Neuroinflammatory mechanisms of post-traumatic epilepsy

Abstract

Background: Traumatic brain injury (TBI) occurs in as many as 64-74 million people worldwide each year and often results in one or more post-traumatic syndromes, including depression, cognitive, emotional, and behavioral deficits. TBI can also increase seizure susceptibility, as well as increase the incidence of epilepsy, a phenomenon known as post-traumatic epilepsy (PTE). Injury type and severity appear to partially predict PTE susceptibility. However, a complete mechanistic understanding of risk factors for PTE is incomplete. Main body: From the earliest days of modern neuroscience, to the present day, accumulating evidence supports a significant role for neuroinflammation in the post-traumatic epileptogenic progression. Notably, substantial evidence indicates a role for astrocytes, microglia, chemokines, and cytokines in PTE progression. Although each of these mechanistic components is discussed in separate sections, it is highly likely that it is the totality of cellular and neuroinflammatory interactions that ultimately contribute to the epileptogenic progression following TBI. Conclusion: This comprehensive review focuses on the neuroinflammatory milieu and explores putative mechanisms involved in the epileptogenic progression from TBI to increased seizure-susceptibility and the development of PTE.

Mechanisms of Drug Resistance in the Pathogenesis of Epilepsy: Role of Neuroinflammation. A Literature Review

“…The general prognosis of epilepsy is favorable for the majority of patients and 55-68% of them tend to achieve long-term remission [23], but in the case of generalized tonic-clonic seizures, nocturnal seizures and refractory or drug-resistant epilepsy, death is not uncommon [24]. The development of epilepsy can be associated with a wide variety of factors, including genetic predisposition, malformations, traumatic brain injuries that occur annually in 64-74 million people [25], chemical exposure, hypoxia or stroke. Many of these pathologies are associated with neuronal death.…”

“…Several researchers have shown that the concentration of IL-4, IL-8 and IL-17 can correlate with the frequency and severity of seizures, suggesting a key role for cytokines in the diagnosis and treatment of epilepsy [38,40]. Most chemokines and their receptors promote neuroinflammation by involving peripheral monocytes and promoting glial cell activation [25]. Table 1 provides examples of some mediators involved in neuroinflammation and epilepsy and their role in these processes.…”

“…In patients and animal models of epilepsy, increased expression levels of these cytokines in the brain are observed. They increase the excitability of neurons and thus are considered to be involved in epileptogenesis [25,41].…”

“…There is an increase of anti-inflammatory cytokines expression (Arg1, IL-4 and IL-10) by microglia in epilepsy [25]. IL-10 is usually characterized as an anti-inflammatory cytokine.…”

Antagonism of Macrophage Migration Inhibitory Factory (MIF) after Traumatic Brain Injury Ameliorates Astrocytosis and Peripheral Lymphocyte Activation and Expansion

“…In addition to cellular mediators, specific inflammatory cytokines and chemokines have been demonstrated to be pro-epileptogenic [ 17 ]. These include IL1β, IL6, TNFα, TGFβ, [ 6 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”