Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury

Dias, David O.; Kim, Hoseok; Holl, Daniel; Solnestam, Beata Werne; Lundeberg, Joakim; Carlén, Marie; Göritz, Christian; Frisén, Jonas

doi:10.1016/j.cell.2018.02.004

Cited by 297 publications

(350 citation statements)

References 65 publications

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“…Determining the origin of scar‐forming cells could be of great clinical interest. Accordingly, reducing pericyte‐derived fibrotic scar tissue promotes functional recovery after spinal cord injury (Dias et al, ).…”

Section: Discussionmentioning

confidence: 99%

Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

Roth

Enström

Aghabeick

et al. 2019

J of Neuroscience Research

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Scar formation after injury of the brain or spinal cord is a common event. While glial scar formation by astrocytes has been extensively studied, much less is known about the fibrotic scar, in particular after stroke. Platelet‐derived growth factor receptor ß‐expressing (PDGFRß+) pericytes have been suggested as a source of the fibrotic scar depositing fibrous extracellular matrix (ECM) proteins after detaching from the vessel wall. However, to what extent these parenchymal PDGFRß+ cells contribute to the fibrotic scar and whether targeting these cells affects fibrotic scar formation in stroke is still unclear. Here, we utilize male transgenic mice that after a permanent middle cerebral artery occlusion stroke model have a shift from a parenchymal to a perivascular location of PDGFRß+ cells due to the loss of regulator of G‐protein signaling 5 in pericytes. We find that only a small fraction of parenchymal PDGFRß+ cells co‐label with type I collagen and fibronectin. Consequently, a reduction in parenchymal PDGFRß+ cells by ca. 50% did not affect the overall type I collagen or fibronectin deposition after stroke. The redistribution of PDGFRß+ cells to a perivascular location, however, resulted in a reduced thickening of the vascular basement membrane and changed the temporal dynamics of glial scar maturation after stroke. We demonstrate that parenchymal PDGFRß+ cells are not the main contributor to the fibrotic ECM, and therefore targeting these cells might not impact on fibrotic scar formation after stroke.

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Section: Discussionmentioning

confidence: 99%

Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

Roth

Enström

Aghabeick

et al. 2019

J of Neuroscience Research

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“…Pericytes have been implicated in scar formation in the brain following cerebral ischemia. The stromal cells have a similar marker profile as cells involved in scar formation in the spinal cord, which also are proposed to be pericytederived [154,155]. The stromal cells have a similar marker profile as cells involved in scar formation in the spinal cord, which also are proposed to be pericytederived [154,155].…”

Section: Cerebrovascular Diseases Affecting the Cnsmentioning

confidence: 92%

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

2019

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Neurodegenerative and cerebrovascular diseases cause considerable human suffering, and therapy options for these two disease categories are limited or non-existing. It is an emerging notion that neurodegenerative and cerebrovascular diseases are linked in several ways, and in this review, we discuss the current status regarding vascular dysregulation in neurodegenerative disease, and conversely, how cerebrovascular diseases are associated with central nervous system (CNS) degeneration and dysfunction. The emerging links between neurodegenerative and cerebrovascular diseases are reviewed with a particular focus on pericytes-important cells that ensheath the endothelium in the microvasculature and which are pivotal for blood-brain barrier function and cerebral blood flow. Finally, we address how novel molecular and cellular insights into pericytes and other vascular cell types may open new avenues for diagnosis and therapy development for these important diseases.

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“…Likewise, current conditional and inducible Cre lines (e.g., PDGFRα CreERT and NG2 CreERT) used to manipulate gene expression in OPCs share expression of these genes with vasculature‐associated cells including pericytes (Assinck, Duncan, Plemel, et al, ; Kang et al, ). Pericytes contribute to the accumulation of fibrotic stromal cells within the scar, which inhibits corticospinal axon growth (Dias et al, ). Caution is therefore necessary when interpreting these studies as an OPC‐specific effect.…”

Section: Introductionmentioning

confidence: 99%

The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury

Duncan

Manesh

Hilton

et al. 2019

Glia

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Oligodendrocyte progenitor cells (OPCs) are the most proliferative and dispersed population of progenitor cells in the adult central nervous system, which allows these cells to rapidly respond to damage. Oligodendrocytes and myelin are lost after traumatic spinal cord injury (SCI), compromising efficient conduction and, potentially, the long‐term health of axons. In response, OPCs proliferate and then differentiate into new oligodendrocytes and Schwann cells to remyelinate axons. This culminates in highly efficient remyelination following experimental SCI in which nearly all intact demyelinated axons are remyelinated in rodent models. However, myelin regeneration comprises only one role of OPCs following SCI. OPCs contribute to scar formation after SCI and restrict the regeneration of injured axons. Moreover, OPCs alter their gene expression following demyelination, express cytokines and perpetuate the immune response. Here, we review the functional contribution of myelin regeneration and other recently uncovered roles of OPCs and their progeny to repair following SCI.

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Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury

Cited by 297 publications

References 65 publications

Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury

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