A Rehabilomics focused perspective on molecular mechanisms underlying neurological injury, complications, and recovery after severe TBI

Abstract

The molecular mechanisms underlying TBI pathophysiology and recovery are both complex and varied. Further, the pathology underlying many of the clinical sequelae observed in this population evolve over the acute injury period and encompass the subacute and chronic phases of recovery, supporting the contemporary concept that TBI is a chronic disease rather than a static insult from which limited recovery occurs. TBI related complications can also span from acute care to the very chronic stages of recovery that occur years after the initial trauma. Despite ongoing neurodegeneration, the TBI recovery period is also characterized by a propensity for neuroplasticity and rewiring through multiple mechanisms. This review summarizes key elements of acute pathophysiology, how they link to structural damage and ongoing degeneration, and how this process coincides with a permissive neuroplastic environment. The pathophysiology of selected TBI related complications is also discussed. Each of these concepts is studied through the lens of Rehabilomics, wherein an emphasis is placed on biomarker studies characterizing these pathophysiological mechanisms, and biomarker profiles are assessed in relation to multi-modal outcomes and susceptibility to rehabilitation relevant complications. In reviewing these concepts, implications for future research and theranostic principles for patient care are presented.