Functional optic tract rewiring via subtype- and target-specific axonal regeneration and presynaptic activity enhancement DOI Creative Commons
Xin Zhang, Chao Yang, Chengle Zhang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 4, 2025

Mechanisms underlying functional axonal rewiring after adult mammalian central nervous system (CNS) injuries remain unclear partially due to limited models. Here we develop a mouse intracranial pre-olivary pretectal nucleus (OPN) optic tract injury model and demonstrate that Pten/Socs3 knockout CNTF expression in retinal ganglion cells (RGCs) promotes regeneration OPN reinnervation. Revealed by transmission electron microscopy, trans-synaptic labeling, electrophysiology, synapses are formed mainly intrinsically photosensitive RGCs, thereby restoring the pupillary light reflex (PLR). Moreover, combining with Lipin1 knockdown accelerates recovery achieves reconnection chronic injury. PLR can be further boosted increasing RGC photosensitivity melanopsin overexpression, it also enhanced treatment of voltage-gated calcium channel modulator augment presynaptic release. These findings highlight importance neuronal types activity for CNS injuries.

Language: Английский

An esterase-activatable nanoprodrug mitigates severe spinal cord injury via alleviating ferroptosis and reprogramming inflammatory microenvironment DOI
Jinggong Liu,

Yanzhou Chang,

Wen Zhou

et al.

Nano Today, Journal Year: 2024, Volume and Issue: 56, P. 102229 - 102229

Published: March 16, 2024

Language: Английский

Citations

5
Advances in electroactive bioscaffolds for repairing spinal cord injury DOI
Zeqi Liu,

Jiahui Lai,

Dexin Kong

et al.

Biomedical Materials, Journal Year: 2024, Volume and Issue: 19(3), P. 032005 - 032005

Published: April 18, 2024

Spinal cord injury (SCI) is a devastating neurological disorder, leading to loss of motor or somatosensory function, which the most challenging worldwide medical problem. Re-establishment intact neural circuits basis spinal regeneration. Considering crucial role electrical signals in nervous system, electroactive bioscaffolds have been widely developed for SCI repair. They can produce conductive pathways and pro-regenerative microenvironment at lesion site similar that natural cord, neuronal regeneration axonal growth, functionally reactivating damaged circuits. In this review, we first demonstrate pathophysiological characteristics induced by SCI. Then, repair introduced. Based on comprehensive analysis these characteristics, recent advances are summarized, focusing both piezoelectric bioscaffolds, used independently combination with external electronic stimulation. Finally, thoughts challenges opportunities may shape future concluded.

Language: Английский

Citations

5
A sequential stimuli-responsive hydrogel promotes structural and functional recovery of severe spinal cord injury DOI
Chen Hu,

Wanshun Wang,

Yiming Yang

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 316, P. 122995 - 122995

Published: Dec. 6, 2024

Language: Английский

Citations

4
Axon regeneration after spinal cord and brain injuries DOI

Madeline Rose McCrea,

Shuxin Li

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 315 - 346

Published: Jan. 1, 2025

Language: Английский

Citations

0
Fecal microbiota transplantation promotes functional recovery in mice with spinal cord injury by modulating the spinal cord microenvironment DOI Creative Commons

Huan Xie,

Hui Zhang,

Liyi Zhou

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 20, 2025

spinal cord injury (SCI) disrupts the gut microbiota, worsening injury's impact. Fecal microbiota transplantation (FMT) is increasingly recognized as a promising strategy to improve neural function post-SCI, yet its precise mechanisms are still far from clear. The present study aims elucidate how FMT influences motor recovery and underlying utilizing SCI mouse model. Mice with received healthy donors. We used 16 S rRNA amplicon sequencing analyze alterations of microbes. Pathological in tissue, including neuronal survival, axonal regeneration, cell proliferation, neuroinflammation, were assessed among experimental groups. Additionally, RNA (RNA-seq) was explore relevant signaling pathways. Significant shifts composition following observed through analysis. On day 7 group exhibited significantly higher diversity compared ABX group, more closely resembling that mice. promoted survival leading notable improvements control Immunofluorescence staining showed increased alleviated extracellular matrix (ECM) deposition, diminished glial scar formation, reduced inflammation FMT-treated RNA-seq analysis indicated induced transcriptomic changes associated material metabolism, ECM remodeling, anti-inflammatory responses. restored balance mice, mitigated inflammation, establishing an optimal environment for recovery. These findings demonstrated may represent valuable approach enhance functional SCI.

