Novel System to Monitor In Vivo Neural Graft Activity After Spinal Cord Injury

AbstractExpectations for neural stem/progenitor cell (NS/PC) transplantation as a treatment for spinal cord injury (SCI) are increasing. However, whether and how grafted cells are incorporated into the host neural circuit and contribute to motor function recovery remain unknown. The aim of this project was to establish a novel non-invasive in vivo imaging system to visualize the activity of neural grafts by which we can simultaneously demonstrate the circuit-level integration between the graft and host, and the contribution of graft neuronal activity to host behaviour. We introduced Akaluc, a newly engineered luciferase, under control of a potent neuronal activity-dependent synthetic promoter, E-SARE, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we reveal that the activity of grafted cells was integrated with host behaviour and driven by host neural circuit inputs. This non-invasive system is expected to help elucidate the therapeutic mechanism of cell transplantation treatment for SCI and determine better therapy techniques that maximize the function of cells in the host circuit.

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Novel System to Monitor In Vivo Neural Graft Activity After Spinal Cord Injury

10.21203/rs.3.rs-899013/v1 ◽

2021 ◽

Author(s):

Kentaro Ago ◽

Narihito Nagoshi ◽

Kent Imaizumi ◽

Takahiro Kitagawa ◽

Momotaro Kawai ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuronal Activity ◽

Neural Circuit ◽

Imaging System ◽

Non Invasive ◽

Cord Injury ◽

Neural Graft ◽

Host Behaviour

Abstract Expectations for neural stem/progenitor cell (NS/PC) transplantation as a treatment for spinal cord injury (SCI) are increasing. However, whether and how grafted cells are incorporated into the host neural circuit and contribute to motor function recovery remain unknown. The aim of this project was to establish a novel non-invasive in vivo imaging system to visualize the activity of neural grafts by which we can simultaneously demonstrate the circuit-level integration between the graft and host, and the contribution of graft neuronal activity to host behaviour. We introduced Akaluc, a newly engineered luciferase, under control of a potent neuronal activity-dependent synthetic promoter, E-SARE, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we reveal that the activity of grafted cells was integrated with host behaviour and driven by host neural circuit inputs. This non-invasive system is expected to help elucidate the therapeutic mechanism of cell transplantation treatment for SCI and determine better therapy techniques that maximize the function of cells in the host circuit.

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Cortical layer-specific modulation of neuronal activity after sensory deprivation due to spinal cord injury

10.1101/2020.12.28.424612 ◽

2020 ◽

Author(s):

Marta Zaforas ◽

Juliana M Rosa ◽

Elena Alonso-Calviño ◽

Elena Fernández-López ◽

Claudia Miguel-Quesada ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuronal Activity ◽

Large Scale ◽

Sensory Deprivation ◽

Sensory Stimulation ◽

Gamma Oscillations ◽

Cortical Layer ◽

Cord Injury

SummaryCortical areas have the capacity of large-scale reorganization following sensory deprivation. However, it remains unclear whether this is a unique process that homogenously affects the entire deprived region or it is suitable to changes depending on local circuitries across layers. By using in vivo electrophysiology to record neuronal activity simultaneously across cortical depth, we showed that sensory deprivation due to spinal cord injury induces layer-specific changes in both spontaneous and evoked-activity. While supragranular layers specifically increased gamma oscillations and the ability to initiate up-states during spontaneous activity, infragranular layers displayed increased, faster and delayed evoked-responses to sensory stimulation. Therefore, sensory deprivation immediately modifies local circuitries allowing supragranular layers to better integrate spontaneous corticocortical information to maintain column excitability, and infragranular layers to better integrate evoked-sensory inputs to preserve subcortical outputs. These layer-specific changes may guide long-term alterations in excitability and plasticity associated to network rearrangements and the appearance of sensory pathologies associated with spinal cord injury.

