Neuronal Redevelopment and the Regeneration of Neuromodulatory Axons in the Adult Mammalian Central Nervous System DOI Creative Commons

Patrick Cooke,

Haley N. Janowitz,

Sarah Dougherty

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: April 22, 2022

One reason that many central nervous system injuries, including those arising from traumatic brain injury, spinal cord and stroke, have limited recovery of function is neurons within the adult mammalian CNS lack ability to regenerate their axons following trauma. This stands in contrast peripheral (PNS). New evidence, provided by single-cell expression profiling, suggests that, both can revert an embryonic-like growth state which permissive for axon regeneration. "redevelopment" strategy could facilitate a damage response necessary isolate repair acute injury provide intracellular machinery regrowth. Interestingly, serotonin rostral group raphe nuclei, project into forebrain, display robust unaided, counter widely held view cannot without experimental intervention after injury. Furthermore, initial evidence norepinephrine locus coeruleus possess similar regenerative abilities. Several morphological characteristics regeneration mammals, observable using longitudinal vivo imaging, are distinct known unaided nerve regeneration, or seen optic occurs with intervention. These results suggest there alternative program likely differs displayed PNS.

Language: Английский

The Biology of Regeneration Failure and Success After Spinal Cord Injury DOI Open Access
Amanda Tran, Philippa M. Warren, Jerry Silver

et al.

Physiological Reviews, Journal Year: 2018, Volume and Issue: 98(2), P. 881 - 917

Published: March 7, 2018

Since no approved therapies to restore mobility and sensation following spinal cord injury (SCI) currently exist, a better understanding of the cellular molecular mechanisms SCI that compromise regeneration or neuroplasticity is needed develop new strategies promote axonal regrowth function. Physical trauma results in vascular disruption that, turn, causes blood-spinal barrier rupture leading hemorrhage ischemia, followed by rampant local cell death. As subsequent edema inflammation occur, neuronal glial necrosis apoptosis spread well beyond initial site impact, ultimately resolving into cavity surrounded glial/fibrotic scarring. The scar, which stabilizes secondary injury, also acts as chronic, physical, chemo-entrapping prevents regeneration. Understanding formative events scarring helps guide towards development potential enhance axon functional recovery at both acute chronic stages SCI. This review will discuss perineuronal net how chondroitin sulfate proteoglycans (CSPGs) deposited scar impede outgrowth level growth cone. We end with summary current CSPG-targeting help foster regeneration, neuroplasticity/sprouting,

Language: Английский

Citations

701
Microglia-organized scar-free spinal cord repair in neonatal mice DOI
Yi Li, Xuelian He, Riki Kawaguchi

et al.

Nature, Journal Year: 2020, Volume and Issue: 587(7835), P. 613 - 618

Published: Oct. 7, 2020

Language: Английский

Citations

317
Dissecting spinal cord regeneration DOI
Michael V. Sofroniew

Nature, Journal Year: 2018, Volume and Issue: 557(7705), P. 343 - 350

Published: May 8, 2018

Language: Английский

Citations

296
The translational landscape in spinal cord injury: focus on neuroplasticity and regeneration DOI
Thomas H. Hutson, Simone Di Giovanni

Nature Reviews Neurology, Journal Year: 2019, Volume and Issue: 15(12), P. 732 - 745

Published: Nov. 14, 2019

Language: Английский

Citations

262
Touch and tactile neuropathic pain sensitivity are set by corticospinal projections DOI
Yuanyuan Liu, Alban Latrémolière, Xinjian Li

et al.

Nature, Journal Year: 2018, Volume and Issue: 561(7724), P. 547 - 550

Published: Sept. 1, 2018

Language: Английский

Citations

236
Reactivation of Dormant Relay Pathways in Injured Spinal Cord by KCC2 Manipulations DOI Creative Commons
Bo Chen, Yi Li, Bin Yu

et al.

Cell, Journal Year: 2018, Volume and Issue: 174(3), P. 521 - 535.e13

Published: July 1, 2018

Language: Английский

Citations

220
Injured adult neurons regress to an embryonic transcriptional growth state DOI
Gunnar Poplawski, Riki Kawaguchi,

Erna van Niekerk

et al.

Nature, Journal Year: 2020, Volume and Issue: 581(7806), P. 77 - 82

Published: April 15, 2020

Language: Английский

Citations

212
Axon Regeneration in the Central Nervous System: Facing the Challenges from the Inside DOI

Michele Curcio,

Frank Bradke

Annual Review of Cell and Developmental Biology, Journal Year: 2018, Volume and Issue: 34(1), P. 495 - 521

Published: July 25, 2018

After an injury in the adult mammalian central nervous system (CNS), lesioned axons fail to regenerate. This failure regenerate contrasts with axons' remarkable potential grow during embryonic development and after peripheral (PNS). Several intracellular mechanisms-including cytoskeletal dynamics, axonal transport trafficking, signaling transcription of regenerative programs, epigenetic modifications-control axon regeneration. In this review, we describe how manipulation intrinsic mechanisms elicits a response different organisms strategies are implemented form basis future treatment CNS injury.

Language: Английский

Citations

191
Microglia coordinate cellular interactions during spinal cord repair in mice DOI Creative Commons
Faith H. Brennan, Yang Li, Cankun Wang

et al.

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

Citations

165
A spinal microglia population involved in remitting and relapsing neuropathic pain DOI
Keita Kohno, Ryoji Shirasaka,

Kohei Yoshihara

et al.

Science, Journal Year: 2022, Volume and Issue: 376(6588), P. 86 - 90

Published: March 31, 2022

Neuropathic pain is often caused by injury and diseases that affect the somatosensory system. Although development has been well studied, recovery mechanisms remain largely unknown. Here, we found CD11c-expressing spinal microglia appear after of behavioral hypersensitivity following nerve injury. Nerve-injured mice with CD11c+ microglial depletion failed to recover spontaneously from this hypersensitivity. expressed insulin-like growth factor-1 (IGF1), interference IGF1 signaling recapitulated impairment in recovery. In pain-recovered mice, or interruption resulted a relapse Our findings reveal mechanism for remission recurrence neuropathic pain, providing potential targets therapeutic strategies.

Language: Английский

Citations

163