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.

Keywords: Astrocytes; Chemokines; Cytokines; Epileptogenesis; Inflammation; Microglia; TBI; Traumatic brain injury.

Fig. 1

Microglia (purple, left), astrocytes (pink, bottom), and neurons (red, upper right) are activated and altered after TBI. Cytokines interleukin-1α, TNF, and complement component 1 subcomponent q (C1q) are secreted by activated microglia and can induce the A1 astrocyte phenotype. Astrocytes suffer gap junction uncoupling and have impaired neurotransmitter (NT) clearance and metabolic recycling from synapses. Cytokines interleukin-6, interleukin-1β, transforming growth factor beta (TGFβ), and chemokine CCL2 are secreted in high concentrations creating a neuroinflammatory milieu. Cells adapted from Blausen Medical Gallery [58]