Spinal cord injury: molecular mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 26, 2023

Abstract Spinal cord injury (SCI) remains a severe condition with an extremely high disability rate. The challenges of SCI repair include its complex pathological mechanisms and the difficulties neural regeneration in central nervous system. In past few decades, researchers have attempted to completely elucidate mechanism identify effective strategies promote axon circuit remodeling, but results not been ideal. Recently, new SCI, especially interactions between immune cell responses, revealed by single-cell sequencing spatial transcriptome analysis. With development bioactive materials stem cells, more attention has focused on forming intermediate networks reconstruction than promoting axonal corticospinal tract. Furthermore, technologies control physical parameters such as electricity, magnetism ultrasound constantly innovated applied fate regulation. Among these advanced novel technologies, therapy, biomaterial transplantation, electromagnetic stimulation entered into stage clinical trials, some them already treatment. this review, we outline overall epidemiology pathophysiology expound latest research progress related detail, propose future directions for applications.

Language: Английский

---

Central nervous system regeneration

Cell, Journal Year: 2022, Volume and Issue: 185(1), P. 77 - 94

Published: Jan. 1, 2022

Language: Английский

---

Microglia coordinate cellular interactions during spinal cord repair in mice

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 14, 2022

Traumatic spinal cord injury (SCI) triggers a neuro-inflammatory response dominated by tissue-resident microglia and monocyte derived macrophages (MDMs). Since activated MDMs are morphologically identical express similar phenotypic markers in vivo, identifying responses specifically coordinated has historically been challenging. Here, we pharmacologically depleted use anatomical, histopathological, tract tracing, bulk single cell RNA sequencing to reveal the cellular molecular SCI controlled microglia. We show that vital for recovery coordinate CNS-resident glia infiltrating leukocytes. Depleting exacerbates tissue damage worsens functional recovery. Conversely, restoring select microglia-dependent signaling axes, identified through data, mice prevents secondary promotes Additional bioinformatics analyses optimal repair after might be achieved co-opting key ligand-receptor interactions between microglia, astrocytes MDMs.

Language: Английский

---

Regulation of axonal regeneration after mammalian spinal cord injury

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(6), P. 396 - 413

Published: Jan. 5, 2023

Language: Английский

---

Progression in translational research on spinal cord injury based on microenvironment imbalance

Bone Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: April 8, 2022

Spinal cord injury (SCI) leads to loss of motor and sensory function below the level imposes a considerable burden on patients, families, society. Repair injured spinal has been recognized as global medical challenge for many years. Significant progress made in research pathological mechanism injury. In particular, with development gene regulation, cell sequencing, tracing technologies, in-depth explorations SCI microenvironment have become more feasible. However, translational studies related repair not yielded significant results. This review summarizes latest two aspects pathology: intraneuronal imbalance regenerative imbalance. We also strategies based imbalance, including medications, transplantation, exosomes, tissue engineering, reprogramming, rehabilitation. The current state future directions are discussed. combined, precise, multitemporal strategy repairing is potential direction.

Language: Английский

---

Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: March 2, 2022

Spinal cord injury (SCI) involves diverse responses in different cell types a temporally and spatially specific manner. Here, using single-cell transcriptomic analyses combined with classic anatomical, behavioral, electrophysiological analyses, we report, resolution, temporal molecular cellular changes crush-injured adult mouse spinal cord. Data revealed pathological of 12 major types, three which infiltrated into the at distinct times post-injury. We discovered novel microglia astrocyte subtypes uninjured cord, their dynamic conversions additional stage-specific subtypes/states. Most occur 3-days post-injury by day-14 second wave microglial activation emerged, accompanied various including neurons, indicative round attacks. By day-38, are still substantially deviated from states, demonstrating prolonged alterations. This study provides comprehensive mapping cellular/molecular along axis after SCI, may facilitate development therapeutic strategies, those targeting microglia.

Language: Английский

---

Emerging roles for CNS fibroblasts in health, injury and disease

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 23(1), P. 23 - 34

Published: Oct. 20, 2021

Language: Английский

---

An NIR photothermal-responsive hybrid hydrogel for enhanced wound healing

Bioactive Materials, Journal Year: 2022, Volume and Issue: 16, P. 162 - 172

Published: March 10, 2022

Language: Английский

---

New insights into glial scar formation after spinal cord injury

Cell and Tissue Research, Journal Year: 2021, Volume and Issue: 387(3), P. 319 - 336

Published: June 2, 2021

Abstract Severe spinal cord injury causes permanent loss of function and sensation throughout the body. The trauma a multifaceted torrent pathophysiological processes which ultimately act to form complex structure, permanently remodeling cellular architecture extracellular matrix. This structure is traditionally termed glial/fibrotic scar. Similar formations occur following stroke, infection, neurodegenerative diseases central nervous system (CNS) signifying their fundamental importance preservation function. It increasingly recognized that scar performs multiple roles affecting recovery traumatic injury. Innovative research into properties this imperative development treatment strategies recover motor CNS trauma. In review, we summarize how regeneration potential alters across phyla age through formation scar-like structures. We describe new insights from next-generation sequencing technologies have yielded more portrait molecular mechanisms governing astrocyte, microglial, neuronal responses development, especially glial component Finally, discuss possible combinatorial therapeutic approaches centering on modulation restore after severe

Language: Английский

---

Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells

Neuron, Journal Year: 2022, Volume and Issue: 110(16), P. 2625 - 2645.e7

Published: June 28, 2022

Language: Английский

---