LOTUS overexpression via ex vivo gene transduction further promotes recovery of motor function following human iPSC-NS/PC transplantation for contusive spinal cord injury

Spinal cord injury results in a wide range of behavioral changes including impaired motor and sensory function, autonomic dysfunction, spasticity, and depression. Currently, restoring lost motor function is the most actively studied and sought-after goal of spinal cord injury research. This research is rooted in the fact that although self-repair following spinal cord injury in adult mammals is very limited, there can be some recovery of motor function. This recovery is strongly dependent on the lesion size and location as well as on neural activity of denervated networks activated mainly through physical activity (i.e., rehabilitative training). Recovery of motor function is largely due to neuroplasticity, which includes adaptive changes in spared and injured neural circuitry. Neuroplasticity after spinal cord injury is extensive and includes mechanisms such as moderate axonal sprouting, the formation of new synaptic connections, network remapping, and changes to neuron cell properties. Neuroplasticity after spinal cord injury has been described at various physiological and anatomical levels of the central nervous system including the brain, brainstem, and spinal cord, both above and below injury sites. The growing number of mechanisms underlying postinjury plasticity indicate the vast complexity of injury-induced plasticity. This poses important opportunities to further enhance and harness plasticity in order to promote recovery. However, the diversity of neuroplasticity also creates challenges for research, which is frequently based on mechanistically driven approaches. The appreciation of the complexity of neuronal plasticity and the findings that recovery is based on a multitude and interlinked adaptations will be essential in developing meaningful new treatment avenues.

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Effect of vitamins C and E on recovery of motor function after spinal cord injury: systematic review and meta-analysis of animal studies

Nutrition Reviews ◽

10.1093/nutrit/nuz076 ◽

2019 ◽

Vol 78 (6) ◽

pp. 465-473 ◽

Cited By ~ 1

Author(s):

Mostafa Hosseini ◽

Arash Sarveazad ◽

Asrin Babahajian ◽

Masoud Baikpour ◽

Alexander R Vaccaro ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Vitamin E ◽

Animal Models ◽

Vitamin C ◽

Motor Function ◽

Animal Studies ◽

Meta Analysis ◽

Cord Injury ◽

Recovery Of Motor Function

Abstract Context Many animal studies have evaluated the role of vitamins in the recovery of motor function after spinal cord injury, but their results have been contradictory and no consensus has been reached. Objective This meta-analysis aimed to investigate the effects of vitamin C and vitamin E on recovery of motor function after spinal cord injury in animal models. Data Sources Two authors independently collected the records of relevant articles published in MEDLINE, Embase, Scopus, and Web of Science through November 2018. Study Selection All studies conducted in animal models to evaluate the therapeutic effects of vitamin C or vitamin E or both on recovery of motor function after spinal cord injury were included. Studies that lacked a control group or a standard treatment, lacked an assessment of motor function, included genetically modified/engineered animals, included animals pretreated with vitamin C or vitamin E, or combined vitamin treatment with other methods, such as cell therapies, were excluded. Data Extraction Data from 10 articles met the inclusion criteria for meta-analysis, conducted in accordance with PRISMA guidelines. Results Daily supplementation with vitamin C (P < 0.0001) and vitamin E (P < 0.0001) significantly improved the recovery of motor function in animals affected by spinal cord injury. Vitamin C supplementation is effective only when administered intraperitoneally (P < 0.0001). Concurrent supplementation with both vitamins does not show better efficacy than treatment with either one alone. Conclusion Administration of vitamin C and vitamin E in animal models of spinal cord injury significantly improves the recovery of motor function.

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The Extract of Roots of Sophora flavescens Enhances the Recovery of Motor Function by Axonal Growth in Mice with a Spinal Cord Injury

Frontiers in Pharmacology ◽

10.3389/fphar.2015.00326 ◽

2016 ◽

Vol 6 ◽

Cited By ~ 7

Author(s):

Norio Tanabe ◽

Tomoharu Kuboyama ◽

Kohei Kazuma ◽

Katsuhiro Konno ◽

Chihiro Tohda

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Function ◽

Axonal Growth ◽

Sophora Flavescens ◽

Cord Injury ◽

Recovery Of Motor Function

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Recovery of Motor Function Following Spinal Cord Injury

10.5772/61539 ◽

2016 ◽

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Function ◽

Cord Injury ◽

Recovery Of Motor Function

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Post–spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG

Journal of Neurosurgery Spine ◽

10.3171/2016.9.spine15959 ◽

2017 ◽

Vol 27 (1) ◽

pp. 105-115 ◽

Cited By ~ 10

Author(s):

