Epileptogenesis following experimentally induced traumatic brain injury – a systematic review

Abstract

<jats:title>Abstract</jats:title><jats:p>Traumatic brain injury (TBI) is a complex neurotrauma in civilian life and the battlefield with a broad spectrum of symptoms, long-term neuropsychological disability, as well as mortality worldwide. Posttraumatic epilepsy (PTE) is a common outcome of TBI with unknown mechanisms, followed by posttraumatic epileptogenesis. There are numerous rodent models of TBI available with varying pathomechanisms of head injury similar to human TBI, but there is no evidence for an adequate TBI model that can properly mimic all aspects of clinical TBI and the first successive spontaneous focal seizures follow a single episode of neurotrauma with respect to epileptogenesis. This review aims to provide current information regarding the various experimental animal models of TBI relevant to clinical TBI. Mossy fiber sprouting, loss of dentate hilar neurons along with recurrent seizures, and epileptic discharge similar to human PTE have been studied in fluid percussion injury, weight-drop injury, and cortical impact models, but further refinement of animal models and functional test is warranted to better understand the underlying pathophysiology of posttraumatic epileptogenesis. A multifaceted research approach in TBI model may lead to exploration of the potential treatment measures, which are a major challenge to the research community and drug developers. With respect to clinical setting, proper patient data collection, improved clinical trials with advancement in drug delivery strategies, blood-brain barrier permeability, and proper monitoring of level and effects of target drug are also important.</jats:p>

Activated N‐methyl‐D‐aspartate receptor ion channels detected in focal epilepsy with [18F]GE‐179 positron emission tomography

“…CBZ, carbamazepine; CLB, clobazam; CLZ, clonazepam; GBT, gabapentin; LAC, lacosamide; OXC, oxcarbazepine; VPA, valproate; ZNS, zonisamide in subjects with suspected focal epilepsy. [ 18 F]GE-179 PET may have future clinical utility in supporting a diagnosis of epilepsy or for helping to identify subjects at a higher risk of developing epilepsy after brain insults such as stroke [43][44][45][46][47] and traumatic brain injury, 44,48,49 where increased excitotoxicity and elevated NMDAR levels are known to play a role.…”

Diversity of kindling of limbic seizures after lateral fluid percussion injury in the rat

“…Lateral fluid percussion injury (LFPI) in rats is employed to model post-traumatic epilepsy (PTE). 1,2 Documenting PTE has been mainly relying on video and EEG. [3][4][5] A notable weakness of such approach is its binary nature: It assumes that LFPI is either epileptogenic or is largely inconsequential.…”

“…Lateral fluid percussion injury (LFPI) in rats is employed to model post‐traumatic epilepsy (PTE) 1,2 . Documenting PTE has been mainly relying on video and EEG 3–5 .…”

Role of Astrocytes in Post-traumatic Epilepsy

“…Different from other types of epilepsy, post-traumatic epilepsy with a more complicated etiology is induced by many pathobiological mechanisms in parallel. In order to clarify the extent and exact mechanisms of the astrocyte involved, various kinds of post-traumatic epilepsy-induced traumatic brain injury models have been tested, including controlled cortical impact and the fluid percussion injury models (20), impact-acceleration models (21), weight-drop models, ferric chloride models, and so on (22). Some researchers demonstrated that the loss of astrocyte homeostatic functions possibly contributes to post-traumatic epilepsy (21).…”