Neuroprotective Effect Of Valproic Acid On Patients With Acute Severe Brain Injury

BackgroundTraumatic brain injury(TBI)is a common surgical disease in clinic,which has the characteristics of high incidence,high mortality and poor prognosis.TBI can be divided into primary and secondary traumatic brain injury.Primary traumatic brain injury occurs immediately after injury and produces corresponding clinical symptoms.The treatment is relatively difficult.Secondary traumatic brain injury occurs after brain injury,which mainly involves the process of calcium overload,the release of inflammatory factors,and the abnormal apoptosis of neural cells.Therefore,it has become an important breakthrough in the treatment of brain injury."The guidelines for the diagnosis and treatment of severe craniocerebral injury(Fourth Edition)" put forward that the incidence of clinical traumatic epilepsy of severe traumatic brain injury(sTBI)was 12%,while the use of EEG detection of subclinical seizures in patients with high proportion of 20%-25%.Therefore,acute severe brain injury(ASBI)should be routinely given to prevent traumatic seizures.At present,the first-line drugs for the prevention of traumatic epilepsy are mainly phenytoin(PHT)and valproic acid(VPA)and so on.As two kinds of commonly used antiepileptic drugs in clinical,the effective ingredients of sodium valproate and phenytoin sodium are VPA and PHT."Guidelines for the prevention and treatment of epilepsy after surgery and trauma in Department of Neurosurgery"(Draft)recommend that VPA and PHT can be routinely applied to prevent traumatic epilepsy.Clinical studies have shown that the overall incidence of epilepsy following the use of VPA and PHT in prevention of posttraumatic epilepsy is similar.In recent years,animal model experiments have shown that VPA has a significant effect in the treatment of stroke,brain injury,spinal cord injury and so on.Through the clinical study of brain injury,Elizabeth thought it was clear that PHT can effectively prevent traumatic epilepsy.But there was no statistical significance in improving cognitive dysfunction and other neurological protection.ObjectiveTo observe the changes of serum IL-6 and NSE levels in patients with ASBI after 14 days of injury.To observe the effect of VPA on the recovery of neurological function in patients with ASBI.To explore the neuroprotective effect of VPA on ASBI.MethodsA prospective randomized controlled trial was carried out in First Affiliated Hospital of Xinxiang Medical College from January 2015 to August 2016,92 patients with acute severe brain injury were treated in this study.Among them,there were no deaths during the treatment period,and the total number of patients was not matched in the treatment period,and the total number of cases was 2 cases in the treatment of the patients in the treatment group(88 cases).Consecutive 88 patients with acute severe traumatic brain injury were randomly divided into two groups,namely observation group(given sodium valproate in the conventional treatment,45 cases)and control group(routine treatment given phenytoin sodium,43 cases).The venous blood of two groups of patients with traumatic brain injury on the 1,2,3,7,14 d were collected to detect the NSE and IL-6 levels.The GCS scores of the patients in the two groups were performed before treatment and on the 7,14 and 21 d after treatment.The GOS score was performed between 1month and 3 months after treatment.On the 21 d after treatment,the National Institutes of Health Stroke Scale(NIHSS)score was used to evaluate the neurological deficits of the patients in the two groups and the Barthel index(BI)was used to evaluate the patients' ability of daily living.ResultsThe two groups of patients with serum IL-6 and NSE concentration in 1d after injury are increasing rapidly,the concentration of IL-6 reached the peak on the 2d.The concentration of IL-6 showed a downward trend on the 3d,7d.The concentration of IL-6 on the 14 d increased compared with on the 7d.The concentration of NSE showed the first peak on the 2d.The NSE concentration showed a downward trend on the 3d.The concentration increased and reached the highest peak on the 7d.The concentration decreased on the 14 d.The same time points were lower than the normal control group.The difference of 1d was not statistically significant.The difference of concentration on the 2,3,7,14 d was statistically significant.In the observation group after treatment,The GCS score compared with the control group on the 7,14 d was not statistically significant(P > 0.05).On the 21 d after the treatment of the observation group GCS scores were significantly better than the control group(P < 0.05).The observation group of patients after treatment for 1 month and the follow-up 3 months after treatment of the GOS score was significantly better than the control group(P < 0.05).Before treatment,two groups of patients of the NIHSS score and Barthel index was not statistically significant(P > 0.05).After treatment,the NIHSS score and the Barthel index of the two groups on the 21 d were significantly improve than those before treatment(P < 0.05).The observation group was significantly better than the control group(P < 0.05).ConclusionVPA can improve the neurological deficits in patients with ASBI.The mechanism may be that it can inhibit the IL-6 induced inflammatory cascade and reduce the abnormal apoptosis of neurons to reduce the release of NSE.