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

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Abstract

Objective

To identify postinjury physiologic, behavioral, and cognitive biomarkers for posttraumatic epilepsy to enrich study populations for long‐term antiepileptogenesis studies.

Methods

The EPITARGET cohort with behavioral follow‐up and 1‐month 24/7 video‐electroencephalography (vEEG) monitoring included 115 adult male Sprague‐Dawley rats with lateral fluid‐percussion–induced traumatic brain injury (TBI), 23 sham‐operated controls, and 13 naive rats. Animals underwent assessment of somatomotor performance (composite neuroscore), anxiety‐like behavior (elevated plus maze, open field), spatial memory (Morris water maze), and depression‐like behavior (Porsolt forced swim, sucrose preference). Impact force, postimpact apnea time, postimpact seizure‐like behavior, and body weight were monitored.

Results

TBI rats were impaired in the composite neuroscore (P  < .001) on days (D) 2‐14 and in the spatial memory test (P  < .001) on D35‐39 post‐TBI. Differences in the elevated plus‐maze (D28 and D126) and in the open field (D29 and D127) between TBI rats and controls were meager. No differences were observed in the Porsolt forced swim and sucrose preference tests as compared with sham‐operated controls. Epilepsy developed in 27% of rats by the end of the sixth month. None of the behavioral or cognitive outcome measures discriminated rats with or without epilepsy. The receiver‐operating characteristic analysis indicated that a decrease in body weight between D0 and D4 differentiated TBI rats with epilepsy from TBI rats without epilepsy (48% sensitivity, 83% specificity, area under the curve [AUC] 0.679, confidence interval [CI] 95% 0.56‐0.80, P  < .01). A 16% body weight decrease during D0‐D4 could be used as a biomarker to enrich the study population from 27% (observed) to 50%.

Significance

Single behavioral and cognitive outcome measures showed no power as prognostic/diagnostic biomarkers for posttraumatic epilepsy. A reduction in body weight during the first postinjury week showed some prognostic value for posttraumatic epileptogenesis and could serve as a subacute measure for selectively enriching the study population for long‐term preclinical biomarker and therapy discovery studies of posttraumatic epileptogenesis.

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