Abstract:

Objective   To establish a reliable animal model of brain injury induced by neonatal hypoglycemia and observe the  corresponding neurodegeneration in different brain regions of neonatal rats. Methods    Newborn Wistar rats were randomly divided into: insulin-treated rats with short hypoglycemia (INS-S group, n=40), insulintreated rats with prolonged hypoglycemia (INS-P group, n=40), fasting rats (FAS group, n=40) or control rats (CON group, n=40). Neonatal hypoglycemia was produced by fasting or insulin injections (15U/kg, hypodermic injection) on postnatal day 2 (P2), 4 (P4), and 6 (P6). Double labeled immunofluorescent with neuronal nuclear protein (NeuN) and FJB was performed to examine the neuronal degeneration in the rat brain 2h, 6h, 1d, 3d, 7d and 14d after the third hypoglycemic insult. Results   No FJB+ cells were detected in INS-S, FAS and CON rats at any designated time point, but numerous FJB+ cells were detected in INSP rats at 6h, 1d, 3d and 7d after the third hypoglycemic insult. Double labeled immunofluorescent with NeuN showed these FJB+ cells all presented NeuN immunoreactivity. There were numerous FJB+ cells in the parasagittal cortex, piriform cortex, hypothalamus, thalamus and dentate gyrus. Conclusion    Insulin hypodermic injections in newborn rat can establish a reliable animal model of brain injury damaged by neonatal hypoglycemia. Repetitive and profound neonatal hypoglycemia can result in extensive neurodegeneration, in which the neurons of the cortex, thalamus, hypothalamus and dentate gyrus are more vulnerable.

Key words: Hypoglycemia; Model, animal; Fluoro-Jade B staining; Neuron; Rat, Wistar; Neonate