NUCLEAR FACTOR KAPPA B REGULATES SYMPATHETIC NERVE EXCITABILITY FOLLOWING A HEAD INJURY BY INFLUENCING THE EXPRESSION OF TUMOR NECROSIS FACTOR ALPHA

Kai Wang^#, Li Wang^#, Shuang Wu, and Lei Zhang^*

Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi’an, 710032, China

Objective: We sought to analyze whether nuclear transcription factor kappa B (NF-κB) regulates sympathetic nerve excitability after brain injury by adjusting the expression of tumor necrosis factor alpha (TNF-α). 

Methods: Sixty clean-grade healthy male Sprague–Dawley rats were randomly selected to establish a rat model of sympathetic nerve excitability following a head injury. Thirty rats were randomly selected and stratified into a sham operation group and model group, respectively, with five rats in the sham operation group and 25 rats in the model group. At three, nine, 24, 48, and 72 hours after modeling (where rats were divided into five subgroups at each time point, with five rats in each group), changes in the mean arterial pressure, heart rate, plasma norepinephrine level, and expression level of TNF-α in the paraventricular nucleus of the hypothalamus were measured. The rat brain tissue was fetched and pathological changes in the rat brain tissue in each group were measured. Fifteen rats were randomly selected and divided into a sham operation group, a model group, and a TNF-α–inhibition group, respectively, with five rats included in each group. Among them, rats in the TNF-α–inhibition group were given the TNF-α inhibitor pentoxifylline at 40 μL/h; then, the expression level of TNF-α in paraventricular nucleus tissue from the hypothalamus and the change in plasma norepinephrine level in each group were determined. The remaining 15 rats were randomly divided into a sham operation group, a model group, and an NF-κB–inhibition group, with five rats included in each group; rats in the NF-κB inhibition group were given the NF-κB inhibitor pyrrolidine dithiocarbamate at 150 mg/d. The expression levels of NF-κB and TNF-α in the paraventricular nucleus of the hypothalamus were determined in each group. 

Results: The average arterial pressure, heart rate, plasma norepinephrine level, and TNF-α expression level in hypothalamic paraventricular nucleus tissue from rats in the sham operation group were not statistically different at each time point (P>0.05). In the model group, compared with at three hours, the mean arterial pressure, plasma norepinephrine level, and TNF-α expression in paraventricular nucleus tissue from the hypothalamus were increased significantly at nine hours, while the heart rate was decreased significantly (P<0.05); further, starting after 24 hours, as more time elapsed, the levels of the above indicators gradually increased. The brain tissue of rats in the sham operation group showed regular shape, clear structure, and neatly arranged nerve fibers; in contrast, the brain tissues of rats in the model group were more traumatized, neurons were disintegrated and degenerated, and edema to a certain degree was observed. Compared with in the sham operation group, the expression levels of TNF-α, NF-κB, and plasma norepinephrine in hypothalamic paraventricular nucleus tissue from the model group were significantly increased (P<0.05); separately, compared with in the model group, the expression levels of TNF-α, NF-κB, and plasma norepinephrine in paraventricular nucleus tissue from the hypothalamus in the TNF-α–inhibition group and the NF-κB inhibition group were significantly reduced (P<0.05). 

Conclusion: Craniocerebral injury can cause sympathetic nerve excitement, and there is an obvious inflammatory response; NF-κB may regulate the sympathetic nerve excitability by influencing the level of TNF-α.