Postnatal age influences hypoglycemia-induced neuronal injury in the rat brain.
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.
Ennis
Kathleen
K
Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Tran
Phu V
PV
Seaquist
Elizabeth R
ER
Rao
Raghavendra
R
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005452:Fluoresceins; D005508:Food Deprivation / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007003:Hypoglycemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009930:Organic Chemicals; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D013217:Starvation / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
D005452:Fluoresceins; D007328:Insulin; D009930:Organic Chemicals; C435731:fluoro jade; D005947:Glucose