Acute Non-Convulsive Status Epilepticus after Experimental Traumatic Brain Injury in Rats

Abstract

Severe traumatic brain injury (TBI) induces seizures or status epilepticus (SE) in 20-30% of patients during the acute phase. We hypothesized that severe TBI induced with lateral fluid-percussion injury (FPI) triggers post-impact SE. Adult Sprague-Dawley male rats were anesthetized with isoflurane and randomized into the sham-operated experimental control or lateral FPI-induced severe TBI groups. Electrodes were implanted right after impact or sham-operation, then videoelectroencephalogram (EEG) monitoring was started. In addition, video-EEG was recorded from naïve rats. During the first 72 h post-TBI, injured rats had seizures that were intermingled with other epileptiform EEG patterns typical to nonconvulsive SE, including occipital intermittent rhythmic delta activity, lateralized or generalized periodic discharges, spike-and-wave complexes, poly-spikes, poly-spike-and-wave complexes, generalized continuous spiking, burst suppression, or suppression. Almost all (98%) of the electrographic seizures were recorded during 0-72 h post-TBI (23.2-17.4 seizures/rat). Mean latency from the impact to the first electrographic seizure was 18.4-15.1 h. Mean seizure duration was 86-57 sec. Analysis of high-resolution videos indicated that only 41% of electrographic seizures associated with behavioral abnormalities, which were typically subtle (Racine scale 1-2). Fifty-nine percent of electrographic seizures did not show any behavioral manifestations. In most of the rats, epileptiform EEG patterns began to decay spontaneously on Days 5-6 after TBI. Interestingly, also a few sham-operated and naïve rats had post-operation seizures, which were not associated with EEG background patterns typical to non-convulsive SE seen in TBI rats. To summarize, our data show that lateral FPI-induced TBI results in non-convulsive SE with subtle behavioral manifestations; this explains why it has remained undiagnosed until now. The lateral FPI model provides a novel platform for assessing the mechanisms of acute symptomatic non-convulsive SE and for testing treatments to prevent post-injury SE in a clinically relevant context.

Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid‐percussion injury in rats

“…It is well known that animals with lateral FPI lose weight, which apparently relates to brain injury-induced loss of consciousness and motor impairment, but also to nonconvulsive status epilepticus, which can last for 3-4 days. 34 Thereafter, the body weight begins to increase, eventually reaching the level of age-matched sham-operated experimental controls and naive animals. Unexpectedly, we found that the weight loss was more pronounced and the weight gain slower in TBI+ rats than in TBI− rats.…”

“…We recently demonstrated that almost all animals with lateral FPI develop postinjury nonconvulsive status epilepticus, which is associated with both immediate (<24 hours) electrographic seizures, typically occurring within a few hours after impact, and early (<7 days) electrographic seizures, most of which are nonconvulsive and occur during D1-D4 after TBI. 34 Whether the "immediate post-impact seizure-like behavior" associates with electrographic characteristics of a seizure, thus belonging to the category of "immediate seizures," remains to be determined, however, despite the technical challenges related to EEG recordings immediately after the impact. Our findings revealed no association between acute seizure-like behavior and development of PTE, consistent with our previous study.…”

Neocortical injury–induced status epilepticus

“…16 Previous studies reported that severe traumatic brain injury induced by lateral fluid-percussion injury to rats caused seizures and SE. 17,18 Co implanted in the motor cortex caused focal seizures. [19][20][21] Co binds to oxygen-binding molecules and causes functional hypoxia, triggers neuronal death, and increases expression of vascular endothelial growth factor.…”

In Vitro and In Vivo Pipeline for Validation of Disease-Modifying Effects of Systems Biology-Derived Network Treatments for Traumatic Brain Injury—Lessons Learned

“…The poor performance could relate to dizziness and sedation, which are well-known side effects of clomipramine in humans [61]. Recently, we found that rats with lateral FPI have non-convulsive status epilepticus lasting approximately 3 days [65]. Thus, some of our animals could still have had epileptiform activity when the clomipramine treatment was initiated.…”