Language: Английский

Citations

0
Conjugated therapy with coaxially printed neural stem cell-laden microfibers and umbilical cord mesenchymal stem cell derived exosomes on complete transactional spinal cord defects DOI Creative Commons
Xinda Li,

Jin Zhang,

Yi Zhang

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 32, P. 101639 - 101639

Published: March 4, 2025

Motor function recovery after complete spinal cord injury remained as a challenge in medical field, while one of the key approaches is promoting local microenvironments. In this research, we performed conjugated therapy by transplantation neural stem cell (NSC) scaffolds and umbilical mesenchymal derived exosomes (ucMSC-exos) for treatment transactional (SCI). We first demonstrated anti-inflammatory effects ucMSC-exos vitro found that could regulate microglia polarization from M1 to M2, an phenotype. Besides, also promoted NSC proliferation differentiation during culturing. On other hand, core-shell hydrogel microfibers were used both small large SCI defects. The carry amounts NSCs core portion shell highly permeable nutrient metabolite transportation. vivo experiments, decreased inflammatory cytokines at lesion sites, gave rise more neurons angiogenesis, thus comprehensively improved microenvironment compared with only. These beneficial results accordance those experiments further led better locomotor recovery. summary, research has make potential tool repair.

Language: Английский

Citations

0
Succinic acid-based biodegradable hydrogels drive Bv2 microglial polarization by ATP metabolism DOI
Jingwen Zhao, Yongqiang Xiong, Xinying Wang

et al.

Composites Part B Engineering, Journal Year: 2025, Volume and Issue: unknown, P. 112383 - 112383

Published: March 1, 2025

Language: Английский

Citations

0
Self‐Enhancing Drug Pair‐Driven Selenium Nanotherapeutics Reverses Microglial Pyroptosis Through NLRP3/Caspase‐1 Pathway and Neuronal Apoptosis for Treatment of Spinal Cord Injury DOI Open Access

Jinggong Liu,

Luo-Qi Mai,

Aaron C. Tan

et al.

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 23, 2025

Abstract Spinal cord injury (SCI) constitutes a critical occurrence that results in the disruption of both motor and sensory functions. Oxidative stress‐induced apoptosis pyroptosis have been identified as contributors to neuronal damage during secondary phase following SCI. Therefore, this study focuses on development self‐enhancing drug pair‐driven selenium (Se) nanotherapeutics, loading with 2,3,5,6‐tetramethylpyrazine (TMP) Ginsenoside Rg1 (Rg1), enhance treatment The engineered LET/TMP/Rg1@Se NPs exhibits remarkable antioxidant properties, effectively reducing oxidative by minimizing reactive oxygen species (ROS) accumulation restoring mitochondrial function. In addition their effects, nanotherapeutics demonstrates significant anti‐pyroptotic effects BV2 microglial cells modulating NLRP3/caspase‐1 pathway, leading decreased release pro‐inflammatory cytokines IL‐1β IL‐18. Moreover, inhibition inflammatory cascade response diminishes neuroinflammation‐induced promotes axonal regeneration neurons vitro. mouse model SCI, improved function regeneration, attributed pyroptosis, highlighting scientific basis for synergistic effect Se an innovative strategy effective SCI therapy.

Language: Английский

Citations

0
Activation of hypothalamic-pontine-spinal pathway promotes locomotor initiation and functional recovery after spinal cord injury in mice DOI Creative Commons
Yi Li,

Chengyue Ji,

Y. Zhang

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Abstract The hypothalamus is critical for regulating behaviors essential survival and locomotion, but how it integrates internal needs transmits locomotion commands to the spinal cord (SC) remains unclear. We found that glutamatergic neurons in lateral hypothalamic area (LHA) are motivated locomotor activity. Using single-neuron projectome analysis, trans-synaptic tracing, optogenetic manipulation, we showed LHA facilitates during food seeking via pontine oral part (PnO) projection neurons, rather than direct SC projections or indirect stress signaling medial septum diagonal band. Activating PnO-SC also initiated locomotion. Importantly, LHA-PnO were crucial recovery following mouse injury (SCI). Motor cortex signals gated deep brain stimulation treatment markedly promoted long-term restoration of hindlimb motor functions after severe SCI. Thus, have identified a hypothalamic-pontine-spinal pathway paradigm potential therapeutic intervention

Language: Английский

Citations

0
Engineering neuroregenerative microenvironment via aligned hydrogel-assisted magnetic stimulation for complete spinal cord injury repair DOI Creative Commons
Chun-Yi Yang, Zhe Meng,

Zhijun He

et al.

Engineered Regeneration, Journal Year: 2024, Volume and Issue: 5(2), P. 139 - 152

Published: Feb. 3, 2024

Utilizing biomaterials in tissue engineering has shown considerable promise for regeneration, particularly through delivering a range of cell-regulatory signals, both inherent to the material and external. In this research, we developed magnetic-responsive aligned nanofiber fibrin hydrogel (MAFG), integrating structured alignment nanofibers pliability with an external magnetic field. This design aimed enhance regenerative response spinal cord injury treatment. A medium-strength field, cord, was applied aid motor function recovery rats injuries. The use MAFG context not only intensified effect field but also encouraged activation differentiation native neural stem cells. Furthermore, method effectively steered macrophage polarization towards beneficial M2 phenotype, addressing immune dysregulation at site. parallel application stimulation model contributed concurrent promotion neurogenesis, angiogenesis, immunomodulation, resulting marked improvement rats. investigation underscores therapeutic potential highlights how aligning can significantly milieu

Language: Английский

Citations

3