Neuropathophysiological Mechanisms and Treatment Strategies for Post-traumatic Epilepsy

Abstract

Traumatic brain injury (TBI) is a leading cause of death in young adults and a risk factor for acquired epilepsy. Severe TBI, after a period of time, causes numerous neuropsychiatric and neurodegenerative problems with varying comorbidities; and brain homeostasis may never be restored. As a consequence of disrupted equilibrium, neuropathological changes such as circuit remodeling, reorganization of neural networks, changes in structural and functional plasticity, predisposition to synchronized activity, and post-translational modification of synaptic proteins may begin to dominate the brain. These pathological changes, over the course of time, contribute to conditions like Alzheimer disease, dementia, anxiety disorders, and post-traumatic epilepsy (PTE). PTE is one of the most common, devastating complications of TBI; and of those affected by a severe TBI, more than 50% develop PTE. The etiopathology and mechanisms of PTE are either unknown or poorly understood, which makes treatment challenging. Although anti-epileptic drugs (AEDs) are used as preventive strategies to manage TBI, control acute seizures and prevent development of PTE, their efficacy in PTE remains controversial. In this review, we discuss novel mechanisms and risk factors underlying PTE. We also discuss dysfunctions of neurovascular unit, cell-specific neuroinflammatory mediators and immune response factors that are vital for epileptogenesis after TBI. Finally, we describe current and novel treatments and management strategies for preventing PTE.

Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways

“…PTZ can activate microglia and induce the release of TNF-α, IL-1β, and IL-6 ( Kandeda et al, 2022d ). These cytokines can increase glutamate level and stimulate endocytosis of GABA receptors ( Temp et al, 2017 ; Sharma et al, 2021 ). Administration of the aqueous extract significantly reduced the levels of these pro-inflammatory cytokines, suggesting anti-inflammatory activity.…”

Posttraumatic epilepsy: clinical, diagnostic and therapeutic features

“…около 35% ЧМТ возникают в результате падений, 17% -в результате дорожно-транспортных происшествий и 10% -в результате нападений, в то время как в 21% случаев причина не регистрируется [2]. Являясь неоднородной патологией с разнообразными клиническими проявлениями, ЧМТ отличается от других острых страданий нервной системы (например, ишемического или геморрагического инсульта) тем, что неврологический дефицит, инициируемый травмой, может проявиться через несколько дней, месяцев или даже лет после причинных событий [3].…”

Spike Timing-Dependent Plasticity with Enhanced Long-Term Depression Leads to an Increase of Statistical Complexity

“…Neurodegenerative diseases are disorders that may or may not trigger an increase in cell death, but all involve a loss of function and/or neural structures [ 8 ]. Neural damage usually has various origins, among them, one of the most important is damage to the neuronal membrane, which is responsible for propagating the action potential or spike.…”