Identifying new blood biomarkers of neuroplasticity associated with rehabilitation outcomes after stroke

Abstract

Biomarker; Neuroplasticity; Recovery

Biomarcador; Neuroplasticitat; Recuperació

Biomarcador; Neuroplasticidad; Recuperación

Blood biomarkers in stroke patients seek to guide decision-making in clinical practice, but research on those that respond to brain recovery and their relationship with rehabilitation is still limited. Our aim was to explore the value of known neuroplasticity-related molecules, such as endostatin, growth and differentiation factor-10 (GDF-10), urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR), as blood biomarkers of recovery during poststroke rehabilitation. In an observational, prospective and multicenter study, biomarker levels were assessed after stroke in a cohort of 62 stroke patients with outcome evaluations and blood sampling before starting rehabilitation and during therapy at 1, 3 and 6 months of first visit, and in 43 control subjects. Serum levels were determined by Enzyme-Linked Immunosorbent Assay (ELISA) together with a complete battery of sensorimotor and functional tests/scales: modified Rankin Scale (mRS), Barthel Index (BI), Fugl-Meyer Assessment (FMA) for the upper extremity, Functional Ambulation Categories (FAC), Chedoke Arm and Hand Activity Inventory (CAHAI), 10-m walk test and the Medical Research Council (MRC). Statistical mixed linear models were built to investigate its prognostic value. The results revealed that, compared to controls, only endostatin was significantly increased at baseline after stroke (p < 0.01). Interestingly, the highest baseline GDF-10 or uPAR values were related to unfavorable scores during the complete follow-up (p < 0.05 for walking speed or MRC with GDF-10, and for FMA or MRC with uPAR), whereas decreased endostatin or increased GDF-10 biomarker changes at first month of rehabilitation were related to greater sensorimotor and functional improvements during follow-up (p < 0.05 for FMA or MRC with endostatin, and CAHAI or BI with GDF-10). Our results position endostatin, GDF-10 and uPAR as potential blood biomarkers to monitor recovery during rehabilitation after stroke.

N.G-R. is doing a doctorate at the Departament de Medicina de la Universitat Autònoma de Barcelona. Research grants from the Instituto de Salud Carlos III with European Regional Development or Next Generation Founds to A.R. or J.B.S. supported this study (PI16/00981, PI19/00186, RD16/0019/0021, RD16/0019/0008, RD21/0006/0007, and RD21/0006/0014), as well as the 2021-SGR-0656 programme from the Generalitat de Catalunya-AGAUR. N.G-R. received a predoctoral fellowship from VHIR, and MG-G. received a research support grant (PERIS, SLT017/20/000197).