Misguidance and modulation of axonal regeneration by Stat3 and Rho/ROCK signaling in the transparent optic nerve DOI Creative Commons
Vincent Pernet,

Sandrine Joly,

Noémie Jordi

et al.

Cell Death and Disease, Journal Year: 2013, Volume and Issue: 4(7), P. e734 - e734

Published: July 18, 2013

The use of the visual system played a major role in elucidation molecular mechanisms controlling axonal regeneration injured CNS after trauma. In this model, CNTF was shown to be most potent known neurotrophic factor for optic nerve. To clarify downstream growth regulator Stat3, we analyzed and neuronal survival an nerve crush adult mice. infection retinal ganglion cells with adeno-associated virus serotype 2 (AAV2) containing wild-type (Stat3-wt) or constitutively active (Stat3-ca) Stat3 cDNA promoted Axonal whole-mounted nerves three dimensions (3D) tissue clearing. Surprisingly, AAV2.Stat3-ca stimulation, axons elongating beyond lesion site displayed very irregular courses, including frequent U-turns, suggesting massive directionality guidance problems. pharmacological blockade ROCK, key signaling component myelin-associated inhibitors, reduced U-turns potentiated AAV2.Stat3-ca-induced regeneration. Similar results were obtained sustained delivery axotomized retina. These show important activation program regeneration, they reveal that misguidance is limiting can affect long-distance target interaction trauma CNS. correction associated improved axon

Language: Английский

Immune response following traumatic spinal cord injury: Pathophysiology and therapies DOI Creative Commons
Robert C. Sterner, Rosalie M. Sterner

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 6, 2023

Traumatic spinal cord injury (SCI) is a devastating condition that often associated with significant loss of function and/or permanent disability. The pathophysiology SCI complex and occurs in two phases. First, the mechanical damage from trauma causes immediate acute cell dysfunction death. Then, secondary mechanisms further propagate death over course days, weeks, or even months. Among mechanisms, inflammation has been shown to be key determinant severity significantly worsens functional outcomes. Thus, addition surgical management SCI, selectively targeting immune response following could substantially decrease progression improve patient In order develop such therapies, detailed molecular understanding timing necessary. Recently, several studies have mapped cytokine/chemokine proliferation patterns SCI. this review, we examine underlying assess both current future therapies including pharmaceutical stem therapy, exciting potential extracellular vesicle therapy.

Language: Английский

Citations

100
Shaping the brain vasculature in development and disease in the single-cell era DOI Open Access
Thomas Wälchli, Jeroen Bisschop, Peter Carmeliet

et al.

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(5), P. 271 - 298

Published: March 20, 2023

Language: Английский

Citations

74
Neuronal maturation and axon regeneration: unfixing circuitry to enable repair DOI
Brett J. Hilton, Jarred M. Griffin, James W. Fawcett

et al.

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(10), P. 649 - 667

Published: Aug. 20, 2024

Language: Английский

Citations

18
Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination DOI Open Access
Seon‐Ah Chong,

Sheila Rosenberg,

Stephen P.J. Fancy

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2011, Volume and Issue: 109(4), P. 1299 - 1304

Published: Dec. 12, 2011

A requisite component of nervous system development is the achievement cellular recognition and spatial segregation through competition-based refinement mechanisms. Competition for available axon space by myelinating oligodendrocytes ensures that all relevant CNS axons are myelinated properly. To ascertain nature this competition, we generated a transgenic mouse with sparsely labeled establish individual occupying similar tracts can greatly vary number lengths their myelin internodes. Here show intercellular interactions between competing oligodendroglia influence length internodes, referred to as myelinogenic potential, identify amino-terminal region Nogo-A, expressed oligodendroglia, necessary sufficient inhibit process. Exuberant expansive myelination/remyelination detected in absence Nogo during after demyelination, suggesting extent limited microenvironmental inhibition. We demonstrate unique physiological role Nogo-A precise myelination developing CNS. Maximizing potential may offer an effective strategy repair future therapies demyelination.

Language: Английский

Citations

217
Axon Regeneration Pathways Identified by Systematic Genetic Screening in C. elegans DOI Creative Commons
Lizhen Chen, Zhiping Wang, Anindya Ghosh‐Roy

et al.

