The Quest to Model XXXX : A Multiple Model and Injury Paradigm Experience.

@entity1 @entity131 @entity13859 @entity19 @entity73 @entity179 @entity35 @entity8638 @entity130
@entity179 following a history of neurotrauma is frequently associated with @entity73 . In order to enhance understanding about the underlying pathophysiology linking neurotrauma to @entity179 , a multi-model preclinical approach must be established to account for the different @entity130 and pathophysiologic mechanisms. We investigated the development of tau pathology and behavioral changes using a multi-model and multi-institutional approach, comparing the preclinical results to @entity13859 patterns seen in post-mortem @entity1 samples from athletes diagnosed with @entity8638 ( @entity8638 ). We utilized a scaled and validated blast-induced @entity131 model in @entity35 and a modified pneumatic closed-head impact model in @entity19 . Tau hyperphosphorylation was evaluated by western blot and immunohistochemistry. Elevated-plus maze and Morris water maze were employed to measure impulsive-like behavior and @entity73 respectively. Animals exposed to single blast (~50 PSI reflected peak overpressure) exhibited elevated AT8 immunoreactivity in the contralateral hippocampus at 1   month compared to controls (q   =   3.96, p   <   0.05). Animals exposed to repeat blast (six blasts over 2   weeks) had increased AT8 (q   =   8.12, p   <   0.001) and AT270 (q   =   4.03, p   <   0.05) in the contralateral hippocampus at 1   month @entity130 compared to controls. In the modified controlled closed-head impact @entity19 model, no significant difference in AT8 was seen at 7   days, however a significant elevation was detected at 1   month following injury in the ipsilateral hippocampus compared to control (q   =   4.34, p   <   0.05). Elevated-plus maze data revealed that @entity35 exposed to single blast (q   =   3.53, p   <   0.05) and repeat blast (q   =   4.21, p   <   0.05) spent more time in seconds exploring the open arms compared to controls. Morris water maze testing revealed a significant difference between groups in acquisition times on days 22-27. During the probe trial, single blast (t   =   6.44, p   <   0.05) and repeat blast (t   =   8.00, p   <   0.05) @entity35 spent less time in seconds exploring where the platform had been located compared to controls. This study provides a multi-model example of replicating tau and behavioral changes in animals and provides a foundation for future investigation of @entity8638 pathophysiology and therapeutic development.
