Neural Regeneration Research最新文献

JOURNAL/nrgr/04.03/01300535-202605000-00041/figure1/v/2025-10-21T121913Z/r/image-tiff Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death. Although extensive research has been conducted on neuroprotection for retinal ganglion cells, there is still no treatment for clinical use. Recent evidence shows that extracellular vesicles isolated from a variety of stem cells are efficacious in retinal ganglion cell neuroprotection. In this study, we tested the novel extracellular vesicle source of the retinal progenitor R-28 cell line in vitro and in vivo . We isolated and characterized extracellular vesicles from R-28 cells and tested their therapeutic efficacy in terms of retinal ganglion cell survival in vitro and in an in vivo glaucoma model, measuring retinal ganglion cell survival and preservation of their axons. Additionally, we tested extracellular vesicles for their neuroprotective capacity in retinal ganglion cells differentiated from human embryonic stem cells. Finally, we investigated miRNA changes in retinal ganglion cells with R-28 extracellular vesicle treatment, and predicted possible pathways that may be modulated. R-28 extracellular vesicles improved retinal ganglion cell survival but failed to preserve axons significantly. Moreover, the results also illustrated the neuroprotection of R-28 extracellular vesicles on human retinal ganglion cells. Finally, we also showed changes in hsa-miRNA-4443, hsa-miRNA-216a-5p, hsa-let-7e-5p, hsa-miRNA-374b-5p, hsa-miRNA-331-3p, and hsa-miRNA-421 expressions, which may have neuroprotective potential on retinal ganglion cell degeneration. This study will pave the way for miRNA and extracellular vesicle-based neuroprotective therapies for glaucoma.

Stroke is a major cause of death and disability worldwide. It is characterized by a highly interconnected and multiphasic neuropathological cascade of events, in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury. Neuroinflammation, a key player in the pathophysiology of stroke, has a dual role. In the acute phase of stroke, neuroinflammation exacerbates brain injury, contributing to neuronal damage and blood-brain barrier disruption. This aspect of neuroinflammation is associated with poor neurological outcomes. Conversely, in the recovery phase following stroke, neuroinflammation facilitates brain repair processes, including neurogenesis, angiogenesis, and synaptic plasticity. The transition of neuroinflammation from a harmful to a reparative role is not well understood. Therefore, this review seeks to explore the mechanisms underlying this transition, with the goal of informing the development of therapeutic interventions that are both time- and context-specific. This review aims to elucidate the complex and dual role of neuroinflammation in stroke, highlighting the main actors, biomarkers of the disease, and potential therapeutic approaches.

Synaptic pruning is a crucial process in synaptic refinement, eliminating unstable synaptic connections in neural circuits. This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms. The pruning process involves multiple molecular signals and a series of regulatory activities governing the "eat me" and "don't eat me" states. Under physiological conditions, the interaction between glial cells and neurons results in the clearance of unnecessary synapses, maintaining normal neural circuit functionality via synaptic pruning. Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning, thus promoting the occurrence and development of autism spectrum disorder, schizophrenia, Alzheimer's disease, and other neurological disorders. In this review, we investigated the molecular mechanisms responsible for synaptic pruning during neural development. We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders. Furthermore, we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function, as well as their potential for clinical translation. Our aim was to enhance our understanding of synaptic pruning during neural development, including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density, and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases, thus providing a theoretical foundation for the treatment of neurological disorders.

Research into lactylation modifications across various target organs in both health and disease has gained significant attention. Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications. Lactate, once considered merely a byproduct of anaerobic metabolism, has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system. Furthermore, recent studies have emphasized the significant role of lactate in numerous neurological diseases, including Alzheimer's disease, Parkinson's disease, acute cerebral ischemic stroke, multiple sclerosis, Huntington's disease, and myasthenia gravis. The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases, aiming to clarify their mechanisms of action and identify potential therapeutic targets. As such, this work provides an overview of the metabolic regulatory roles of lactate in various disorders, emphasizing its involvement in the regulation of brain function. Additionally, the specific mechanisms of brain lactate metabolism are discussed, suggesting the unique roles of lactate in modulating brain function. As a critical aspect of lactate function, lactylation modifications, including both histone and non-histone lactylation, are explored, with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications, such as lactylation writers and erasers. The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized, revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders. Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.

JOURNAL/nrgr/04.03/01300535-202605000-00038/figure1/v/2025-10-21T121913Z/r/image-tiff Nonhuman primates are increasingly being used as animal models in neuroscience research. However, efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking. Here, by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey, we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord. Labeled alpha motor neurons were located in lamina IX of the L6-S1 segments, which innervate both flexors and extensors. The labeled primary sensory afferents were mainly myelinated Aβ fibers that terminated mostly in laminae I and II of the L4-L7 segments. Together with the labeled proprioceptive afferents, the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons. In summary, our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.