Acute non-convulsive status epilepticus after experimental traumatic brain injury in rats

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 sham-operated experimental control or lateral FPI-induced severe TBI groups. Electrodes were implanted right after impact or sham-operation, then video-electroencephalogram (EGG) monitoring was started. In addition, video-EEG was recorded from naïve rats. During the first 48 h post-TBI, injured rats had seizures which were intermingled with other epileptiform EEG patterns typical to non-convulsive 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 s. Analysis of high-resolution videos indicated that only 41% of electrographic seizures associated with behavioral abnormalities were typically subtle (Racine scale 1-2). Fifty-nine % 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 shows 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.