Astrocyte scar formation aids central nervous system axon regeneration

Nature, Journal Year: 2016, Volume and Issue: 532(7598), P. 195 - 200

Published: March 29, 2016

Language: Английский

---

The Biology of Regeneration Failure and Success After Spinal Cord Injury

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

---

Building the Neuronal Microtubule Cytoskeleton

Neuron, Journal Year: 2015, Volume and Issue: 87(3), P. 492 - 506

Published: Aug. 1, 2015

Language: Английский

---

Intrinsic Control of Axon Regeneration

Neuron, Journal Year: 2016, Volume and Issue: 90(3), P. 437 - 451

Published: May 1, 2016

Language: Английский

---

Moving beyond the glial scar for spinal cord repair

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Aug. 28, 2019

Abstract Traumatic spinal cord injury results in severe and irreversible loss of function. The triggers a complex cascade inflammatory pathological processes, culminating formation scar. While traditionally referred to as glial scar, the scar fact comprises multiple cellular extracellular components. This multidimensional nature should be considered when aiming understand role scarring limiting tissue repair recovery. In this Review we discuss recent advances understanding composition phenotypic characteristics oversimplification defining binary terms good or bad, development therapeutic approaches target components enable improved functional outcome after injury.

Language: Английский

---

Cell biology of spinal cord injury and repair

Journal of Clinical Investigation, Journal Year: 2017, Volume and Issue: 127(9), P. 3259 - 3270

Published: July 23, 2017

Spinal cord injury (SCI) lesions present diverse challenges for repair strategies. Anatomically complete injuries require restoration of neural connectivity across lesions. incomplete may benefit from augmentation spontaneous circuit reorganization. Here, we review SCI cell biology, which varies considerably three different lesion-related tissue compartments: (a) non-neural lesion core, (b) astrocyte scar border, and (c) surrounding spared but reactive tissue. After SCI, axon growth reorganization are determined by neuron-cell-autonomous mechanisms interactions among neurons, glia, immune other cells. These shaped both the presence absence growth-modulating molecules, vary markedly in compartments. The emerging understanding how biology differs compartments is fundamental to developing rationally targeted

Language: Английский

---

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

Neurotherapeutics, Journal Year: 2018, Volume and Issue: 15(3), P. 541 - 553

Published: May 1, 2018

Language: Английский

---

Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury

Cell, Journal Year: 2018, Volume and Issue: 173(1), P. 153 - 165.e22

Published: March 1, 2018

CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report inhibiting generation of progeny by a subclass pericytes led decreased fibrosis and extracellular matrix deposition after spinal cord mice. Regeneration raphespinal corticospinal tract axons was enhanced sensorimotor function recovery improved following animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate regenerated integrated into local circuitry below site. The number correlated recovery. In conclusion, attenuation represents promising therapeutic approach facilitate injury.

Language: Английский

---

Central Nervous System Regenerative Failure: Role of Oligodendrocytes, Astrocytes, and Microglia

Cold Spring Harbor Perspectives in Biology, Journal Year: 2014, Volume and Issue: 7(3), P. a020602 - a020602

Published: Dec. 4, 2014

Jerry Silver1, Martin E. Schwab2 and Phillip G. Popovich3 1Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44140 2Brain Research Institute, University Zurich Department Health Sciences Technology, ETH Zurich, 8057 Switzerland 3Center for Brain Spinal Cord Repair, State Columbus, 43210 Correspondence: phillip.popovich{at}osumc.edu

Language: Английский

---

Axonal transport: Driving synaptic function

Science, Journal Year: 2019, Volume and Issue: 366(6462)

Published: Oct. 11, 2019

From trafficking to maintenance Neurons are remarkably polarized in that proteins made the cytosol often need travel many tens or hundreds of cell body lengths along axons their sites action synapse. Axonal transport these components is driven by molecular motors axonal microtubules. Guedes-Dias and Holzbaur review biology highlight roles this fundamental process plays organismal health. Science , issue p. eaaw9997

Language: Английский

---