Rats at postnatal days 7, 14, 28, and adulthood were subjected to controlled acute hypoglycemia (blood glucose ~30 mg/dL for 210 min).
- Neuronal injury was assessed 24 hours, 72 hours, and 1 week post-hypoglycemia using Fluoro-Jade B (FJB+) staining.
- Quantitative analysis of FJB+ cells was performed in the cerebral cortex, striatum, hippocampus, and hypothalamus.
Main Results:
- Hypoglycemia induced significant neuronal injury in P14, P28, and adult rats, but not in P7 rats.
- The cerebral cortex demonstrated the highest vulnerability to injury across all affected age groups.
- P14 rats showed less severe injury compared to P28 and adult rats, and FJB+ cells were cleared by 1 week in developing rats.
Conclusions:
- Postnatal age significantly modulates the susceptibility of the rat brain to hypoglycemia-induced neuronal death.
- The developing brain exhibits region-specific vulnerabilities to metabolic insults like hypoglycemia.
- These findings highlight the critical importance of age in determining the neurotoxic effects of hypoglycemia during development.
Abstract:
Acute hypoglycemia is associated with neuronal injury in the mature human and rodent brains. Even though hypoglycemia is a common metabolic problem during development, its effects on the developing brain are not well understood. To characterize the severity of regional brain injury, postnatal day (P) 7, P14, P28 (N=20-30/age) and adult rats (N=8-12) were subjected to acute hypoglycemia of equivalent severity and duration (mean blood glucose concentration: 30.0+/-0.1 mg/dL for 210 min). Neuronal injury in the cerebral cortex, striatum, hippocampus and hypothalamus was assessed 24 h, 72 h and 1 wk later by determining the number of degenerating cells positive for Fluoro-Jade B (FJB+) in the region. Compared with age-matched control, greater number of FJB+ cells was present per brain section of P14, P28 and adult hypoglycemia groups (p<0.005, each). The cerebral cortex was more vulnerable than hippocampus and striatum at all three ages (p<0.01). Compared with P28 (131+/-21) and adult (171+/-21) rats, fewer FJB+ cells (39+/-6) per brain section were present in P14 hypoglycemic rats (p<0.01, each). Hypoglycemia was not associated with cell injury in P7 rats. FJB+ cells were absent in the hypothalamus in all four ages. Similar results were present 24 h post-hypoglycemia, whereas analysis at 1 wk demonstrated efficient clearing of FJB+ cells in the brain regions of developing rats. Varying the duration of fasting did not alter the severity of regional cell injury. These results suggest that postnatal age influences the regional vulnerability to hypoglycemia-induced neuronal death in the rat brain.
