EphA4 deficient mice maintain astroglial–fibrotic scar formation after spinal cord injury

Herrmann, Julia; Shah, Riddhi; Chan, Andrea F.; Zheng, Binhai

doi:10.1016/j.expneurol.2010.02.005

Cited by 44 publications

(38 citation statements)

References 55 publications

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“…7A). The up-regulation of GFAP at the injury site is similar to that observed in other models of spinal cord injury (Herrmann et al, 2010;Sofroniew, 2009).…”

Section: Tissue Loss In the Spinal Cord Is Proportional To The Degreesupporting

confidence: 85%

Characterization of a novel bidirectional distraction spinal cord injury animal model

Seifert

Bell

Elmer

et al. 2011

Journal of Neuroscience Methods

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“…7A). The up-regulation of GFAP at the injury site is similar to that observed in other models of spinal cord injury (Herrmann et al, 2010;Sofroniew, 2009).…”

Section: Tissue Loss In the Spinal Cord Is Proportional To The Degreesupporting

confidence: 85%

Characterization of a novel bidirectional distraction spinal cord injury animal model

Seifert

Bell

Elmer

et al. 2011

Journal of Neuroscience Methods

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“…Members of this family are up-regulated following CNS injury (18,19). EphA4 has been implicated in the response to injury both as an astrocyte and as a neuronally expressed protein, but its functional role in recovery from neuronal injury is not clear (20)(21)(22)(23). Macrophage EphB3 has also been implicated in adult axon regeneration (24).…”

Section: Neurology | Locomotionmentioning

confidence: 99%

Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury

Duffy

Wang

Siegel

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Recovery of neurological function after traumatic injury of the adult mammalian central nervous system is limited by lack of axonal growth. Myelin-derived inhibitors contribute to axonal growth restriction, with ephrinB3 being a developmentally important axonal guidance cue whose expression in mature oligodendrocytes suggests a role in regeneration. Here we explored the in vivo regeneration role of ephrinB3 using mice lacking a functional ephrinB3 gene. We confirm that ephrinB3 accounts for a substantial portion of detergent-resistant myelin-derived inhibition in vitro. To assess in vivo regeneration, we crushed the optic nerve and examined retinal ganglion fibers extending past the crush site. Significantly increased axonal regeneration is detected in ephrinB3 −/− mice. Studies of spinal cord injury in ephrinB3 −/− mice must take into account altered spinal cord development and an abnormal hopping gait before injury. In a near-total thoracic transection model, ephrinB3 −/− mice show greater spasticity than wild-type mice for 2 mo, with slightly greater hindlimb function at later time points, but no evidence for axonal regeneration. After a dorsal hemisection injury, increased corticospinal and raphespinal growth in the caudal spinal cord are detected by 6 wk. This increased axonal growth is accompanied by improved locomotor performance measured in the open field and by kinematic analysis. Thus, ephrinB3 contributes to myelin-derived axonal growth inhibition and limits recovery from adult CNS trauma.

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“…Notably, a study by Turnley's team showed that astrocytic gliosis and glial scars are greatly reduced in EphA4-deficient mice after a lateral spinal cord hemisection [57] . in contrast, the genetic deletion of EphA4 does not significantly alter the astroglial response or cause the development of an astroglial fibrotic scar after dorsal hemisection SCi in mice [58] . This discrepancy cannot be simply explained by the lesion models used.…”

Section: Eph/ephrinsmentioning

confidence: 78%

The glial scar in spinal cord injury and repair

2013

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Glial scarring following severe tissue damage and inflammation after spinal cord injury (SCi) is due to an extreme, uncontrolled form of reactive astrogliosis that typically occurs around the injury site. The scarring process includes the misalignment of activated astrocytes and the deposition of inhibitory chondroitin sulfate proteoglycans. Here, we first discuss recent developments in the molecular and cellular features of glial scar formation, with special focus on the potential cellular origin of scar-forming cells and the molecular mechanisms underlying glial scar formation after SCi. Second, we discuss the role of glial scar formation in the regulation of axonal regeneration and the cascades of neuro-inflammation. Last, we summarize the physical and pharmacological approaches targeting the modulation of glial scarring to better understand the role of glial scar formation in the repair of SCi.Keywords: glial scar; spinal cord injury; axonal regeneration; astrocyte activation; reactive astrogliosis; neuroinflammation IntroductionSpinal cord injury (SCi) is a common and devastating central nervous system (CNS) insult that results in disruption of cord microstructure and is followed by limited neuronal regeneration and insufficient functional recovery in adult mammals. After severe SCi, and in response to changes in the local microenvironment, astrocytes, the most abundant glial cells in the CNS, transform into reactive astrocytes and undergo dramatic morphological changes [1] as well as massive variations in gene expression [2] . Reactive astrocytes, the major component of glial scars, along with other cells in the spinal cord and blood-borne cells leaking from the damaged blood-spinal cord barrier, participate in the process of scar formation [3] .From the historical perspective, a glial scar is recognized as an impediment to the regeneration of axons in the cord because of the irregular rearrangement of hypertrophic astrocytic processes, as well as major components of the axonal inhibitory extracellular matrix (ECM), including chondroitin sulfate proteoglycans (CSPGs) that are secreted by the reactive astrocytes [4] . Currently, increasing evidence is advancing our knowledge of the mechanism of the formation of glial scars after a lesion and the roles of glial scars in the regulation of neuro-inflammation and repair processes [5,6] .This article reviews the following: (1) the molecular and cellular properties of glial scar formation following SCi;(2) the roles of glial scar formation in axonal regeneration and neuro-inflammation; and (3) the current status of scarmodulating therapeutic strategies for spinal cord repair after injury. Molecular and Cellular Properties of Glial Scars Characterization of Glial ScarsTraumatic damage of the spinal cord can result in seallike scar tissue in the lesion zone, which is filled with dense cellular components and a connective matrix. Generally, the scar tissue is classified into two parts, fibrotic and glial. 422The fibrotic scar, primarily composed of invading fibrobl...

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EphA4 deficient mice maintain astroglial–fibrotic scar formation after spinal cord injury

Cited by 44 publications

References 55 publications

Characterization of a novel bidirectional distraction spinal cord injury animal model

Characterization of a novel bidirectional distraction spinal cord injury animal model

Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury

The glial scar in spinal cord injury and repair

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