Clinically, individualized training improves post-stroke motor function rehabilitation efficiency. However, the mechanisms underlying how individualized training facilitates recovery remain relatively unclear. Here, we explored the cortical and corticomuscular rehabilitative effects of post-stroke motor function recovery during individualized training using a rat model of intracerebral hemorrhage. Forced training or individualized fatigue-controlled training was provided from days 2 to 14 post-stroke. The fatigue-controlled training group exhibited superior motor function recovery and less central fatigue compared with the forced training group. Electroencephalograph power spectrum density slope analysis demonstrated better inter-hemispheric balance in the fatigue-controlled training group than in the forced training group. Directed corticomuscular coherence analysis indicated that training-induced fatigue led to a short-term downregulation of descending directed corticomuscular coherence and an upregulation of ascending directed corticomuscular coherence. In the long term, excessive fatigue hindered the recovery of descending control in the affected hemisphere. In conclusion, the individualized strategy of peripheral fatigue-controlled training achieved better motor function recovery, which may be attributed to the mitigation of central fatigue, optimization of inter-hemispheric balance, and enhancement of descending control in the affected hemisphere. This is the first study to investigate the mechanisms underlying individualized rehabilitative effects at the cortical and corticomuscular levels. Our findings suggest that personalized training protocols that are tailored to manage fatigue levels may substantially enhance post-stroke motor efficiency. They also provide a mechanistic foundation for developing fatigue-monitored, individualized rehabilitation programs in clinical practice.

Patients with spinal cord injury frequently develop neurogenic heterotopic ossification, whose pathogenesis remains incompletely understood. Existing research models struggle to accurately simulate the complex pathological process. To establish a reliable neurogenic heterotopic ossification research model, elucidate its pathogenesis, and explore early intervention strategies, this study successfully developed a spinal cord injury-induced neurogenic heterotopic ossification mouse model. Significant ectopic bone formation, restricted hip and knee joint mobility, and motor dysfunction were observed, accompanied by elevated expression of the osteogenic markers alkaline phosphatase, runt-related transcription factor 2, sex-determining region Y-box 9, and osteocalcin . Proteomics and quantitative polymerase chain reaction analysis revealed upregulation of chemokine (C-X-C motif) ligand (CXCL)12, C-X-C chemokine receptor type 4 (CXCR4), and LYN proto-oncogene, whereas CXCL1 was downregulated in the neurogenic heterotopic ossification group. In vivo experiments confirmed abnormal accumulation of M1 macrophages in muscles surrounding early ectopic bone tissue, with markedly elevated CXCL12 expression. In vitro studies further revealed that M1 macrophages are the primary source of CXCL12 secretion, and their cell culture supernatants promote the proliferation, migration, and osteoblastic differentiation potential of bone marrow mesenchymal stem cells. Mechanistically, CXCL12 activates the phosphatidylinositol 3-kinase/protein kinase B pathway by binding to the CXCR4 receptor, thereby driving the osteogenic differentiation of bone marrow mesenchymal stem cells. These findings indicate a causal relationship between the pathological process of neurogenic heterotopic ossification following spinal cord injury and the activation of the CXCL12-CXCR4-phosphatidylinositol 3-kinase-protein kinase B signaling axis, which modulates bone marrow mesenchymal stem cell function through M1 macrophage polarization. This study reveals a key mechanism driving the osteogenic differentiation of bone marrow mesenchymal stem cells, providing new directions for early warning and targeted treatment of neurogenic heterotopic ossification following spinal cord injury.

Oxidative stress and lysosomal dysfunction are considered as critical contributors to epileptogenesis and its progression. These processes create a self-perpetuating cycle that worsens neuronal hyperexcitability, neuroinflammation, and synaptic pathology, while simultaneously impairing neural stem cell survival and neuroregeneration, which includes neurogenesis, synaptic remodeling, and circuit repair. Traditional treatments merely suppress discharges but overlook the synaptic damage, loss of inhibitory interneurons, and exhaustion of neural stem cells caused by oxidative stress and lysosomal dysfunction, making it difficult for the network structure to self-repair. The purpose of this review is to explore a new paradigm "Restarting synaptic remodeling and structural network: A novel strategy for neuroregeneration in epilepsy." This review clearly outlines the mechanisms through which oxidative stress and lysosomal dysfunction damage synapses, neurons, and neural stem cells, as well as the reinforcing feedback loop that these two processes create within the epileptic network. In terms of nerve repair, a "dual-target repair" strategy can be implemented. On one hand, this involves using an activator of nuclear factor erythroid 2-related factor 2 combined with antioxidants to eliminate reactive oxygen species and protect existing synapses. On the other hand, it includes employing transcription factor EB agonists, mTOR inhibitors, or gene/enzyme replacement therapies to restore lysosomal degradation function, clear aggregates, and rebuild the inhibitory microenvironment. Taken together, the oxidative stress-lysosomal dysfunction-neuroregeneration axis provides a unifying framework that integrates molecular pathology with failed neural repair, offering a novel perspective for developing next-generation therapies aimed at both seizure reduction and circuit restoration. This paradigm shift emphasizes the potential of neuroregenerative strategies to restart synaptic remodeling and repair structural network in epilepsy and related neurodegenerative disorders.

The nucleus, as the largest organelle within the cell, serves as the central hub for storing, replicating, and transcribing genetic information, thereby orchestrating vital cellular processes. In eukaryotic cells, the nuclear membrane is composed of several structural components: the outer and inner nuclear membranes, the nuclear pore complexes, and the underlying nuclear lamina, which together preserve the stability of the intracellular environment. Neurodegenerative disorders, such as Alzheimer's disease and related dementias, are characterized by the gradual degeneration and loss of neuronal structure and function in the central nervous system. Growing evidence suggests that alterations in nuclear envelope architecture are closely associated with the onset and progression of these diseases. This article summarizes the information, focusing on the regulators of the cell nuclear membrane, as well as its pathophysiological processes and regulatory mechanisms in neurodegenerative diseases. Moreover, this paper discusses related research advances that provide novel insights into a deeper understanding of the nuclear membrane in disease progression and its potential as a therapeutic target.