Neuron, Journal Year: 2011, Volume and Issue: 71(6), P. 1043 - 1057

Published: Sept. 1, 2011

Language: Английский

Citations

198
Wiring the Vascular Network with Neural Cues: A CNS Perspective DOI Creative Commons
Thomas Wälchli,

Andrin Wacker,

Karl Frei

et al.

Neuron, Journal Year: 2015, Volume and Issue: 87(2), P. 271 - 296

Published: July 1, 2015

Language: Английский

Citations

165
The role of Nogo-A in axonal plasticity, regrowth and repair DOI
Vincent Pernet, Martin E. Schwab

Cell and Tissue Research, Journal Year: 2012, Volume and Issue: 349(1), P. 97 - 104

Published: May 15, 2012

Language: Английский

Citations

164
The Sphingolipid Receptor S1PR2 Is a Receptor for Nogo-A Repressing Synaptic Plasticity DOI Creative Commons
Anissa Kempf,

Bjoern Tews,

Michael E. Arzt

et al.

PLoS Biology, Journal Year: 2014, Volume and Issue: 12(1), P. e1001763 - e1001763

Published: Jan. 14, 2014

Nogo-A is a membrane protein of the central nervous system (CNS) restricting neurite growth and synaptic plasticity via two extracellular domains: Nogo-66 Nogo-A-Δ20. Receptors transducing Nogo-A-Δ20 signaling remained elusive so far. Here we identify G protein-coupled receptor (GPCR) sphingosine 1-phosphate 2 (S1PR2) as Nogo-A-Δ20-specific receptor. binds S1PR2 on sites distinct from pocket sphingolipid (S1P) signals G13, Rho GEF LARG, RhoA. Deleting or blocking counteracts Nogo-A-Δ20- myelin-mediated inhibition outgrowth cell spreading. Blockade strongly enhances long-term potentiation (LTP) in hippocampus wild-type but not Nogo-A−/− mice, indicating repressor function Nogo-A/S1PR2 axis plasticity. A similar increase LTP was also observed motor cortex after blockade. We propose novel model which GPCR functions for structurally unrelated ligands, sphingolipid. Elucidating platforms will provide new insights into regulation

Language: Английский

Citations

164
Role of Leucine-Rich Repeat Proteins in the Development and Function of Neural Circuits DOI
Joris de Wit, Weizhe Hong, Liqun Luo

et al.

Annual Review of Cell and Developmental Biology, Journal Year: 2011, Volume and Issue: 27(1), P. 697 - 729

Published: March 3, 2011

The nervous system consists of an ensemble billions neurons interconnected in a highly specific pattern that allows proper propagation and integration neural activities. organization these connections emerges from sequential developmental events including axon guidance, target selection, synapse formation. These critically rely on cell-cell recognition communication mediated by cell-surface ligands receptors. Recent studies have uncovered central roles for leucine-rich repeat (LRR) domain-containing proteins, not only organizing connectivity guidance to selection formation, but also various disorders. Their versatile LRR domains, particular, serve as key sites interactions with wide diversity binding partners. Here, we focus few exquisite examples secreted or membrane-associated proteins Drosophila mammals review the mechanisms which they regulate diverse aspects development function.

Language: Английский

Citations

155
Integrins and the extracellular matrix: Key mediators of development and regeneration of the sensory nervous system DOI
Natalie J. Gardiner

Developmental Neurobiology, Journal Year: 2011, Volume and Issue: 71(11), P. 1054 - 1072

Published: July 15, 2011

The somatosensory nervous system is responsible for the transmission of a multitude sensory information from specialized receptors in periphery to central system. Sensory afferents can potentially be damaged at several sites: peripheral nerve; dorsal root; or columns spinal cord; and success regeneration depends on site injury. nerve branches following injury relatively successful compared branches. This largely attributed presence neurotrophic factors Schwann cell basement membrane rich permissive extracellular matrix (ECM) components which promote axonal nerve. Modulation ECM environment and/or neuronal integrins may enhance regenerative potential neurons disease. review describes interactions between molecules (particularly growth supportive ligands, laminin, fibronectin; inhibitory chondroitin sulfate proteoglycans (CSPGs)) during development physical neuropathy.

Language: Английский

Citations

128