European Journal of Pediatrics

, 167:1169 | Cite as

Repetitive and profound insulin-induced hypoglycemia results in brain damage in newborn rats: an approach to establish an animal model of brain injury induced by neonatal hypoglycemia

  • Dong Zhou
  • Jing Qian
  • Chun-Xi Liu
  • Hong Chang
  • Ruo-Peng Sun
Original Paper

Abstract

The human neonate is at a higher risk for hypoglycemia-induced neuronal injury than other pediatric and adult patients. Repetitive and profound neonatal hypoglycemia can result in severe neurologic sequelae, of which the mechanisms was not elucidated by hitherto. Moreover, no reliable animal model of brain injury induced by neonatal hypoglycemia is available in order to carry out more research. Therefore, we tried to induce neonatal hypoglycemia in newborn rats by fasting and insulin injection, and then examined the neuronal degeneration after repetitive hypoglycemic insults by Fluoro-Jade B (FJB) staining. Experimental animals were randomly divided into four groups: insulin-treated rats with short hypoglycemia, insulin-treated rats with prolonged hypoglycemia, fasted rats, and control rats. Insulin injection and fasting both could induce consistent hypoglycemia in newborn rats. But from FJB staining results, only in insulin-treated rats with prolonged hypoglycemia could extensive neurodegeneration be detected. We can conclude that FJB staining is a useful method of marking neuronal degeneration in neonatal rats following hypoglycemic brain damage. Repetitive and profound neonatal hypoglycemia can result in extensive neurodegeneration, and it seems that neurons of the cortex, dentate gyrus of the hippocampus, the thalamus, and the hypothalamus are more vulnerable to hypoglycemic insult in newborn rats. Repetitive and profound insulin-induced hypoglycemia in newborn rats can establish a reliable animal model of brain injury resulting from neonatal hypoglycemia.

Keywords

Neonate Hypoglycemia Fluoro-Jade B staining Neuron 

Abbreviations

CA1

CA1 region of the hippocampus

CA3

CA3 region of the hippocampus

CON

Control rats

DG

Dentate gyrus of the hippocampus

FAS

Fasted rats

FJB

Fluoro-Jade B

h.i.

Hypodermic injection

INS-P

Insulin-treated rats with prolonged hypoglycemia

INS-S

Insulin-treated rats with short hypoglycemia

P

Postnatal day

PBS

Phosphate-buffered saline

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Dong Zhou
    • 1
  • Jing Qian
    • 1
  • Chun-Xi Liu
    • 2
  • Hong Chang
    • 3
  • Ruo-Peng Sun
    • 1
  1. 1.Department of PediatricsQilu Hospital of Shandong UniversityShandongChina
  2. 2.The Key Laboratory of Cardiovascular Remodeling and Function ResearchChinese Ministry of Education and Chinese Ministry of HealthShandongChina
  3. 3.Department of PediatricsMedicine School Hospital of Qingdao UniversityShandongChina

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