Basic Fibroblast Growth Factor (bFGF) Enhances Functional Recovery Following Severe Spinal Cord Injury to the Rat

Rabchevsky, Alexander G.; Fugaccia, Isabella; Turner, Ashby; Blades, Deborah A.; Mattson, Mark P.; Scheff, Stephen W.

doi:10.1006/exnr.2000.7399

Cited by 149 publications

(111 citation statements)

References 93 publications

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“…Administration of exogenous growth factors following SCI promotes functional recovery [17,18]; intrathecal administration of bFGF also significantly enhances functional recovery after moderate and severe contusions in SCI rats [19,20], but the precise mechanism underlying the observed therapeutic effects has not been elucidated. In our latest studies, bFGF was demonstrated to inhibit excessive autophagy and endoplasmic reticulum stress in SCI, which contributed to functional recovery [21,22].…”

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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“…For example, the anti-apoptotic Bcl-w (Yan et al, 2000) was not expressed in MK-801-treated injured spinal cords, although it was expressed in sham and injured spinal cords (Table VII). Similarly, bFGF, important to recovery (Rabchevsky et al, 2000), were down-regulated by MK-801. Therefore, DNA microarrays are useful, not only for assessing the potentially beneficial effects of therapeutics, but also for elucidating possible adverse effects.…”

Section: Noninjury-related Effects Of Mk-801 On Spinal Cord Expressiomentioning

confidence: 91%

DNA microarray analysis of the contused spinal cord: Effect of NMDA receptor inhibition

Nešić

Švrakić

et al. 2002

J of Neuroscience Research

102

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Spinal cord injury (SCI)-induced neurodegeneration leads to irreversible and devastating motor and sensory dysfunction. Post-traumatic outcomes are determined by events occurring during the first 24 hours after SCI. An increase in extracellular glutamate concentration to neurotoxic levels is one of the earliest events after SCI. We used Affymetrix DNA oligonucleotide microarrays (with 1,322 DNA probes) analysis to measure gene expression in order to test the hypothesis that SCI-induced N-methyl-D-aspartate (NMDA) receptor activation triggers significant postinjury transcriptional changes. Here we report that SCI, 1 hour after trauma, induced change in mRNA levels of 165 genes and expression sequence tags (ESTs). SCI affected mRNA levels of those genes that regulate predominantly transcription factors, inflammation, cell survival, and membrane excitability. We also report that NMDA receptor inhibition (with -(ϩ)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate ) reversed the effect of SCI on about 50% of the SCI-affected mRNAs. Especially interesting is the finding that NMDA receptor activation participates in the up-regulation of inflammatory factors. Therefore, SCI-induced NMDA receptor activation is one of the dominant, early signals after trauma that leads to changes in mRNA levels of a number of genes relevant to recovery processes. The majority of MK-801 effects on the SCI-induced mRNA changes reported here are novel. Additionally, we found that the MK-801 treatment also changed the mRNA levels of 168 genes and ESTs that had not been affected by SCI alone, and that some of their gene products could have harmful effects on SCI outcome.

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“…For example, bFGF is induced in injured brain regions (mainly in astrocytes) after trauma and in disease pathology such as Alzheimer's where astrogliosis is very active (Gomez-Pinilla, et al, 1990). After spinal cord injury, bFGF is upregulated in the spinal cord, which promotes functional recovery (Koshinaga et al, 1993;Lee et al, 1999;Rabchevsky et al, 2000). bFGF is also upregulated in the spinal cord after sciatic cryoneurolysis but not after chronic constriction injury , which indicates that upregulation might be associated with the severity of the injury.…”

Section: Activation Of the Jnk Cascade In Spinal Astrocytes And Neuromentioning

confidence: 99%

Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathway

et al. 2006

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Although pain is regarded traditionally as neuronally mediated, recent progress shows an important role of spinal glial cells in persistent pain sensitization. Mounting evidence has implicated spinal microglia in the development of chronic pain (e.g. neuropathic pain after peripheral nerve injury). Less is known about the role of astrocytes in pain regulation. However, astrocytes have very close contact with synapses and maintain homeostasis in the extracellular environment. In this review, we provide evidence to support a role of spinal astrocytes in maintaining chronic pain. In particular, cJun N-terminal kinase (JNK) is activated persistently in spinal astrocytes in a neuropathic pain condition produced by spinal nerve ligation. This activation is required for the maintenance of neuropathic pain because spinal infusion of JNK inhibitors can reverse mechanical allodynia, a major symptom of neuropathic pain. Further study reveals that JNK is activated strongly in astrocytes by basic fibroblast growth factor (bFGF), an astroglial activator. Intrathecal infusion of bFGF also produces persistent mechanical allodynia. After peripheral nerve injury, bFGF might be produced by primary sensory neurons and spinal astrocytes because nerve injury produces robust bFGF upregulation in both cell types. Therefore, the bFGF/JNK pathway is an important signalling pathway in spinal astrocytes for chronic pain sensitization. Investigation of signaling mechanisms in spinal astrocytes will identify new molecular targets for the management of chronic pain.

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Basic Fibroblast Growth Factor (bFGF) Enhances Functional Recovery Following Severe Spinal Cord Injury to the Rat

Cited by 149 publications

References 93 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

DNA microarray analysis of the contused spinal cord: Effect of NMDA receptor inhibition

Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathway

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