How recurrent traumatic brain injury (rTBI) alters brain function years after insult is largely unknown. This study aims to characterize the mechanistic cause for long-term brain deterioration following rTBI using a rat model.
Eighteen Sprague-Dawley wild-type rats underwent bilateral rTBI using a direct skull impact device or sham treatment, once per week for five weeks, and were euthanized 56 weeks after the first injury. Weekly rotorod performance measured motor deficits. Beam walk and grip strength were also assessed. Brain tissue were stained and volume was computed using Stereo Investigator’s Cavalieri Estimator. The L5 cortical layer proximal to the injury site was microdissected and submitted for sequencing with count analyzed using R “DESeq2” and “GOStats”. Brain-derived neurotrophic factor (BDNF) levels were determined using enzyme-linked immunosorbent assay.
Rotorod data demonstrated permanent deficits one year after rTBI. Decreased beam walk performance and grip strength was noted among rTBI rodents. rTBI led to thinner cortex and thinner corpus callosum, enlarged ventricles, and differential expression of 72 genes (25 upregulated, 47 downregulated) including dysregulation of those associated with TBI (BDNF, NR4A1/2/3, Arc, and Egr) and downregulation in pathways associated with neuroprotection and neuroplasticity. Over the course of the study BDNF levels decreased in both rTBI and sham rodents, and at each time point the decrease in BDNF was more pronounced after rTBI.
rTBI causes significant long-term alteration in brain health leading to permanent motor deficits, cortical and corpus callosum thinning, and expansion of the lateral ventricles. Gene expression and BDNF analysis suggest a significant drop in pathways associated with neuroplasticity and neuroprotection. Although rTBI may not cause immediate neurological abnormalities, continued brain deterioration occurs after the initial trauma in part due to a decline in genes associated with neuroplasticity and neuroprotection.
Level of Evidence
N/A – basic science manuscript