Reporting of pre-analytical variables affecting the determination of brain-derived neurotrophic factor (BDNF) in patients with stroke: a scoping review

Introduction: Brain-derived neurotrophic factor (BDNF) is a neurotrophin expressed in the central nervous system, where it supports synaptic plasticity, neuronal survival, and dendritic remodeling. Reduced circulating BDNF levels have been reported in several neurological and psychiatric disorders, increasing evidence links BDNF to post-stroke recovery. However, because BDNF is also produced and stored in platelets- the main peripheral reservoir- its measurement is highly sensitive to preanalytical handling. Improper sample preparation may trigger platelet degranulation and cause substantial variability in serum and plasma BDNF levels. Content: This scoping review examined preanalytical procedures used for BDNF quantification in clinical studies involving adult stroke patients. Following PRISMA-ScR guidelines, we systematically searched Pubmed, Embase, Web of Science, and the Cochrane Library for English-language clinical trials, randomized controlled trials, and observational studies measuring BDNF in blood derivatives. The search was completed on February 3rd, 2025. Summary: From 11,030 records identified, 8,696 underwent screening after removing duplicates and excluding records concerning populations other than stroke, 49 studies met inclusion criteria. 74.4 % reported associations between circulating BDNF levels and clinical features or outcomes, though significant heterogeneity across study designs limited comparability. Serum was used in 36 studies, but key preanalytical parameters (such as clotting time, transport temperature) were frequently unreported. Similar inconsistencies emerged for plasma preparation, including anticoagulant type and management of platelet content. Outlook: These findings reveal major gaps in the reporting of preanalytical methods for BDNF measurement in stroke research and emphasize the need for standardized procedures to ensure reliable and comparable biomarker data.