Biomarkers associated with functional improvement after stroke rehabilitation: a systematic review and meta-analysis of randomized controlled trials

OBJECTIVE: This study aims to identify blood and cerebrospinal fluid biomarkers that are correlated to the functional improvement of stroke patients after rehabilitation therapy, and provide ideas for the treatment and evaluation of stroke patients. METHODS: The PubMed, Web of Science, and Embase databases were searched for articles published in the English language, from inception to December 8, 2022. RESULTS: A total of 9,810 independent records generated 50 high-quality randomized controlled trials on 119 biomarkers. Among these records, 37 articles were included for the meta-analysis (with a total of 2,567 stroke patients), and 101 peripheral blood and cerebrospinal fluid biomarkers were included for the qualitative analysis. The quantitative analysis results revealed a moderate quality evidence that stroke rehabilitation significantly increased the level of brain-derived neurotrophic factor (BDNF) in serum. Furthermore, the low-quality evidence revealed that stroke rehabilitation significantly increased the concentration of serum noradrenaline (NE), peripheral blood superoxide dismutase (SOD), peripheral blood albumin (ALB), peripheral blood hemoglobin (HB), and peripheral blood catalase (CAT), but significantly decreased the concentration of serum endothelin (ET) and glutamate. In addition, the changes in concentration of these biomarkers were associated with significant improvements in post-stroke function. The serum BNDF suggests that this can be used as a biomarker for non-invasive brain stimulation (NIBS) therapy, and to predict the improvement of stroke patients. CONCLUSION: The concentration of serum BNDF, NE, ET and glutamate, and peripheral blood SOD, ALB, HB and CAT may suggest the function improvement of stroke patients.