The role of TNF-α, IL-6, IL-10, and GDNF in neuronal apoptosis in neonatal rat with hypoxic-ischemic encephalopathy.
OBJECTIVE
To examine the dynamic changes of TNF-α, IL-6, IL-10, and GDNF (glial cell-derived neurotrophic factor) in serum or brain tissues of neonatal rat with hypoxic-ischemic encephalopathy and to explore their roles in neuronal apoptosis.


METHODS
A total of 80 Wistar rats were randomly divided into the sham-operated (control) group and the hypoxia-ischemia (HI) group. To establish the hypoxic-ischemic encephalopathy (HIE) model, the pups from the HI group were subjected to left common carotid artery ligation followed by exposure to 8% O2 and 92% N2. The concentration of TNF-α, IL-6, IL-10, and GDNF in serum or brain tissues was measured by enzyme linked immunosorbent assay (ELISA). Neuronal apoptosis was examined by flow cytometry (FC). Statistical analysis was performed using the SPSS13.0 software.


RESULTS
We found that the neuronal apoptosis rate and the levels of TNF-α and IL-6 in rat with hypoxic-ischemic brain damage (HIBD) were significantly increased at 6 h, 24 h, 48 h, and 72 h after hypoxia compared to the control group (p < 0.05). We also found that the neuronal apoptosis rate was positively correlated with the levels of TNF-α and IL-6, and negatively correlated with IL-10 and GDNF.


CONCLUSIONS
In neonatal rats with HIE, the brain reaches its peak levels of damage by 24~72 h after the injury. Inflammatory cytokines such as TNF-α and IL-6 promote HIE-induced neuronal apoptosis, whereas IL-10 and GDNF antagonize it.
S-J
SJ
Li
W
W
Liu
J-L
JL
Wang
Y
Y
Zhang
D-J
DJ
Zhao
T-J
TJ
Wang
Y-Y
YY
Li
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10