| Background Traumatic brain injury(traumatic brain injury,TBI)is very common in Department of Neurosurgery,Traumatic brain injury(TBI)initiates a complex series of neurochemical and signaling changes that lead to pathological events including neuronal hyperactivity,excessive glutamate release,inflammation,increased blood-brain barrier(BBB)permeability and cerebral edema,altered gene expression,and neuronal function dysfunction,have a great impact on the prognosis of patients,bring the dual pressure of the body and the economy.At present,there is no exact medication and treatment to deal with the secondary injury after brain injury.At present,the focus of the study is focused on the protection of nerve cells after brain injury and the injury of inflammatory response to brain tissue.Valproic acid(valproic acid,VPA),a histone deacetylase inhibitor,has been used in clinical practice,and its neuroprotective effect is multifaceted.This study using rat brain injury blow to establish closed craniocerebral injury model rats,and given valproate,the changes at different time points in rats behavioral assessment and magnetic resonance imaging,acetylation of histone H3,NF-?B expression,to investigate the anti-inflammatory mechanism of VPA,and provide a reliable basis for clinical application of VPA in TBI.Objective In order to investigate the effect of valproic acid on inflammatory response in rats with experimental brain injury,the effects of VPA on the expression of acetylated histone H3 and NF-?B protein in brain tissue of rats with TBI at different time points were observed.Methods 75 male SD rats were divided into 3 groups according to the random principle: sham operation group,injury group and VPA treated group.The traumatic brain injury and valproic acid established rat model of closed head injury.The sham operation group were just cut the scale and sutured on the same place.The VPA treatment group was injected with VPA into abdominal cavity by 300 mg/kg every day,the same day as the day of the death,and the simple injury group and sham operation group were injected with the same volume of normal saline at the same time.Behavioral evaluation of rats at different time points after injury.The rats of each group(n=5)were killed at 6 h,24 h,48 h,72 h after injury.The activation of nuclear factor kappa B(NF-?B)was examined by fluorescence double-labeling staining technique and laser scanning confocal microscope.The expression of acetylated histone was detected with immunohistochemistry,the rat of each group(n=1)was chosen at 72 h after injury injected intraperitoneally with chloral hydrate,and the magnetic resonance imaging was performed at the National Center of Beijing.Results 1.Behavioral scoring results: In giving the intervention of VPA,compared with VPA rats and TBI rats injury was alleviated,but there is no obvious effect in 24 h after injury,there was no significant difference between the 3 groups(P>0.05);7 d and 14 d,after the intervention,motor,sensory and reflex function in VPA treated rats,were significantly better than group TBI,the difference was statistically significant between the two groups(P<0.05).2.7.0T small animal magnetic resonance imaging detection: The single injury group were close to the red color compared with the normal control group,indicating the degree of edema was more serious,the damage range is yellow,indicating the most severe edema,VPA treatment group and injury group compared to the lesions of color close to the blue,in the injured brain tissue edema in rats after treatment with VPAreduced.It can be seen from the figure that the brain tissue volume in the VPA treatment group was significantly lower than that of the single injury group at the same time point,indicating that VPA can reduce the volume of brain injury.3.Immunohistochemical detection: The expression level of histone H3 in the 3 groups was statistically significant(P<0.05),there was no significant difference between VPA group and C group,TBI group was significantly lower than that in group C(P<0.05).4.Immunofluorescence: C group of rat brain tissue each time slice NF-?B nuclear positive cells expressed little or no expression,compared with the C group,after the injury number of 6 h TBI group and VPA group rat brain tissue sections of NF-?B nuclear positive cells were higher than that of group C,24 h in rat brain tissue sections of NF-?B nuclear positive the number of cells was significantly higher than that of group C,48 h and 72 h NF-?B nuclear positive cells began to decrease,but still higher than the high expression of C group(P<0.05);VPA group NF-?B nuclear positive cells at each time point expression were lower than those in group TBI(P<0.05).Conclusions Valproic acid on the anti-inflammatory action of rats after traumatic brain injury may be by inhibiting the NF-?B activation. |
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