Fujian Tablets promote corticospinal tract remodeling and improve motor function in MCAO rats by regulating BDNF...

Fujian Tablets (FJT), a traditional Chinese medicinal (TCM) preparation, has been clinically used in the rehabilitation of neurological disorders related to ischemic brain injury in the context of TCM theory. However, its molecular mechanism underlying the promotion of post-ischemic stroke motor function recovery, especially via regulating corticospinal tract (CST) remodeling-a key structure for motor control-remains unelucidated.

This study aimed to investigate the effect of FJT on CST remodeling in the denervated hemisphere and motor function recovery in middle cerebral artery occlusion (MCAO) rats, and to explore its potential mechanism by focusing on the balance between precursor brain-derived neurotrophic factor (proBDNF) and mature BDNF (mBDNF), which is tightly regulated by BDNF-cleaving enzymes (Pcsk1 and Furin).

The MCAO rat model was established using the intraluminal filament method. Model rats were randomly divided into four groups: MCAO model group, FJT low-dose group, FJT medium-dose group, and FJT high-dose group. Motor function was evaluated by Catwalk gait analysis (assessing average speed, step length, and standing time). CST remodeling and conduction efficiency were determined via biotinylated dextran amine (BDA) neural tracing and motor evoked potential (MEP) detection, respectively. The mRNA and protein expressions of BDNF, cleaving enzymes (Pcsk1, Furin), and related receptors (TrkB, p75NTR, Sortilin) in brain tissues were measured using quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. BDNF silencing experiment was performed to verify the role of BDNF in FJT-induced effects. Additionally, in vitro neuronal culture was used to observe the effects of FJT, exogenous mBDNF, and Pcsk1/Furin inhibitors on neuronal growth.

Compared with the MCAO model group, medium-dose FJT exhibited the most significant therapeutic effects. Specifically, FJT notably improved gait parameters increasing average speed from 20.77 mm/s (MCAO) to 25.71 mm/s (FJT) and step length by approximately 21.14 %. Furthermore, FJT enhanced MEP conduction efficiency and promoted CST remodeling, characterized by a 5.26 % increase in BDA-positive nerve fibers and elevated growth-associated protein 43 (GAP43) expression in the denervated hemisphere. At the molecular level, FJT upregulated the mRNA and protein expressions of Pcsk1 and Furin, increased the levels of BDNF and its functional receptor TrkB, and downregulated the expressions of proBDNF-preferring receptors p75NTR and Sortilin, ultimately shifting the proBDNF/mBDNF ratio toward mBDNF dominance. BDNF silencing significantly attenuated these improvements, reversing FJT-induced motor recovery and CST remodeling. In vitro, FJT-promoted neuronal growth was mimicked by exogenous mBDNF but reversed by Pcsk1/Furin inhibitors.

Compared with the MCAO model group, medium-dose FJT exhibited the most significant therapeutic effects. Specifically, FJT notably improved gait parameters, increasing the average speed from 20.77 mm/s (MCAO) to 25.71 mm/s (FJT) and step length by approximately 21.14 %. Furthermore, FJT enhanced MEP conduction efficiency and promoted CST remodeling, characterized by a 5.26% increase in BDA-positive nerve fibers and elevated Growth-Associated Protein 43 (GAP43) expression in the denervated hemisphere. At the molecular level, FJT upregulated the mRNA and protein expressions of Pcsk1 and Furin, increased the levels of BDNF and its functional receptor TrkB, and downregulated the expressions of proBDNF-preferring receptors p75NTR and Sortilin, ultimately shifting the proBDNF/mBDNF ratio toward mBDNF dominance. BDNF silencing significantly attenuated these improvements, reversing FJT-induced motor recovery and CST remodeling. In vitro, FJT-promoted neuronal growth was mimicked by exogenous mBDNF but reversed by Pcsk1/Furin inhibitors.