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

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.