TBI Rehabilomics Research: Conceptualizing a humoral triad for designing effective rehabilitation interventions

Abstract

Most areas of medicine use biomarkers in some capacity to aid in understanding how personal biology informs clinical care. This article draws upon the Rehabilomics research model as a translational framework for programs of precision rehabilitation and intervention research focused on linking personal biology to treatment response using biopsychosocial constructs that broadly represent function and that can be applied to many clinical populations with disability. The summary applies the Rehabilomics research framework to the population with traumatic brain injury (TBI) and emphasizes a broad vision for biomarker inclusion, beyond typical brain-derived biomarkers, to capture and/or reflect important neurological and non-neurological pathology associated with TBI as a chronic condition. Humoral signaling molecules are explored as important signaling and regulatory drivers of these chronic conditions and their impact on function. Importantly, secondary injury cascades involved in the humoral triad are influenced by the systemic response to TBI and the development of non-neurological organ dysfunction (NNOD). Biomarkers have been successfully leveraged in other medical fields to inform pre-randomization patient selection for clinical trials, however, this practice largely has not been utilized in TBI research. As such, the applicability of the Rehabilomics research model to contemporary clinical trials and comparative effectiveness research designs for neurological and rehabilitation populations is emphasized. Potential points of intervention to modify inflammation, hormonal, or neurotrophic support through rehabilitation interventions are discussed.

Challenges of Prevention for a Sustainable Personalized Medicine

“…Because rehabilitation requires an intimate understanding of how severe brain injuries impact disability, impairments, and QoL, PM represents a great opportunity for brain injury survivors to improve recovery [43]. In the perspective, we can consider the impact of omic sciences to address the most appropriate rehabilitation treatment on the basis of patients' needs, characteristics and life experience [30,[44][45][46].…”

Toward a Global and Reproducible Science for Brain Imaging in Neurotrauma: The ENIGMA Adult Moderate/Severe Traumatic Brain Injury Working Group

“…However, there is evidence for broader links between TBI and neurodegeneration, including microinfarcts, synucleinopathies and Parkinson's disease (Crane et al, 2016;Dams-O'Connor et al, 2016). Multiple mechanisms have been suggested to explain how TBI may be linked to neurodegeneration, including impaired immune function/inflammation (Jassam, Izzy, Whalen, McGavern, & El Khoury, 2017;Wagner & Kumar, 2019) increased vascular risk which has strong links to neurodegeneration (Sweeney et al, 2018;Zlokovic, 2011) and alterations in large-scale neural networks leading to disconnection (Hillary & Grafman, 2017;Jones et al, 2016). In vivo neuroimaging tools can contribute substantially to the understanding of mechanistic links between TBI and neurodegeneration.…”

Secreted Peptides for Diagnostic Trajectory Assessments in Brain Injury Rehabilitation

“…6 Although this toolkit is highly impactful, 7 the addition of pathobiology-based biomarker feedback on patient recovery would be advantageous in optimizing interventions and prognostication. 8 Indeed, optimizing individualized dose, intensity, and timing of therapy remains one of the greatest challenges for practitioners that could benefit from effective TBI rehabilitation molecular diagnostics. 9,10…”

“…11-13 The multivariate, quantifiable output promises a greater degree of pathophysiological-relevant information than presently attained via clinical variables alone, which in combination, would provide more robust, individualized data for injury assessment, monitoring interventions, and prognosticating outcomes within a rehabilomics research model. 8 Yet the application of omic mass spectrometry to TBI diagnostics has largely been limited to studying the acute-phase response. 12,14 TBI pathophysiology underlying secondary sequelae continues to evolve in the postacute period, 8 warranting discrete biomarker assays to inform on patient progress during rehabilitation and portend future recovery.…”

“…8 Yet the application of omic mass spectrometry to TBI diagnostics has largely been limited to studying the acute-phase response. 12,14 TBI pathophysiology underlying secondary sequelae continues to evolve in the postacute period, 8 warranting discrete biomarker assays to inform on patient progress during rehabilitation and portend future recovery. 11…”