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Application of neurotrophic and proangiogenic factors as therapy after peripheral nervous system injury

Neural Regeneration Research 2022年第6期17卷 1240-1247页

作者： Kamilla Faritovna Idrisova Alina Kazymovna Zeinalova Galina Andreevna masgutova Alexey Andreevich Bogov Jr. Cinzia Allegrucci Valeriia Yurievna Syromiatnikova Ilnur Ildusovich Salafutdinov Ekaterna Evgenievna Garanina Dina Ivanovna Andreeva Adilet Abdullaatovich Kadyrov Albert Anatolevich Rizvanov ruslan faridovich masgutov Institute of Fundamental Medicine and Biology Kazan Federal UniversityKazanRussia Republican Clinical Hospital KazanRussia Biodiscovery Institute School of Veterinary Medicine and ScienceUniversity of NottinghamNottinghamUK Department of Traumatology and Orthopedics Kazan State Medical AcademyKazanRussia

The intrinsic ability of peripheral nerves to regenerate after injury is extremely limited,especially in case of severe injury.This often leads to poor motor function and permanent disability.Existing approaches for the treatment of injured nerves do not provide appropriate conditions to support survival and growth of nerve cells.This drawback can be compensated by the use of gene therapy and cell therapy-based drugs that locally provide an increase in the key regulators of nerve growth,including neurotrophic factors and extracellular matrix proteins.Each growth factor plays its own specific angiotrophic or neurotrophic role.Currently,growth factors are widely studied as accelerators of nerve regeneration.Particularly noteworthy is synergy between various growth factors,that is essential for both angiogenesis and neurogenesis.Fibroblast growth factor 2 and vascular endothelial growth factor are widely known for their proangiogenic effects.At the same time,fibroblast growth factor 2 and vascular endothelial growth factor stimulate neural cell growth and play an important role in neurodegenerative diseases of the peripheral nervous system.Taken together,their neurotrophic and angiogenic properties have positive effect on the regeneration process.In this review we provide an in-depth overview of the role of fibroblast growth factor 2 and vascular endothelial growth factor in the regeneration of peripheral nerves,thus demonstrating their neurotherapeutic efficacy in improving neuron survival in the peripheral nervous system.

关键词： fibroblast growth factor 2 growth factors nerve growth factor peripheral nerve injury peripheral nervous system vascular endothelial growth factor

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Angiogenesis and nerve regeneration induced by local administration of plasmid pBud-coVEGF165-coFGF2 into the intact rat sciatic nerve

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Neural Regeneration Research 2021年第9期16卷 1882-1889页

作者： ruslan masgutov Alina Zeinalova Alexey Bogov Galina masgutova Ilnur Salafutdinov Ekaterina Garanina Valeriia Syromiatnikova Kamilla Idrisova Adelya Mullakhmetova Dina Andreeva Liliya Mukhametova Adilet Kadyrov Igor Pankov Albert Rizvanov OpenLab“Gene and Cell Technologies” Institute of Fundamental Medicine and BiologyKazan Federal UniversityKazanRussia Republican Clinical Hospital KazanRussia Department of Traumatology and Orthopedics Kazan State Medical AcademyKazanRussia

Vascular endothelial growth factor(VEGF) and fibroblast growth factor 2(FGF2) are well-known growth factors involved in the regeneration of various tissues and organs, including peripheral nerve system. In the present study, we elucidated the local and systemic effects of plasmid construct рBud-coVEGF165-coFGF2 injected into the epineurium of intact rat sciatic nerve. Results of histological examination of sciatic nerve and multiplex immunoassays of serum showed the absence of immunogenicity and biosafety of plasmid рBud-coVEGF165-coFGF2. Moreover, local administration of plasmid DNA construct resulted in significantly decreased levels of pro-inflammatory cytokines in the peripheral blood, including tumor necrosis factor α(TNFα) and interleukin-12, and significantly increased levels of cytokines and chemokines including Regulated upon Activation, Normal T Cell Expressed and Presumably Secrete(RANTES), epidermal growth factor, interleukin-2, and monocyte chemoattractant protein 1. These changes in the peripheral blood on day 7 after injection of plasmid construct рBud-coVEGF165-coFGF2 show that the plasmid construct has systemic effects and may modulate immune response. At the same time, reverse transcriptionpolymerase chain reaction revealed transient expression of coFGF2, coVEGF165, ratFGF2 and ratVEGFA with direct transport of transcripts from distal part to proximal part of the sciatic nerve. Immunohistochemical staining revealed prolonged presence of VEGFA in sciatic nerve till 14 days post-injection. These findings suggest that local administration of plasmid construct рBud-coVEGF165-coFGF2 at a concentration of 30 ng/μL results in the formation of pro-angiogenic stimuli and, and the plasmid construct, used as a drug for gene therapy, might potentially facilitate regeneration of the sciatic nerve. The study was approved by the Animal Ethics Committee of Kazan Federal University, procedures were approved by the Local Ethics Committee(approval No. 5) on May 27, 2014.

关键词： chemokines cytokines fibroblast growth factor gene therapy growth factors peripheral nerve system sciatic nerve regeneration vascular endothelial growth factor

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