The pathophysiology of repetitive concussive XXXX in experimental models; new developments and open questions.

@entity1545 @entity1 @entity131 @entity308 @entity16 @entity409 @entity3756 @entity21 @entity130
In recent years, there has been an increasing interest in the pathophysiology of repetitive concussive @entity131 (rcTBI) in large part due to the association with dramatic cases of progressive @entity16 in professional athletes, military personnel, and others. However, our understanding of the pathophysiology of rcTBI is less advanced than for more severe @entity1545 . Most prominently, the mechanisms underlying traumatic @entity21 , microglial activation, @entity409 , and progressive tau pathology are not yet known. In addition, the role of injury to dendritic spine cytoskeletal structures, vascular reactivity impairments, and microthrombi are intriguing and subjects of ongoing inquiry. Methods for quantitative analysis of @entity21 , @entity130 , and synaptic loss need to be refined for the field to move forward in a rigorous fashion. We and others are attempting to develop translational approaches to assess these specific pathophysiological events in both animals and @entity1 to facilitate clinically relevant pharmacodynamic assessments of candidate therapeutics. In this article, we review and discuss several of the recent experimental results from our lab and others. We include new initial data describing the difficulty in modeling progressive tau pathology in experimental rcTBI, and results demonstrating that @entity3756 can alleviate social interaction deficits and @entity308 -like behaviors following experimental rcTBI plus foot shock stress. Furthermore, we propose a discrete set of open, experimentally tractable questions that may serve as a framework for future investigations. In addition, we also raise several important questions that are less experimentally tractable at this time, in hopes that they may stimulate future methodological developments to address them. This article is part of a Special Issue entitled " @entity131 ".
