The Mechanism Of Brain Edema Induced By Tumor Necrosis Factor-Alpha

Objective: To investigate aquaporin4 (AQP4) expression and BBB permeability after intracerebral injection of tumor necrosis factor-alpha (TNF-α) so as to explore the mechanism of brain edema induced by TNF-αin the rats.Methods: Forty-five adult SD rats, which were used to detected brain water contents and AQP4 expression were divided randomly into groups: control group ( Group A with 5 rats), normal sodium group (B Group with 20 rats), tumor necrosis factor-alpha group (C Group with 20 rats).According to the time of execution after injection, B and C were further divided into 1h group, 6h group, 24h group and 72h group (n=5 for each group). Other Forty-five adult SD rats were used detected BBB permeability. The grouping approach was the same as the former. The brain edema models were established by microinjection of TNF-αinto the cortex.We detected brain water contents by dry-wet weight method, AQP4 mRNA expression by RT-PCR and BBB permeability by EB method.Results: (1) The water content of group A was 80.28±0.62%. It reached a peak in 6h (88.84±0.29%), and down to normal levels in 72h (80.43±0.25%). The water content of group B changed in the same pattern as group C, but it was significantly lower than group C in 6 h and 24 h (p < 0.05). (2) AQP4 mRNA expression in group A and group B was weak positive (P > 0.05). The expression of AQP4 mRNA in group C was not significant in 1h (P > 0.05), increased and peaked at 6h, and maintained higher level than that in group A in 72h (P < 0.05). (3) The EB content of group A was 6.69±2.06μg/g. The content of group C began to increase in 1h, reached a peak at 6h (66.72±5.78), and was still higher than normal level in group in 72h (P < 0.05). The changing pattern of EB in group B and group C were similar, but the EB content of B were lower than C at different time points (P < 0.05). (4) There was a significantly positive correlation between AQP4 mRNA expression and BBB permeability (R=0.839, P < 0.01), in line with the trend of changes in water content.Conclusions: TNF-αmay have a function in the development, deterioration and resolution of the brain edema via up-regulating AQP4 expression and increasing BBB permeability.