Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice.

Xingjie Ping,Xiaoming Jin

doi:10.1371/journal.pone.0158231

Abstract

Posttraumatic epilepsy (PTE) usually develops in a small percentage of patients of traumatic brain injury after a varying latent period. Modeling this chronic neurological condition in rodents is time consuming and inefficient, which constitutes a significant obstacle in studying its mechanism and discovering novel therapeutics for its prevention and treatment. Partially isolated neocortex, or undercut, is known to induce cortical hyperexcitability and epileptiform activity in vitro, and has been used extensively for studying the neurophysiological mechanism of posttraumatic epileptogenesis. However, whether the undercut lesion in rodents causes chronic epileptic seizures has not been systematically characterized. Here we used a miniature telemetry system to continuously monitor electroencephalography (EEG) in adult C57BL mice for up to 3 months after undercut surgery. We found that 50% of animals developed spontaneous seizures between 16–50 days after injury. The mean seizure duration was 8.9±3.6 seconds, and the average seizure frequency was 0.17±0.17 times per day. There was no progression in seizure frequency and duration over the recording period. Video monitoring revealed behavioral arrests and clonic limb movement during seizure attacks. A pentylenetetrazol (PTZ) test further showed increased seizure susceptibility in the undercut mice. We conclude that undercut lesion in mice is a model of chronic PTE that involves spontaneous epileptic seizures.

Highlights

Of the 1.7 million victims of traumatic brain injury (TBI) in the United States annually, 5–53% of them, depending on the type and severity of brain injury, will develop chronic epileptic seizures [1, 2]
Posttraumatic epilepsy (PTE) has been observed and characterized in several animal models of TBI, such as lateral fluid percussion, controlled cortical impact, and weight drop injury[7,8,9,10,11]. These models are useful for studying the mechanisms of posttraumatic epileptogenesis [12]
Nissl staining of brain tissue at the end of EEG recording confirmed that the undercut lesions in all mice were neat and within layer VI and whiter matter border

Summary

Introduction

Of the 1.7 million victims of traumatic brain injury (TBI) in the United States annually, 5–53% of them, depending on the type and severity of brain injury, will develop chronic epileptic seizures [1, 2]. Posttraumatic epilepsy (PTE) accounts for 20% of symptomatic epilepsy in the general population It is poorly controlled by currently available antiepileptic drugs[1, 3], and constitutes one of the major conditions that compromise functional outcome and quality-oflife in TBI patients[4, 5][6]. PTE has been observed and characterized in several animal models of TBI, such as lateral fluid percussion, controlled cortical impact, and weight drop injury[7,8,9,10,11]. These models are useful for studying the mechanisms of posttraumatic epileptogenesis [12]. The low incidences of spontaneous seizures and the requirement for long periods of video/EEG monitoring in these models makes it very inefficient to use them for PLOS ONE | DOI:10.1371/journal.pone.0158231 June 27, 2016

Methods

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Conclusion