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.
Highlights
More than 3 million people in United States suffer a Traumatic brain injury (TBI) each year
Four key elements—excitotoxicity, neuroinflammation, oxidative stress, and neurodegeneration—are the primary pathognomonic mechanisms responsible for post-traumatic epilepsy (PTE); and it is well known that TBI initiate cycles of neuroinflammatory events that elicit the oxidative stress response tripping a series of events and cycles that exacerbate the acute stage and lead to chronic conditions (Figure 6)
The goal of this review is to understand the mechanisms of epileptogenesis after TBI and identify, develop, and validate therapeutic strategies to prevent PTE
Summary
More than 3 million people in United States suffer a TBI each year. Among these cases, 80% are mild, 10% moderate, and about 10% severe, accounting for ∼300,000 hospitalizations and ∼50,000 fatalities, annually (Maas et al, 2017). Many traumatic brain injuries cause long-term disabilities, cognitive decline, psychiatric illness, and post-traumatic disorders. About 35% of TBI result from falls, 17% from motor vehicle accidents, and 10% from assaults, while in 21% of the cases, the cause was not recorded (Ding et al, 2016; Centers for Disease Control and Prevention, 2019). Incidence rates are higher in both males and females up to 9 years of age, during teen years, and towards the end of life (>74 years of age). 2% of U.S population live with long-lasting disabilities
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