Secreted Peptides for Diagnostic Trajectory Assessments in Brain Injury Rehabilitation.

Autor:	Patel PD; Virginia Commonwealth University, School of Medicine, Richmond, VA, USA., Stafflinger JE; Virginia Commonwealth University, School of Medicine, Richmond, VA, USA., Marwitz JH; Virginia Commonwealth University, School of Medicine, Richmond, VA, USA., Niemeier JP; Virginia Commonwealth University, School of Medicine, Richmond, VA, USA., Ottens AK; Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
Jazyk:	angličtina
Zdroj:	Neurorehabilitation and neural repair [Neurorehabil Neural Repair] 2021 Feb; Vol. 35 (2), pp. 169-184. Date of Electronic Publication: 2020 Dec 17.
DOI:	10.1177/1545968320975428
Abstrakt:	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 Q 2 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.
Databáze:	MEDLINE
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