Neuroprotection and immunomodulation by dimethyl fumarate and a heterologous fibrin biopolymer after ventral root avulsion and reimplantation

Kempe, Paula Regina Gelinski; Chiarotto, Gabriela Bortolança; Barraviera, Benedito; Júnior, Rui Seabra Ferreira; Oliveira, Alexandre Leite Rodrigues de

doi:10.1590/1678-9199-jvatitd-2019-0093

Cited by 11 publications

(7 citation statements)

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“…Such findings are in line with studies that used FBP for the same purpose, obtaining favorable results in tissue regeneration [ 12 , 46 ]. The proportion of its components and the sequence of manipulation is adjusted according to the purpose of its use, for example, in the repair of nerve injuries [ 47 ], bone [ 14 , 48 , 49 ], venous ulcers [ 50 , 51 ], and stem cells [ 46 , 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Photobiomodulation Therapy on the Guided Bone Regeneration Process in Defects Filled by Biphasic Calcium Phosphate Associated with Fibrin Biopolymer

et al. 2021

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The aim is to evaluate the effects of photobiomodulation therapy (PBMT) on the guided bone regeneration process (GBR) in defects in the calvaria of rats filled with biphasic calcium phosphate associated with fibrin biopolymer. Thirty male Wistar rats were randomly separated: BMG (n = 10), defects filled with biomaterial and covered by membrane; BFMG (n = 10), biomaterial and fibrin biopolymer covered by membrane; and BFMLG (n = 10), biomaterial and fibrin biopolymer covered by membrane and biostimulated with PBMT. The animals were euthanized at 14 and 42 days postoperatively. Microtomographically, in 42 days, there was more evident bone growth in the BFMLG, limited to the margins of the defect with permanence of the particles. Histomorphologically, an inflammatory infiltrate was observed, which regressed with the formation of mineralized bone tissue. In the quantification of bone tissue, all groups had a progressive increase in new bone tissue with a significant difference in which the BFMLG showed greater bone formation in both periods (10.12 ± 0.67 and 13.85 ± 0.54), followed by BFMG (7.35 ± 0.66 and 9.41 ± 0.84) and BMG (4.51 ± 0.44 and 7.11 ± 0.44). Picrosirius-red staining showed greater birefringence of collagen fibers in yellow-green color in the BFMLG, showing more advanced bone maturation. PBMT showed positive effects capable of improving and accelerating the guided bone regeneration process when associated with biphasic calcium phosphate and fibrin biopolymer.

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Section: Discussionmentioning

confidence: 99%

Photobiomodulation Therapy on the Guided Bone Regeneration Process in Defects Filled by Biphasic Calcium Phosphate Associated with Fibrin Biopolymer

et al. 2021

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“…As showed by immuno uorescence, canine AdMSC in co-localization with the BDNF, GDNF and p75 NTR indicates that the persistence of viable cells into the the microenvironment of lesion was crucial for the neurotrophic factor maintenance released by the cells. Previous studies showed that the use of HFB for reimplantation of ventral nerve roots lesioned or end-to-end nerve cooptation, proved cell support capacity, adhesion for axonal regeneration and neuroprotection [40][41][42][43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we used a scaffold composed of heterologous brin biopolymer (HFB) with adhesive and sealant properties to maintain canine AdMSCs in the local of lesion and to improve their therapeutic potential [38][39][40][41]. Recent studies have shown the ability to this brin to adhere and support the regeneration in the spinal cord and ventral and dorsal roots injuries in experimental models [42][43][44][45][46]. We hypothesized that the multi-functionalization of PCL-NGCs manufactured by 3D printing with canine AdMSCs embedded in brin biopolymer can enhance nerve regeneration following the repair of critical nerve injury in rats.…”

Section: Introductionmentioning

confidence: 99%

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

Rodríguez-Sánchez

Pinto

Cartarozzi

et al. 2020

Preprint

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Background: Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration.Methods: 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL+MSC (NGC multi-functionalized with 106 canine AdMSC embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokines IL-6 and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve.Results: The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL+MSC group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair.Conclusions: 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach, support the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

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“…Dimethyl fumarate (DMF) is a methyl ester synthesized through the esterification of fumaric acid. Recently, DMF has been shown to exert neuroprotective and immunomodulatory effects associated with endogenous antioxidant mechanisms and mitigation of oxidative stress in in vivo models [147,148].…”

Section: Dimethyl Fumaratementioning

confidence: 99%

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

et al. 2022

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Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of rare neurodegenerative inherited disorders. The resulting motor incoordination and progressive functional disabilities lead to reduced lifespan. There is currently no cure for ARCAs, likely attributed to the lack of understanding of the multifaceted roles of antioxidant defense and the underlying mechanisms. This systematic review aims to evaluate the extant literature on the current developments of therapeutic strategies that target oxidative stress for the management of ARCAs. We searched PubMed, Web of Science, and Science Direct Scopus for relevant peer-reviewed articles published from 1 January 2016 onwards. A total of 28 preclinical studies fulfilled the eligibility criteria for inclusion in this systematic review. We first evaluated the altered cellular processes, abnormal signaling cascades, and disrupted protein quality control underlying the pathogenesis of ARCA. We then examined the current potential therapeutic strategies for ARCAs, including aromatic, organic and pharmacological compounds, gene therapy, natural products, and nanotechnology, as well as their associated antioxidant pathways and modes of action. We then discussed their potential as antioxidant therapeutics for ARCAs, with the long-term view toward their possible translation to clinical practice. In conclusion, our current understanding is that these antioxidant therapies show promise in improving or halting the progression of ARCAs. Tailoring the therapies to specific disease stages could greatly facilitate the management of ARCAs.

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Neuroprotection and immunomodulation by dimethyl fumarate and a heterologous fibrin biopolymer after ventral root avulsion and reimplantation

Cited by 11 publications

References 74 publications

Photobiomodulation Therapy on the Guided Bone Regeneration Process in Defects Filled by Biphasic Calcium Phosphate Associated with Fibrin Biopolymer

Photobiomodulation Therapy on the Guided Bone Regeneration Process in Defects Filled by Biphasic Calcium Phosphate Associated with Fibrin Biopolymer

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

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