Protein biomarkers of epileptogenicity after traumatic brain injury

Traumatic brain injury (TBI) is a major risk factor for acquired epilepsy. Post-traumatic epilepsy (PTE) develops over time in up to 50% of patients with severe TBI. PTE is mostly unresponsive to traditional anti-seizure treatments suggesting distinct, injury-induced pathomechanisms in the development of this condition. Moderate and severe TBIs cause significant tissue damage, bleeding, neuron and glia death, as well as axonal, vascular, and metabolic abnormalities. These changes trigger a complex biological response aimed at curtailing the physical damage and restoring homeostasis and functionality. Although a positive correlation exists between the type and severity of TBI and PTE, there is only an incomplete understanding of the time-dependent sequelae of TBI pathobiologies and their role in epileptogenesis. Determining the temporal profile of protein biomarkers in the blood (serum or plasma) and cerebrospinal fluid (CSF) can help to identify pathobiologies underlying the development of PTE, high-risk individuals, and disease modifying therapies. Here we review the pathobiological sequelae of TBI in the context of blood- and CSF-based protein biomarkers, their potential role in epileptogenesis, and discuss future directions aimed at improving the diagnosis and treatment of PTE.