The Extent of Myelin Pathology Differs following Contusion and Transection Spinal Cord Injury

Siegenthaler, Monica M.; Tu, Michelle; Keirstead, Hans S.

doi:10.1089/neu.2007.0302

Cited by 74 publications

(59 citation statements)

References 59 publications

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“…A further study reported that in complete spinal cord transection rats, locomotor recovery after transplantation with both OPCs and human ESC-derived motor neuron progenitor cells was significantly greater than after treatment with either cell type alone [49]. Given that the application of stem cells and their progenitors for transplantation is currently in its infancy, and that SCI pathology differs between contusion and transection [50], these findings indicate that neural cells in an appropriate lineage should be transplanted according to the degree and/or type of SCI.…”

Section: Discussionmentioning

confidence: 99%

Treatment of a Mouse Model of Spinal Cord Injury by Transplantation of Human Induced Pluripotent Stem Cell-Derived Long-Term Self-Renewing Neuroepithelial-Like Stem Cells

et al. 2012

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Because of their ability to self-renew, to differentiate into multiple lineages, and to migrate toward a damaged site, neural stem cells (NSCs), which can be derived from various sources such as fetal tissues and embryonic stem cells, are currently considered to be promising components of cell replacement strategies aimed at treating injuries of the central nervous system, including the spinal cord. Despite their efficiency in promoting functional recovery, these NSCs are not homogeneous and possess variable characteristics depending on their derivation protocols. The advent of induced pluripotent stem (iPS) cells has provided new prospects for regenerative medicine. We used a recently developed robust and stable protocol for the generation of long-term, self-renewing, neuroepithelial-like stem cells from human iPS cells (hiPS-lt-NES cells), which can provide a homogeneous and well-defined population of NSCs for standardized analysis. Here, we show that transplanted hiPS-lt-NES cells differentiate into neural lineages in the mouse model of spinal cord injury (SCI) and promote functional recovery of hind limb motor function. Furthermore, using two different neuronal tracers and ablation of the transplanted cells, we revealed that transplanted hiPS-lt-NES cell-derived neurons, together with the surviving endogenous neurons, contributed to restored motor function. Both types of neurons reconstructed the corticospinal tract by forming synaptic connections and integrating neuronal circuits. Our findings indicate that hiPS-lt-NES transplantation represents a promising avenue for effective cell-based treatment of SCI. Disclosure of potential conflicts of interest is found at the end of this article.

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Section: Discussionmentioning

confidence: 99%

Treatment of a Mouse Model of Spinal Cord Injury by Transplantation of Human Induced Pluripotent Stem Cell-Derived Long-Term Self-Renewing Neuroepithelial-Like Stem Cells

et al. 2012

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“…10 The biology of contusion also appears to be different from hemisection or transection models. 11 Iseda, et al compared the effect of intraspinal chondroitinase ABC injection on neuroregeneration separately in hemisection and contusion models. 4 Axonal regeneration was observed in the neuronal bridge in hemisection but not the contusion SCI group.…”

Section: Introductionmentioning

confidence: 99%

A Contusion Model of Severe Spinal Cord Injury in Rats

Krishna

Andrews

Jin

et al. 2013

JoVE

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The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is described to obtain a consistent model of severe SCI. Use of a stereotactic frame and computer controlled impactor allows for creation of reproducible injury. Hypothermia and urinary tract infection pose significant challenges in the post-operative period. Careful monitoring of animals with daily weight recording and bladder expression allows for early detection of post-operative complications. The functional results of this contusion model are equivalent to transection models. The contusion model can be utilized to evaluate the efficacy of both neuroprotective and neuroregenerative approaches. Video LinkThe video component of this article can be found at

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“…31 Furthermore, the level of injury can affect pathophysiological events, especially when neurons are evaluated after injury, and the amount of apoptosis after axotomy depends on the distance of the injured site from the cell body. 32 Moreover, in compression/ contusion model of injury, the applied force and duration of compression are the most effective factors on the severity of injury.…”

Section: Methods Of Allocation To Treatmentmentioning

confidence: 99%

Potential variables affecting the quality of animal studies regarding pathophysiology of traumatic spinal cord injuries

et al. 2015

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Study design: This is a Delphi study. Objectives: Defining variables that potentially influence the outcomes of an animal study regarding pathophysiology of traumatic spinal cord injury (TSCI). Setting: This study was conducted in Iran. Methods: A modified two-round Delphi study was conducted. As the first round, an initial questionnaire was developed on the basis of literature and a series of focus group discussions. In the second round, the participants were asked to score the items through a 10-point scale. Consensus was achieved through the following criteria: (1) the median of scores has to be at 7.5 or higher, and (2) at least 70% of participants need to rate 7 or higher. Also, the inter-rater reliability analysis was performed to determine consistency among raters using the Kappa coefficient and Cronbach's alpha. Results: Twenty-one experts participated in our study. From the first round of the study, a 47-item checklist was developed. By considering the aforementioned criteria for consensus building on extremely important factors, we reached a 15-item checklist including species, strain, method and level of injury, control group, genetic background, severity of injury, attrition, use of appropriate test, blindness, method of allocation to treatments, regulation and ethics, age/weight, bladder expression, number of animals/group and statistics. The inter-rater reliability for the raters was found to be Kappa = 0.82 (Po0.001). A Cronbach's alpha of 0.9 for all the questions indicated high internal consistency. Conclusion: This study introduces a checklist of variables that potentially influence the outcomes of animal studies regarding TSCI pathophysiology and describe its validity and reliability. Spinal Cord (2016) 54, 579-583; doi:10.1038/sc.2015.215; published online 22 December 2015 INTRODUCTIONTraumatic spinal cord injury (TSCI) is a devastating injury to the patient, family and society, as a TSCI results in multi-system complications, impaired health-related quality of life and poor prognosis for neurologic recovery. 1-3 The incidence of TSCI ranges from 3.6 to 195.4 patients per million around the world 4 and 25.5 per million per year in developing countries. 5 A prerequisite to the development of effective therapies for TSCI is a detailed understanding of the pathophysiological events occurring after injury. The pathophysiology of TSCI can be well divided into two phases, a primary and a secondary injury. The primary injury involves the initial mechanical damage, which is followed by a delayed onset of a secondary phase comprising a cascade of molecular and cellular events that inhibits the regeneration and also extends the injured site. As a result of the many technical limitations associated with the study of TSCI pathophysiology in humans, almost all of our detailed understanding of TSCI pathophysiology is based on animal studies. Translation of the obtained outcomes to the clinic could be achieved through well-designed animal studies and consideration of the variables, which are decisive in det...

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The Extent of Myelin Pathology Differs following Contusion and Transection Spinal Cord Injury

Cited by 74 publications

References 59 publications

Treatment of a Mouse Model of Spinal Cord Injury by Transplantation of Human Induced Pluripotent Stem Cell-Derived Long-Term Self-Renewing Neuroepithelial-Like Stem Cells

Treatment of a Mouse Model of Spinal Cord Injury by Transplantation of Human Induced Pluripotent Stem Cell-Derived Long-Term Self-Renewing Neuroepithelial-Like Stem Cells

A Contusion Model of Severe Spinal Cord Injury in Rats

Potential variables affecting the quality of animal studies regarding pathophysiology of traumatic spinal cord injuries

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