Proinflammatory Cytokines Mediated By NF-κB In PVN Contributes To Sympathoexcitation In Traumatic Brain Injury

BACKGROUND:Traumatic brain injury is one of the most common injuries in the medical treatment. Patients with severe traumatic brain injury may appear sympathetic excitement, like fervescence,high blood pressure, shortness of breath, rapid heart rate, accompanied by the increased plasma catecholamine levels and renal sympathetic activity, which aggravate illness. Many articles have reported the clinical research about sympathetic excitement after severe craniocerebral injury, but the pathophysiology of it is not yet clear. Cardiovascular research has confirmed that the regulation of sympathetic nerve induced sympathetic output increase is the important mechanism of the development of heart failure. Hypothalamic paraventricular nucleus is a vital regulatina center of neuroendocrine activity and a key area to activate central sympathetic excitement under many pathological conditions. The animal studies of sympathetic excitement have shown that the rise of inflammatory mediators in paraventricular nucleus cause the imbalance of excitatory and inhibitory neurotransmitter, which is one of the important pathophysiological basis of sympathetic activation output increase. Evidence have clearly shown inflammatory factor in the PVN can make the imbalance about the expression of GABA and glutamate, which induce the sympathetic excitement. TNF-α and IL-1β can augment the PVN neuron activity by the raised PGE2.So the sympathetic nerve excitement is closely related to the expression of inflammatory factor in PVN. Meanwhile,NF-κB of microglia cells is the vital biological molecules of regulating inflammatory factor expression in sympathetic excitement and other research areas. Activating NF-κB enters the nucleus to regulate the inflammatory factor expression. At the same time, we preliminary experimental results show that inflammatory factor levels rise in PVN of TBI rats,such as TNF-α、IL-6、IL-1β,accompanied by NF-κB of microglia cells activation. So we put forward that the NF-κB mediated PVN inflammatory reaction after craniocerebral injury may be the important pathophysiological basis of sympathetic excitement after TBI.OBJECTIVE:Establish the Craniocerebral injury rat model to observe the heart rate, mean arterial pressure, norepinephrine and TNF-α levels in PVN. Through the variation between time and index, choose the best time points to inject PDTC and PTX. Verify the degree of sympathetic excitement and test the expression quantity of TNF-a.METHOD:First, select weight between200-250g male SD rats, then randomly divided into 7 groups:establish craniocerebral injury models.Six time points for each group:3h,9h, 12h,24h,48h,72h,96h after injury and control group without craniocerebral injury. Detect the heart rate, mean arterial pressure, norepinephrine and TNF-α levels in PVN of 7 groups. Second, select weight between200-250g male SD rats, then randomly divided into 4 groups:traumatic brain injury group, traumatic brain injury+PTX intervention group,control group, control+PTX intervention group. Compare norepinephrine and TNF-a levels in PVN. Third, select weight between200-250g male SD rats, then randomly divided into 4 groups:traumatic brain injury group, traumatic brain injury+PDTC intervention group,control group, control+PDTC intervention group. Compare norepinephrine and TNF-a levels in PVN.RESULT:1, after the head injury,the mean arterial pressure, plasma norepinephrine and the levels of inflammation within the PVN fluctuating upward trend over time. The 9h、48h、72h and 96h groups have a higher mean arterial pressure than in the control group (P<0.05); The 9h、48h、72h and 96h groups have a higher plasma NA levels than in the control group (P<0.05); The 9h、48h、72h and 96h group have a higher amount of TNF-α within PVN than in the control group (P<0.05).2, TBI group has a higher TNF-α and norepinephrine levels than in the control group (p<0.05), the TBI+PTX group has a lower TNF-α and norepinephrine levels than in TBI group (p<0.05).3, TBI group has a higher TNF-α and NF-κB levels than in the control group (p <0.05), the TBI+PDTC group has a lower TNF-α and NF-κB levels than in TBI group (p<0.05).CONCLUSION:Traumatic brain injury can cause sympathetic excitement; The inflammatory factor of hypothalamus paraventricular nucleus after craniocerebral injury show a rise trend, accompanied by the changes of sympathetic nerve excitement level. There may be a certain correlation between them, TNF-α may be the main factor of sympathetic excitement regulation. In rats with traumatic brain injury, the NF-κB can regulate expression of TNF-α and adjust the excitement of sympathetic nerve. This study confirm the hypothalamus paraventricular nucleus regulate the expression of inflammatory factors when sympathetic activates. Provide reference to reveal the pathophysiological basis of the sympathetic nerve excitement after craniocerebral injury.