Neuroinflammation in Post-Traumatic Epilepsy: Pathophysiology and Tractable Therapeutic Targets.

Sharma, Rishabh; Leung, Wai Lam; Zamani, Akram; O'Brien, Terence J.; Casillas Espinosa, Pablo M.; Semple, Bridgette D.

Epilepsy is a common chronic consequence of traumatic brain injury (TBI), contributing to increased morbidity and mortality for survivors. As post-traumatic epilepsy (PTE) is drug-resistant in at least one-third of patients, there is a clear need for novel therapeutic strategies to prevent epilepsy from developing after TBI, or to mitigate its severity. It has long been recognized that seizure activity is associated with a local immune response, characterized by the activation of microglia and astrocytes and the release of a plethora of pro-inflammatory cytokines and chemokines. More recently, increasing evidence also supports a causal role for neuroinflammation in seizure induction and propagation, acting both directly and indirectly on neurons to promote regional hyperexcitability. In this narrative review, we focus on key aspects of the neuroinflammatory response that have been implicated in epilepsy, with a particular focus on PTE. The contributions of glial cells, blood-derived leukocytes, and the blood–brain barrier will be explored, as well as pro- and anti-inflammatory mediators. While the neuroinflammatory response to TBI appears to be largely pro-epileptogenic, further research is needed to clearly demonstrate causal relationships. This research has the potential to unveil new drug targets for PTE, and identify immune-based biomarkers for improved epilepsy prediction.

INFLAMMATION; EPILEPSY; BRAIN injuries; NEUROGLIA; PATHOLOGICAL physiology

Brain Sciences (2076-3425), 2019, Vol 9, Issue 11, p318

2076-3425

Academic Journal

10.3390/brainsci9110318