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Changes of Inflammatory Cytokines and Neurotrophins Emphasized Their Roles in Hypoxic-Ischemic Brain Damage.

Authors: Wang, Y  Cao, M  Liu, A  Di, W  Zhao, F  Tian, Y  Jia, J 
Citation: Wang Y, etal., Int J Neurosci. 2012 Dec 7.
Pubmed: (View Article at PubMed) PMID:23110519
DOI: Full-text: DOI:10.3109/00207454.2012.744755

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-alpha), intercellular adhesion molecule-1 (ICAM-1), interleukin 1beta (IL-1beta), 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% O(2) and 92% N(2) 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-alpha, ICAM-1, IL-1beta, 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-alpha, ICAM-1, IL-1beta, 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-alpha, ICAM-1, and IL-1beta 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-alpha, ICAM-1, and IL-1beta contribute to neuronal apoptosis induced by HIBD, whereas neurotrophins NGF and BDNF antagonize it.

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RGD Object Information
RGD ID: 7204438
Created: 2012-12-18
Species: All species
Last Modified: 2012-12-18
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.