Pathogenesis Of Post-traumatic Epilepsy Research Articles

Exploring the pathogenesis linking traumatic brain injury and epilepsy via bioinformatic analyses.

Traumatic brain injury (TBI) is a serious disease that could increase the risk of epilepsy. The purpose of this article is to explore the common molecular mechanism in TBI and epilepsy with the aim of providing a theoretical basis for the prevention and treatment of post-traumatic epilepsy (PTE). Two datasets of TBI and epilepsy in the Gene Expression Omnibus (GEO) database were downloaded. Functional enrichment analysis, protein-protein interaction (PPI) network construction, and hub gene identification were performed based on the cross-talk genes of aforementioned two diseases. Another dataset was used to validate these hub genes. Moreover, the abundance of infiltrating immune cells was evaluated through Immune Cell Abundance Identifier (ImmuCellAI). The common microRNAs (miRNAs) between TBI and epilepsy were acquired via the Human microRNA Disease Database (HMDD). The overlapped genes in cross-talk genes and target genes predicted through the TargetScan were obtained to construct the common miRNAs-mRNAs network. A total of 106 cross-talk genes were screened out, including 37 upregulated and 69 downregulated genes. Through the enrichment analyses, we showed that the terms about cytokine and immunity were enriched many times, particularly interferon gamma signaling pathway. Four critical hub genes were screened out for co-expression analysis. The miRNA-mRNA network revealed that three miRNAs may affect the shared interferon-induced genes, which might have essential roles in PTE. Our study showed the potential role of interferon gamma signaling pathway in pathogenesis of PTE, which may provide a promising target for future therapeutic interventions.

Blood-Brain Barrier Breakdown Following Traumatic Brain Injury: A Possible Role in Posttraumatic Epilepsy

Recent animal experiments indicate a critical role for opening of the blood-brain barrier (BBB) in the pathogenesis of post-traumatic epilepsy (PTE). This study aimed to investigate the frequency, extent, and functional correlates of BBB disruption in epileptic patients following mild traumatic brain injury (TBI). Thirty-seven TBI patients were included in this study, 19 of whom suffered from PTE. All underwent electroencephalographic (EEG) recordings and brain magnetic resonance imaging (bMRI). bMRIs were evaluated for BBB disruption using novel quantitative techniques. Cortical dysfunction was localized using standardized low-resolution brain electromagnetic tomography (sLORETA). TBI patients displayed significant EEG slowing compared to controls with no significant differences between PTE and nonepileptic patients. BBB disruption was found in 82.4% of PTE compared to 25% of non-epileptic patients (P = .001) and could be observed even years following the trauma. The volume of cerebral cortex with BBB disruption was significantly larger in PTE patients (P = .001). Slow wave EEG activity was localized to the same region of BBB disruption in 70% of patients and correlated to the volume of BBB disrupted cortex. We finally present a patient suffering from early cortical dysfunction and BBB breakdown with a gradual and parallel resolution of both pathologies. Our findings demonstrate that BBB pathology is frequently found following mild TBI. Lasting BBB breakdown is found with increased frequency and extent in PTE patients. Based on recent animal studies and the colocalization found between the region of disrupted BBB and abnormal EEG activity, we suggest a role for a vascular lesion in the pathogenesis of PTE.

Blood–brain barrier disruption in post-traumatic epilepsy

Background:Traumatic brain injury (TBI) is an important cause of focal epilepsy. Animal experiments indicate that disruption of the blood–brain barrier (BBB) plays a critical role in the pathogenesis of post-traumatic...

Prevention of post-traumatic epilepsy by scavengers of reactive oxygen species which involved in the pathogenesis of post-traumatic epilepsy

Prevention of post-traumatic epilepsy by scavengers of reactive oxygen species which involved in the pathogenesis of post-traumatic epilepsy

脳代謝研究施設機能生化学部門最近の研究概説(I) -外傷性てんかんの成因に関する研究-

Post-traumatic epilepsy is characterized by epileptic seizures due to brain damage secondary to head injury, and it has been known since the days of Hippocrates. However, the pathogenesis of post-traumatic epilepsy in still unclear. Willmore et al (1978) first observed that injection of iron salts into the rat cortex induced a chronic epileptic focus (an experimental model of post-traumatic epilepsy). Head injury or hemorrhagic cortical infarction results in extravasation of blood and breakdown of red blood cells and hemoglobin. Biological iron is normally protein bound in hemoglobin and transferrin. Iron liberated from hemoglobin is thought to be associated with generation of active oxygen species. Moreover, hemoglobin itself may promote oxygen free radical generation. Oxygen free radicals, especially·OH is responsible for the induction of peroxidation of neuronal lipids, which causes damage to the neuronal membranes. On the other hand, ·OH accelerated the production of guanidino compounds in the brain, such as methylguanidine and guanidinoacetic acid. They are endogenous convulsants in the brain. These reactions may follow by excitatory and inhibitory neurotransmitter disorders, and may lead to development of epileptic discharges in the epileptogenic focus. Treatment with antioxidants such as epigallocatechin or a phosphate diester of vitamin E and C (EPC-K1), which are potent ·OH scavengers, may be useful for preventing development of the iron-induced epileptic focus.