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Transplantation of Wnt5a-modified NSCs promotes tissue repair and locomotor functional recovery after spinal cord injury

Experimental & Molecular Medicine ◽

10.1038/s12276-020-00536-0 ◽

2020 ◽

Vol 52 (12) ◽

pp. 2020-2033

Author(s):

Xiang Li ◽

Zhiming Peng ◽

Lingli Long ◽

Xiaofang Lu ◽

Kai Zhu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuronal Differentiation ◽

Neural Circuit ◽

Treatment Strategies ◽

Cord Injury ◽

Potential Strategy ◽

Novel Treatment Strategies ◽

Spinal Cord Repair

AbstractTraditional therapeutic strategies for spinal cord injury (SCI) are insufficient to repair locomotor function because of the failure of axonal reconnection and neuronal regeneration in the injured central nervous system (CNS). Neural stem cell (NSC) transplantation has been considered a potential strategy and is generally feasible for repairing the neural circuit after SCI; however, the most formidable problem is that the neuronal differentiation rate of NSCs is quite limited. Therefore, it is essential to induce the neuronal differentiation of NSCs and improve the differentiation rate of NSCs in spinal cord repair. Our results demonstrate that both Wnt5a and miRNA200b-3p could promote NSC differentiation into neurons and that Wnt5a upregulated miRNA200b-3p expression through MAPK/JNK signaling to promote NSC differentiation into neurons. Wnt5a could reduce RhoA expression by upregulating miRNA200b-3p expression to inhibit activation of the RhoA/Rock signaling pathway, which has been reported to suppress neuronal differentiation. Overexpression of RhoA abolished the neurogenic capacity of Wnt5a and miRNA200b-3p. In vivo, miRNA200b-3p was critical for Wnt5a-induced NSC differentiation into neurons to promote motor functional and histological recovery after SCI by suppressing RhoA/Rock signaling. These findings provide more insight into SCI and help with the identification of novel treatment strategies.

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Targeting ependymal stem cells in vivo as a non-invasive therapy for spinal cord injury

Disease Models & Mechanisms ◽

10.1242/dmm.006643 ◽

2010 ◽

Vol 3 (11-12) ◽

pp. 667-668 ◽

Cited By ~ 8

Author(s):

A. Barreiro-Iglesias

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Invasive Therapy ◽

Non Invasive ◽

Cord Injury

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Faculty Opinions recommendation of Effect of vascular endothelial growth factor treatment in experimental traumatic spinal cord injury: in vivo longitudinal assessment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.9908956.11172056 ◽

2011 ◽

Author(s):

Jose V Lafuente ◽

Enrike Argandoña

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Vascular Endothelial Growth Factor ◽

Traumatic Spinal Cord Injury ◽

Vascular Endothelial ◽

Longitudinal Assessment ◽

Cord Injury ◽

Endothelial Growth Factor ◽

Growth Factor Treatment

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Abstract #29: Scaling Spinal Cord injury Models for Non-invasive Stimulation

Brain Stimulation ◽

10.1016/j.brs.2018.12.036 ◽

2019 ◽

Vol 12 (2) ◽

pp. e10-e11

Author(s):

Dennis Q. Truong ◽

Catherine Maglione ◽

Yishai Valter ◽

Louis Zannou ◽

A. Duke Shereen ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Non Invasive ◽

Cord Injury ◽

Injury Models

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Non-invasive approaches to functional recovery after spinal cord injury: Therapeutic targets and multimodal device interventions

Experimental Neurology ◽

10.1016/j.expneurol.2021.113612 ◽

2021 ◽

Vol 339 ◽

pp. 113612

Author(s):

Claudio Pizzolato ◽

Mehmet A. Gunduz ◽

Dinesh Palipana ◽

Jingnan Wu ◽

Gary Grant ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Functional Recovery ◽

Therapeutic Targets ◽

Non Invasive ◽

Cord Injury

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A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽

10.3390/polym12102245 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2245

Author(s):

Jue-Zong Yeh ◽

Ding-Han Wang ◽

Juin-Hong Cherng ◽

Yi-Wen Wang ◽

Gang-Yi Fan ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Rat Model ◽

Neural Plasticity ◽

Collagen Scaffold ◽

Glial Scar ◽

Beneficial Effects ◽

Cord Injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

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