scholarly journals Exploring propriospinal neuron-mediated neural circuit plasticity using recombinant viruses after spinal cord injury

2021 ◽  
pp. 113962
Author(s):  
Lingxiao Deng ◽  
Baylen Ravenscraft ◽  
Xiao-Ming Xu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neural Circuit ◽  
Recombinant Viruses ◽  
Propriospinal Neuron ◽  
Cord Injury

scholarly journals Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Ying Wang ◽  
Wei Wu ◽  
Xiangbing Wu ◽  
Yan Sun ◽  
Yi P Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Targeted Delivery ◽  
Neural Circuit ◽  
Thoracic Spinal Cord ◽  
Spinal Cord Neurons ◽  
Thoracic Spinal ◽  
Virus Serotype ◽  
Cord Injury

Retrogradely-transported neurotrophin signaling plays an important role in regulating neural circuit specificity. Here we investigated whether targeted delivery of neurotrophin-3 (NT-3) to lumbar motoneurons (MNs) caudal to a thoracic (T10) contusive spinal cord injury (SCI) could modulate dendritic patterning and synapse formation of the lumbar MNs. In vitro, Adeno-associated virus serotype two overexpressing NT-3 (AAV-NT-3) induced NT-3 expression and neurite outgrowth in cultured spinal cord neurons. In vivo, targeted delivery of AAV-NT-3 into transiently demyelinated adult mouse sciatic nerves led to the retrograde transportation of NT-3 to the lumbar MNs, significantly attenuating SCI-induced lumbar MN dendritic atrophy. NT-3 enhanced sprouting and synaptic formation of descending serotonergic, dopaminergic, and propriospinal axons on lumbar MNs, parallel to improved behavioral recovery. Thus, retrogradely transported NT-3 stimulated remodeling of lumbar neural circuitry and synaptic connectivity remote to a thoracic SCI, supporting a role for retrograde transport of NT-3 as a potential therapeutic strategy for SCI.

scholarly journals Improvement of Rat Spinal Cord Injury Following Lentiviral Vector-Transduced Neural Stem/Progenitor Cells Derived from Human Epileptic Brain Tissue Transplantation with a Self-assembling Peptide Scaffold

2021 ◽  
Author(s):  
Sara Abdolahi ◽  
Hadi Aligholi ◽  
Azizollah Khodakaram-Tafti ◽  
Maryam Khaleghi Ghadiri ◽  
Walter Stummer ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cells ◽  
Neural Circuit ◽  
Lentiviral Vector ◽  
Host Tissue ◽  
Lesion Volume ◽  
Cell Based Therapy ◽  
Cord Injury ◽  
Neural Stem Progenitor Cells

AbstractSpinal cord injury (SCI) is a disabling neurological disorder that causes neural circuit dysfunction. Although various therapies have been applied to improve the neurological outcomes of SCI, little clinical progress has been achieved. Stem cell–based therapy aimed at restoring the lost cells and supporting micromilieu at the site of the injury has become a conceptually attractive option for tissue repair following SCI. Adult human neural stem/progenitor cells (hNS/PCs) were obtained from the epileptic human brain specimens. Induction of SCI was followed by the application of lentiviral vector-mediated green fluorescent protein–labeled hNS/PCs seeded in PuraMatrix peptide hydrogel (PM). The co-application of hNS/PCs and PM at the SCI injury site significantly enhanced cell survival and differentiation, reduced the lesion volume, and improved neurological functions compared to the control groups. Besides, the transplanted hNS/PCs seeded in PM revealed significantly higher migration abilities into the lesion site and the healthy host tissue as well as a greater differentiation into astrocytes and neurons in the vicinity of the lesion as well as in the host tissue. Our data suggest that the transplantation of hNS/PCs seeded in PM could be a promising approach to restore the damaged tissues and improve neurological functions after SCI.

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

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.

scholarly journals Targeting axon guidance cues for neural circuit repair after spinal cord injury

2020 ◽  
pp. 0271678X2096185
Author(s):  
Yimin Zou
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axon Guidance ◽  
Spinal Cord Injuries ◽  
Neural Circuit ◽  
Functional Restoration ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
The Many

At least two-thirds of spinal cord injury cases are anatomically incomplete, without complete spinal cord transection, although the initial injuries cause complete loss of sensory and motor functions. The malleability of neural circuits and networks allows varied extend of functional restoration in some individuals after successful rehabilitative training. However, in most cases, the efficiency and extent are both limited and uncertain, largely due to the many obstacles of repair. The restoration of function after anatomically incomplete injury is in part made possible by the growth of new axons or new axon branches through the spared spinal cord tissue and the new synaptic connections they make, either along the areas they grow through or in the areas they terminate. This review will discuss new progress on the understanding of the role of axon guidance molecules, particularly the Wnt family proteins, in spinal cord injury and how the knowledge and tools of axon guidance can be applied to increase the potential of recovery. These strategies, combined with others, such as neuroprotection and rehabilitation, may bring new promises. The recovery strategies for anatomically incomplete spinal cord injuries are relevant and may be applicable to traumatic brain injury and stroke.

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

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

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.

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

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.

Sign in / Sign up

Export Citation Format

Share Document