Ischemic stroke, characterized by sudden interruption of cerebral blood flow, is the leading global cause of disability, affecting approximately 7.6 million people annually and with a prevalence exceeding 77 million worldwide. Among these patients, around 80 % experience persistent limb motor dysfunction (Stokowska A et al., 2023; Dawson J et al., 2021). Despite advances in thrombolytic and endovascular therapies, over 60 % of survivors still exhibit chronic motor deficits. Persistent motor impairments correlate with reduced quality of life and increased socioeconomic burdens (Zong X et al., 2022; Wang A et al., 2024).

The subacute to chronic recovery phase of ischemic stroke is marked by dynamic neuroplasticity driven by endogenous repair mechanisms (Baig SS et al., 2023). The corticospinal tract (CST), the primary neural pathway for cortical control of limb movement, is critical for motor function recovery (Daghsen L et al., 2024; Hosp JA et al., 2023; Zhang et al., 2022b). After stroke-induced damage to the ipsilateral CST, intact CST fibers from the contralateral hemisphere extend axons through the cervical spinal cord, forming functional circuits with denervated spinal motor neurons via cross-hemispheric neuroplasticity (Yang Y et al., 2024; Buetefisch CM et al., 2023). Thus, promoting ipsilateral CST remodeling by facilitating sprouting and synaptic integration of contralateral CST axons has become a research focus.

Following significant tissue loss, CST functional recovery relies on spontaneous compensatory reorganization, but endogenous adaptability is often limited by insufficient axonal regeneration and inhibitory microenvironments, hindering midline crossing and synaptic formation with denervated spinal neurons[ Wu C et al., 2024; Li J et al., 2023; Wan H et al., 2024]. Brain-derived neurotrophic factor (BDNF) serves as a core mediator in the remodeling of the CST following central nervous system (CNS) injury (Wang et al., 2023; Ozdinler and Macklis, 2006). Upon focal disruption of the unilateral sensorimotor cortex, intact CST axons undergo de novo sprouting within specific laminae of the cervical denervated spinal cord and form functional synaptic connections with two distinct subpopulations of spinal interneurons: segmental interneurons and propriospinal neuronsp [Ueno M et al., 2012]. This newly established corticospinal-interneuronal circuitry is indispensable for the recovery of motor function, as selective ablation of this circuit precipitates persistent impairment in forelimb motor performance during the post-injury recovery phase [Wu D et al., 2025]. BDNF enhances synaptic stabilization, axon sprouting, and neurogenesis via activation of tropomyosin receptor kinase B (TrkB) (Tanaka T et al., 2020).

Notably, precursor brain-derived neurotrophic factor (proBDNF) and mature BDNF (mBDNF) exert bidirectionally antagonistic functions in neural regulation: proBDNF binds to the p75 neurotrophin receptor (p75NTR) to trigger synaptic pruning, neuronal apoptosis, and inhibit axonal regeneration and synaptic plasticity; in contrast, mBDNF selectively activates the tyrosine kinase receptor B (TrkB) pathway to enhance positive neuroplasticity, including neurite outgrowth, axonal sprouting, and functional synaptic formation (Chen R et al., 2025; Wang D et al., 2024). This critical functional balance is primarily tightly regulated by two core BDNF-cleaving enzymes—proprotein convertase (PC) and furin—which mediate the proteolytic cleavage of proBDNF into bioactive mBDNF within the Golgi apparatus or secretory vesicles (Guo J et al., 2016; Zhang Y et al., 2022). As the rate-limiting step in mBDNF biosynthesis, this process determines the levels of bioactive mBDNF and the proBDNF/mBDNF ratio—a key switch governing the outcome of neural remodeling after injury. Reduced PC/furin activity slows down cleavage, leading to proBDNF accumulation and inhibition of neural growth via p75NTR overactivation; conversely, increased activity promotes mBDNF production and TrkB-mediated axonal sprouting (Yang CR et al., 2024; Mitrovic M et al., 2025; Diniz et al., 2025; Martinowich K et al., 2007).

Remodeling of the CST is widely recognized as the core cellular basis for motor function recovery following stroke [Wang Y et al., 2023]. However, the endogenous neurorepair capacity is often insufficient to achieve satisfactory motor function recovery, highlighting the necessity of developing effective therapeutic interventions to enhance CST remodeling. Traditional Chinese Medicine (TCM) offers novel insights for enhancing endogenous repair strategies (Fan et al., 2024). The TCM rehabilitation concept of “nourishing the liver and kidney, replenishing essence, and unblocking marrow” aligns conceptually with modern therapeutic goals of enhancing neuroplasticity (Liu, 2013). In this context, Fujian Tablet (FJT)—formulated with Hippocampus, Cassiae Semen, Polygonum Multiflorum Preparata, Viscum Coloratum, and Epimedii Folium—serves as a potent clinically used formula for “invigorating the kidney and unblocking collaterals”.Previous studies have already demonstrated that FJT can promote axonal outgrowth in the denervated cervical spinal cord (Gao et al., 2026, Liu et al., 2018, Liu et al., 2019). However, the specific molecular pathways translating this macroscopic “collateral-unblocking” efficacy into CST remodeling remain to be fully elucidated. We propose that the TCM principle of alleviating meridian obstruction parallels the biological necessity of overcoming molecular inhibitors of regeneration—specifically, the restoration of the proBDNF/mBDNF balance. We hypothesize that FJT acts by upregulating the expression of Pcsk1/Furin to facilitate the proteolytic cleavage of proBDNF into mBDNF. This optimization of the proBDNF/mBDNF equilibrium is postulated to activate the TrkB-mediated neurorepair signaling pathway, thereby driving CST remodeling and motor function recovery after ischemic stroke.