Long-term losses of amygdala corticotropin-releasing factor neurons are associated with behavioural outcomes following neonatal hypoxia-ischemia

Behav Brain Res. 2010 Apr 2;208(2):609-18. doi: 10.1016/j.bbr.2010.01.007. Epub 2010 Jan 18.


Neuronal losses are observed in the brain after neonatal hypoxia-ischemia (HI) however few studies have examined the effects of HI on specific neuronal phenotypes and their possible contribution to behavioural outcomes. In the present study we examined whether postnatal day 3 (P3) HI alters numbers of corticotropin-releasing factor (CRF) and neuropeptide-Y (NPY) neurons in the paraventricular nucleus of the hypothalamus (PVN), the bed nucleus of the stria terminalis (BNST) and the amygdala, 1 (P10) and 6 (P45) weeks after P3 HI. A significant reduction in the number of CRF-positive neurons in the PVN, central nucleus of the amygdala (CeA) and BNST ipsilateral to the carotid ligation 1 and 6 weeks after P3 HI was observed. There was also a significant reduction in the number of NPY-positive neurons in the PVN, amygdala and BNST ipsilateral to the carotid ligation 1 week after P3 HI. However after 6 weeks, only the number of PVN NPY-positive neurons decreased significantly. At 6 weeks post-insult, the number of CeA CRF-positive neurons was inversely associated with locomotor activity and exploratory behaviour in an open field. In contrast, no significant correlations between neuronal counts and early neurodevelopment tests performed on P10 were observed. Thus after P3 HI persistent losses of CRF- and NPY-positive neurons occur and the loss of CeA CRF neurons may provide a central anatomical mechanism underlying neurobehavioural deficits observed 6 weeks after P3 HI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / pathology*
  • Animals
  • Animals, Newborn
  • Behavior, Animal
  • Cell Count / methods
  • Corticotropin-Releasing Hormone / metabolism*
  • Exploratory Behavior / physiology
  • Gene Expression Regulation, Developmental / physiology
  • Hypoxia-Ischemia, Brain / pathology*
  • Hypoxia-Ischemia, Brain / physiopathology
  • Neurons / metabolism*
  • Neuropeptide Y / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reflex / physiology
  • Statistics as Topic


  • Neuropeptide Y
  • Corticotropin-Releasing Hormone