Diffuse traumatic brain injury results in concomitant re ...

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1University of Arizona College of Medicine-Phoenix, 2Barrow Neurological Institute ... Concomitant increases of TSPs and α2δ-1 with synaptic markers support a ...
Diffuse traumatic brain injury results in concomitant re-expression of thrombospondin 1&2 and increased synaptic markers in the hippocampus. SB Ogle1,2,3 , LM Law1,2,, SB Johnson1,3, PD Adelson1,2, J Lifshitz1,2,4, T Currier Thomas1,2,4 University of Arizona College of Medicine-Phoenix, 2Barrow Neurological Institute at Phoenix Children’s Hospital, 3Banner - University Medical Center, 4Phoenix VA Healthcare System

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Damaged circuits after traumatic brain injury (TBI) are repaired by the formation of new synaptic connections (synaptogenesis). For some TBI survivors, aberrant synaptogenesis misguides reparative processes leading to the development of persistent post-concussive symptoms. Synaptogenic regulation post-injury is unknown, and if misguided in the hippocampus (HC) could contribute to persistent emotional and cognitive impairment. Developmental synaptogenesis involves thrombospondin (TSP) interactions with the α2δ-1 subunit on voltage-gated calcium channels (α2δ-1), however, TSP is down-regulated in the adult CNS. In models of epilepsy and stroke, TSP re-expression regulates post-insult synaptogenesis, such that TSP-α2δ-1 antagonism modulates post-insult symptomatology. Hypothesis: TBI-induced reexpression of TSPs will concomitantly occur with increases in synaptic markers in the HC. Methods: Adult male Sprague-Dawley rats underwent sham or midline fluid percussion injury. At multiple time points post-injury, hippocampal biopsies of sham and injured animals were assessed for protein levels of TSPs, α2δ-1, and synaptic markers, GAP43 and PICK-1 using automated capillary western blot analysis. Statistical analyses used one-way ANOVA with a Fischer’s LSD post-hoc analysis. Results: TSP 1&2 and α2δ-1 protein levels significantly increased at 3 days post-injury (DPI) in comparison to sham (p=0.017; p=0.048; p=0.025; respectively). The synaptic markers, GAP43 and PICK-1, also significantly increased at 3 and 5 DPI in comparison to sham (p