Acute non-convulsive status epilepticus after experimental traumatic brain injury in rats
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CitationAndrade, Pedro. Banuelos-Cabrera, Ivette. Lapinlampi, Niina. Paananen, Tomi. Ciszek, Robert. Ndode-Ekane, Xavier Ekolle. Pitkanen, Asla. (2019). Acute non-convulsive status epilepticus after experimental traumatic brain injury in rats. Journal of neurotrauma, [Epub ahead of print 25 Feb 2019], 10.1089/neu.2018.6107.
Severe traumatic brain injury (TBI) induces seizures or status epilepticus (SE) in 20–30% of patients during the acutephase. We hypothesized that severe TBI induced with lateral fluid-percussion injury (FPI) triggers post-impact SE. AdultSprague-Dawley male rats were anesthetized with isoflurane and randomized into the sham-operated experimental controlor lateral FPI-induced severe TBI groups. Electrodes were implanted right after impact or sham-operation, then video-electroencephalogram (EEG) monitoring was started. In addition, video-EEG was recorded from naı ̈ve rats. During thefirst 72 h post-TBI, injured rats had seizures that 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 sei-zures/rat). Mean latency from the impact to the first electrographic seizure was 18.4–15.1 h. Mean seizure duration was86–57 sec. Analysis of high-resolution videos indicated that only 41% of electrographic seizures associated with behavioralabnormalities, which were typically subtle (Racine scale 1–2). Fifty-nine percent of electrographic seizures did not show anybehavioral manifestations. In most of the rats, epileptiform EEG patterns began to decay spontaneously on Days 5–6 afterTBI. Interestingly, also a few sham-operated and naı ̈ve rats had post-operation seizures, which were not associated with EEGbackground patterns typical to non-convulsive SE seen in TBI rats. To summarize, our data show that lateral FPI-inducedTBI results in non-convulsive SE with subtle behavioral manifestations; this explains why it has remained undiagnosed untilnow. The lateral FPI model provides a novel platform for assessing the mechanisms of acute symptomatic non-convulsive SEand for testing treatments to prevent post-injury SE in a clinically relevant context.