TGF-β1 and TGF-β2 expression after traumatic human spinal cord injury

Buss, A.; Pech, Katrin; Kakulas, Byron; Martin, Didier; Schoenen, Jean; Noth, Johannes; Brook, Gary

doi:10.1038/sj.sc.3102148

Cited by 60 publications

(53 citation statements)

References 22 publications

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“…The present data extends our investigations into the cellular and molecular composition of the lesion site of severe macerating human SCI [31,36,37]. The distribution pattern of individual members of the CSPG family varies significantly after human SCI.…”

Section: Resultssupporting

confidence: 60%

NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury

Buss¹,

Pech²,

Noth³

et al. 2007

Akt Neurol

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Background: A major class of axon growth-repulsive molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs). Experimental spinal cord injury (SCI) has demonstrated rapid reexpression of CSPGs at and around the lesion site. The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery. The potential therapeutic relevance of interfering with CSPG expression or function following experimental injuries seems clear, however, the spatio-temporal pattern of expression of individual members of the CSPG family following human spinal cord injury is only poorly defined. In the present correlative investigation, the expression pattern of CSPG family members NG2, neurocan, versican and phosphacan was studied in the human spinal cord.

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Section: Resultssupporting

confidence: 60%

NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury

Buss¹,

Pech²,

Noth³

et al. 2007

Akt Neurol

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“…Both TGF-beta1 and TGF-beta2 are detectable in macrophages and astrocytes, while TGF-beta1 is also neuron-associated [66] . The cellular localization and temporal expression pattern of TGF-beta after SCi suggest that early induction of TGF-beta1 at the point of SCi modulates acute inflammatory responses and glial scar formation [67] , while the later induction of TGF-beta2 indicates a regulatory role in the maintenance of the scar [68] .…”

Section: Eph/ephrinsmentioning

confidence: 99%

“…After SCi, both vimentin and GFAP are up-regulated in reactive astrocytes [60] . An analysis of mice that are genetically deficient in vimentin or GFAP showed that glial scar , most likely due to the impaired astrocytic motility resulting from the ablation of intermediate filaments [62] .Moreover, the genetic absence of vimentin and GFAP also improves axonal sprouting [63] and facilitates functional recovery in the context of a spinal cord hemisection model [64] .Transforming growth factor-beta TGF-beta expression increases immediately after SCi in the injured segment [65] .Both TGF-beta1 and TGF-beta2 are detectable in macrophages and astrocytes, while TGF-beta1 is also neuron-associated [66] . The cellular localization and temporal expression pattern of TGF-beta after SCi suggest that early induction of TGF-beta1 at the point of SCi modulates acute inflammatory responses and glial scar formation [67] , while the later induction of TGF-beta2 indicates a regulatory role in the maintenance of the scar [68] .…”

mentioning

confidence: 99%

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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“…The temporal pattern of TGFb1 induction and neuronal death suggests that TGF-b1 is predominantly expressed by activated microglia infiltrating the ischemic region (Lehrmann et al 1995). TGF-b1 expression increases following cerebral infarcts and spinal cord injury and mediates microglial activation to control inflammation following injury (Krupinski et al 1996;Brionne et al 2003;Makwana et al 2007;Buss et al 2008). A unique TGF-bdependent population of microglia is present in both mouse and human (Butovsky et al 2014), and treatment with TGF-b1 before or within 2 hours after cerebral ischemia reduces the volume of infarct and neuronal death in several animal models (McNeill et al 1994;Prehn and Krieglstein 1994;Henrich-Noack et al 1996).…”

Section: Injury and Repairmentioning

confidence: 99%