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Changes of inflammatory cytokines and neurotrophins emphasized their roles in hypoxic-ischemic brain damage.

Abstract
Inflammatory cytokines and neurotrophins play crucial roles in hypoxic-ischemic brain damage (HIBD), but the expression changes of these proteins had not been systematically studied. In this article, we compared the levels of tumor necrosis factor alpha (TNF-α), intercellular adhesion molecule-1 (ICAM-1), interleukin 1beta (IL-1β), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) in the progression of HIBD and analyzed their correlations with apoptosis. Seven-day-old pups of Sprague Dawley rats (n = 120) were randomly divided into two groups: the sham-operated (control) group and the hypoxia-ischemia (HI) group. To establish the hypoxic-ischemic encephalopathy model, the pups from the HI group were subjected to left common carotid artery ligation followed by exposure to 8% O2 and 92% N2 for 2.5 hr. Pups from both the groups were sacrificed at 6, 24, 48, 72 hr and 7 days after hypoxia. The levels of TNF-α, ICAM-1, IL-1β, NGF, and BDNF in the brain tissues were measured by enzyme-linked immunosorbent assay. The neuronal apoptosis was examined by flow cytometry. We found that the levels of TNF-α, ICAM-1, IL-1β, NGF, BDNF, and neuronal apoptosis rate in neonatal rats with HIBD significantly increased at 6, 24, 48, and 72 hr after hypoxia compared to the control group (p < .05) and returned back to normal by 7 days. Furthermore, neuronal apoptosis rate was positively correlated with the levels of TNF-α, ICAM-1, and IL-1β and negatively correlated with the levels of NGF and BDNF. In neonatal rats with HIBD, the brain reaches its peak levels of damage by 24-72 hr after the injury. Inflammatory cytokines such as TNF-α, ICAM-1, and IL-1β contribute to neuronal apoptosis induced by HIBD, whereas neurotrophins NGF and BDNF antagonize it.
AuthorsYun Wang, Meng Cao, Aiqin Liu, Wenyu Di, Fen Zhao, Yunjiao Tian, Jianwei Jia
JournalThe International journal of neuroscience (Int J Neurosci) Vol. 123 Issue 3 Pg. 191-5 (Mar 2013) ISSN: 1563-5279 [Electronic] England
PMID23110519 (Publication Type: Journal Article)
Chemical References
  • Cytokines
  • Inflammation Mediators
  • Nerve Growth Factors
Topics
  • Animals
  • Animals, Newborn
  • Cytokines (physiology)
  • Hypoxia, Brain (metabolism, pathology)
  • Hypoxia-Ischemia, Brain (metabolism, pathology)
  • Inflammation Mediators (physiology)
  • Nerve Growth Factors (physiology)
  • Rats
  • Rats, Sprague-Dawley

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