Targeting Microvasculature for Neuroprotection after SCI

Fassbender, Janelle M.; Whittemore, Scott R.; Hagg, Theo

doi:10.1007/s13311-011-0029-1

Cited by 64 publications

(59 citation statements)

References 158 publications

(205 reference statements)

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“…Endothelial cells, basement membranes, pericytes, and astrocytic end-feet processes constitute a specialized system for this functional barrier [5]. Early microvascular reactions and BSCB disruption are instrumental in the pathophysiology of SCI and repair [6,7].…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

Xia

et al. 2016

Neurotherapeutics

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The blood-spinal cord barrier (BSCB) plays important roles in the recovery of spinal cord injury (SCI), and caveolin-1 is essential for the integrity and permeability of barriers. Basic fibroblast growth factor (bFGF) is an important neuroprotective protein and contributes to the survival of neuronal cells. This study was designed to investigate whether bFGF is beneficial for the maintenance of junction proteins and the integrity of the BSCB to identify the relations with caveolin-1 regulation. We examined the integrity of the BSCB with Evans blue dye and fluorescein isothiocyanate-dextran extravasation, measured the junction proteins and matrix metalloproteinases, and evaluated the locomotor function recovery. Our data indicated that bFGF treatment improved the recovery of BSCB and functional locomotion in contusive SCI model rats, reduced the expression and activation of matrix metalloproteinase-9, and increased the expressions of caveolin-1 and junction proteins, including occludin, claudin-5, p120-catenin, and β-catenin. In the brain, in microvascular endothelial cells, bFGF treatment increased the levels of junction proteins, caveolin-1 small interfering RNA abolished the protective effect of bFGF under oxygen-glucose deprivation conditions, and the expression of fibroblast growth factor receptor 1 and co-localization with caveolin-1 decreased significantly, which could not be reversed by bFGF treatment. These findings provide a novel mechanism underlying the beneficial effects of bFGF on the BSCB and recovery of SCI, especially the regulation of caveolin-1.

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Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

Xia

et al. 2016

Neurotherapeutics

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“…Following SCI, the specialized microstructure of the bloodspinal cord barrier is damaged, and the permeability between spinal cord tissue and blood vessels is unrestricted until the subacute phase [110] . Thus, by harnessing this window of barrier impairment, the delivery of pharmacological agents is a feasible approach to treat SCi.…”

Section: Pharmacological Strategiesmentioning

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 lack of local vascular tissue at the injury site hinders the ability of the body to self-heal and limits the use of treatment measures. Reducing blood loss, promoting new blood vessel formation, and restoring blood supply to the lesions may contribute to the recovery of spinal cord injury (Fassbender et al, 2011). One of the primary mechanisms of vascular formation and proliferation involves increased expression of vascular endothelial growth factor (VEGF).…”

Section: Introductionmentioning

confidence: 99%

Influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury

Guo

Wang

et al. 2014

Genet. Mol. Res.

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ABSTRACT.We examined the influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury. Sixty rats with spinal cord injury were divided into an experimental group and a control group and given neural stem cells or an equivalent amount of phosphate-buffered saline by intravenous transplantation, respectively. Basso, Beattie, and Bresnahan (BBB) motor function assessment was performed in rats at different times after transplantation, and von Willebrand factor (vWF) immunofluorescence and Western blot analysis of vascular endothelial growth factor (VEGF) protein were also performed. The BBB scores of rats in the 2 groups were both zero before transplantation. The BBB score gradually increased over time. The BBB score of the experimental group showed no significant difference compared with that of the control group (P > 0.05) 7 days after transplantation. The BBB score of the experimental group was significantly improved compared with that of the control group 14 days after transplantation (P < 0.05). vWF-positive cells and VEGF protein expression in the experimental group were significantly increased compared with those in the control group 7 and 14 days after transplantation, respectively (P < 0.05). Neural stem cell transplantation

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Targeting Microvasculature for Neuroprotection after SCI

Cited by 64 publications

References 158 publications

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

The glial scar in spinal cord injury and repair

Influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury

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