Tatyana Povysheva ◽

Maksim Shmarov ◽

Denis Logunov ◽

Boris Naroditsky ◽

Ilya Shulman ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Function ◽

Fold Increase ◽

Adenoviral Vectors ◽

Control Group ◽

Cord Injury ◽

Lateral Sclerosis ◽

Recovery Of Motor Function ◽

Intraspinal Injection

OBJECTIVEThe most actively explored therapeutic strategy for overcoming spinal cord injury (SCI) is the delivery of genes encoding molecules that stimulate regeneration. In a mouse model of amyotrophic lateral sclerosis and in preliminary clinical trials in patients with amyotrophic lateral sclerosis, the combined administration of recombinant adenoviral vectors (Ad5-VEGF+Ad5-ANG) encoding the neurotrophic/angiogenic factors vascular endothelial growth factor (VEGF) and angiogenin (ANG) was found to slow the development of neurological deficits. These results suggest that there may be positive effects of this combination of genes in posttraumatic spinal cord regeneration. The objective of the present study was to determine the effects of Ad5-VEGF+Ad5-ANG combination therapy on motor function recovery and reactivity of astrocytes in a rat model of SCI.METHODSSpinal cord injury was induced in adult Wistar rats by the weight-drop method. Rats (n = 51) were divided into 2 groups: the experimental group (Ad5-VEGF+Ad5-ANG) and the control group (Ad5-GFP [green fluorescent protein]). Recovery of motor function was assessed using the Basso, Beattie, and Bresnahan scale. The duration and intensity of infectivity and gene expression from the injected vectors were assessed by immunofluorescent detection of GFP. Reactivity of glial cells was assessed by changes in the number of immunopositive cells expressing glial fibrillary acidic protein (GFAP), S100β, aquaporin 4 (AQP4), oligodendrocyte transcription factor 2, and chondroitin sulfate proteoglycan 4. The level of S100β mRNA expression in the spinal cord was estimated by real-time polymerase chain reaction.RESULTSPartial recovery of motor function was observed 30 days after surgery in both groups. However, Basso, Beattie, and Bresnahan scores were 35.9% higher in the Ad5-VEGF+Ad5-ANG group compared with the control group. Specific GFP signal was observed at distances of up to 5 mm in the rostral and caudal directions from the points of injection. A 1.5 to 2.0–fold increase in the number of GFAP+, S100β+, and AQP4+ cells was observed in the white and gray matter at a distance of up to 5 mm from the center of the lesion site in the caudal and rostral directions. At 30 days after injury, a 2-fold increase in S100β transcripts was observed in the Ad5-VEGF+Ad5-ANG group compared with the control group.CONCLUSIONSIntraspinal injection of recombinant adenoviral vectors encoding VEGF and ANG stimulates functional recovery after traumatic SCI. The increased number of S100β+ astrocytes induced by this approach may be a beneficial factor for maintaining the survival and function of neurons. Therefore, gene therapy with Ad5-VEGF+Ad5-ANG vectors is an effective therapeutic method for SCI treatment.

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Curcumin Promotes Recovery of Motor Function After Spinal Cord Injury in Rats Through Mammalian Target of Rapamycin (mTOR)-Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2287 ◽

2020 ◽

Vol 10 (4) ◽

pp. 562-568

Author(s):

Xianfeng Jiang ◽

Fengwu Tang ◽

Guang Han ◽

Chen Yun ◽

Xuyi Chen ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Signaling Pathway ◽

Motor Function ◽

Mammalian Target Of Rapamycin ◽

Target Of Rapamycin ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway ◽

Cord Injury ◽

Recovery Of Motor Function

Objective: Curcumin possesses extensive therapeutic effects on several diseases and tumor cells, which has inhibitory effects on mammalian target of rapamycin (mTOR)-STAT3 signaling. Our study aims to explore the influences of curcumin on promoting the recovery of motor function after spinal cord injury (SCI) in rats through the mTOR-STAT3 signaling pathway. Methods : SCI rats were treated with rapamycin and curcumin followed by establishing rat models of SCI. The influences of rapamycin and curcumin on the protein expressions of PTEN, Akt, phosphorylated S6 and chondroitin sulphate proteoglycans (CSPGs) were measured by western blot. Means of Basso, Beattie and Bresnahan (BBB) locomotor rating scale was used to assess motor function. Results: After SCI, curcumin promoted the expression of PTEN, reduced the proliferation of neuroglia cells, affected the expressions of CSPGs and improved the motor function. Conclusion: Curcumin can promote motor function recovery after SCI which is possibly by up-regulating the PTEN expression via the mTOR-STAT3 signaling pathway.

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