Secreted Peptides for Diagnostic Trajectory Assessments in Brain Injury Rehabilitation

Abstract

Background Rehabilitation following traumatic brain injury (TBI) significantly improves outcomes; yet TBI heterogeneity raises the need for molecular evidence of brain recovery processes to better track patient progress, evaluate therapeutic efficacy, and provide prognostication. Objective Here, we assessed whether the trajectory of TBI-responsive peptides secreted into urine can produce a predictive model of functional recovery during TBI rehabilitation. Methods The multivariate urinary peptidome of 12 individuals with TBI was examined using quantitative peptidomics. Measures were assessed upon admission and discharge from inpatient rehabilitation. A combination of Pavlidis template matching and partial least-squares discriminant analysis was used to build models on Disability Rating Scale (DRS) and Functional Independence Measure (FIM) scores, with participants bifurcated into more or less functional improvement groups. Results The produced models exhibited high sensitivity and specificity with the area under the receiver operator curve being 0.99 for DRS- and 0.95 for FIM-based models using the top 20 discriminant peptides. Predictive ability for each model was assessed using robust leave-one-out cross-validation with Q2 statistics of 0.64 ( P = .00012) and 0.62 ( P = .011) for DRS- and FIM-based models, respectively, both with a high predictive accuracy of 0.875. Identified peptides that discriminated improved functional recovery reflected heightened neuroplasticity and synaptic refinement and diminished cell death and neuroinflammation, consistent with postacute TBI pathobiology. Conclusions Produced models of urine-based peptide measures reflective of ongoing recovery pathobiology can inform on rehabilitation progress after TBI, warranting further study to assess refined stratification across a larger population and efficacy in assessing therapeutic interventions.