Alpha Lipoic Acid For Traumatic Epilepsy Rat Brain Protective Effects And Its Mechanism

Objective:Epilepsy is a chronic neurological disorder,with the characteristics of transient,rigidity,attacks began and ended abruptly.Traumatic brain injury(TBI)is one of the causes of symptomatic epilepsy.Epileptic seizures caused by cerebral ischemia and hypoxia damage the brain neurons,produce a large number of free radicals,causes mitochondrial damage.Then the apoptosis and necrosis which caused by mitochondria dysfunction,leads to more severe seizures.In this study,we investigated the changes of mitochondria and oxidative stress in the rat model of posttraumatic epilepsy(PTE).The changes of mitochondrial function in posttraumatic epilepsy were investigated by detecting the expression of apoptosis and related apoptosis protein.The effects of neuronal apoptosis and ultrastructural damage on the pathogenesis of posttraumatic epilepsy and the effects of antioxidants on the pathologic remodeling process were further explored by using the changes of α-lipoic acid(α-LA).Methods: 45 male wistar rats were randomly divided into three groups(normal control group,traumatic epilepsy group and α-LA group),15 rats in each group.A dose of Fe Cl2 was injected into rats to establish the model of posttraumatic epilepsy.Implanted stainless steel electrodes according to the stereo atlas,the EEG of rats in each group were recorded.In order to detecte the changes of never tissue morphology and apoptotic cells in PTE rats,we observed cortical neurons of rats by Nissl staining,detected and analysed of Caspase-3 protein by Western-Blot method,and observed the contents of malonaldehyde(MDA)and nitric oxide(NO)in mitochondria,detected Na+-K+-ATP enzyme,Ca2+-Mg2+-ATP enzyme,total ATP enzyme,superoxide dismutase(SOD),glutathione peroxidase enzyme(GSH-Px)activity and the changes of mitochondrial membrane potential.Results:(1)Normal control rats cortex electrodes EEG were no cluster spike,PTE group cortex electrodes EEG were tracings to cluster spikes.After the intervention of α-LA,the phenomenon of cluster spike discharge was significantly improved.(2)Epileptic seizures occurred in rats of PTE group.Performance for the following symptoms:(1)ear,facial spasm tic,including blinking,moving beards,rhythmic chewing,ears fibrillation;(2)the whole body trembling,rhythmic nodding;(3)animal forelimb convulsive fits,the frequency with time increases;(4)double forelimb lift,semi-upright position,followed by the body and limbs,muscle clonus,not erect,falls backward;(5)animal limbs twitching,loss of postural control,generalized tonic-clonic seizures.Press Racine grade reached moderate and severe attack.After seizure,the rats were in a state of malaise,activity and reduced food intake.Control group without seizures,while seizure in the intervention group reduced significantly.(3)On the cerebral cortex and hippocampus of rats were Nissl stained hippocampus ultrastructure of pyramidal cells in PTE group changed significantly,the performance of deformed nuclei,pyknosis,in the inner surface of the nuclear membrane,chromatin condensation and broken broke into pieces near the nuclear membrane,forming a plurality of relatively dense plaques,nuclear membrane is not clear;the α-LA group were normal neuronal morphology,nuclear membrane substantially clear,no chromatin aggregation;a little blank intracytoplasmic edema Area.(4)Na+-K+-ATPase,Ca2+-Mg2+-ATPase,total ATPase activity in PTE group showed a significant decline comparing to the control group,while the α-LA group were significantly improved,there was a statistically significant difference between the two groups.Mitochondrial membrane potential in PTE group had significantly decreased,by intervening,access is possible to suppress the decline of the phenomenon.(5)SOD and GSH-PX reduced in the PTE group,MDA and NO were rising,confirmed the presence of oxidative stress in seizure.These indicators had significantly improved in the α-LA group,there were significant statistical differences between the two.(6)In PTE group,the apoptosis was significantly increased,the expression of Caspase-3 was up-regulated,while the expression of Caspase-3 was also decreased in the α-LA group.Conclusion:(1)In the PTE animal model which was established by injecting Fe Cl2 into the cerebral cortex,MDA,NO levels were significantly increased,Na+-K+-ATP enzyme,Ca2+-Mg2+-ATP enzyme,total ATP enzyme,SOD,GSH-Px significantly decreased viability;Suggesting that in the PTE rat model of mitochondria in the brain produced a lot of free radicals,and the oxidative stress injury of the brain cells was caused by the oxidative stress.The energy supply in the mitochondria of the brain cells was hindered.(2)α-LA has protective effect on mitochondrial oxidative stress injury in PTE rats.The mechanism may be related to the improvement of the activity of enzymes involved in the oxidation of mitochondria in brain tissue,and the decrease of lipid peroxidation level in mitochondrial biofilm.(3)In PTE rats,oxidative stress induced neuronal apoptosis and altered the ultrastructure of neurons.One of the ways in which α-LA protects is to inhibit oxidative stress-induced neuronal apoptosis.