A controlled spinal cord contusion for the rhesus macaque monkey

Liu, Wei; Yan, Guofeng; Li, Yao; Shields, Lisa B. E.; Walker, Melissa J.; Chen, Kemin; Huang, Wei; Kong, Maiying; Lu, Yi; Brommer, Benedikt; Chen, Xuejin; Xu, Xiao Ming; Shields, Christopher B.

doi:10.1016/j.expneurol.2016.02.008

Cited by 38 publications

(22 citation statements)

References 45 publications

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“…Gene expression analysis in marmosets also revealed a delayed glial scar formation and a prolonged inflammatory response versus rodents, further supporting temporal differences in glial response after injury among species [17]. In the lesional penumbra, no strong astrocytic glial scars have been observed 6 months after spinal cord contusion in rhesus macaques, but strong GFAP immunoreactivity is present in the spared white matter [20].…”

Section: Introductionmentioning

confidence: 64%

“…Quadrupedalism in primates, particularly in M. murinus, is well adapted for walking on branches and differs from other mammals: they prefer a diagonal sequence to a lateral sequence [43]. Analysis of locomotion sequence in spinal cord injured primates walking quadrupedally had been done previously either on treadmill [13] or in a walking corridor [20]. The CatWalk system was originally designed for rodents that present a regularity index of 100% before lesion, but noninjured M. murinus scored 90%, which we established as the Bnormal^value against which to compare functional recovery.…”

Section: Discussionmentioning

confidence: 99%

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A Novel Translational Model of Spinal Cord Injury in Nonhuman Primate

et al. 2018

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Spinal cord injuries (SCI) lead to major disabilities affecting > 2.5 million people worldwide. Major shortcomings in clinical translation result from multiple factors, including species differences, development of moderately predictive animal models, and differences in methodologies between preclinical and clinical studies. To overcome these obstacles, we first conducted a comparative neuroanatomical analysis of the spinal cord between mice, Microcebus murinus (a nonhuman primate), and humans. Next, we developed and characterized a new model of lateral spinal cord hemisection in M. murinus. Over a 3-month period after SCI, we carried out a detailed, longitudinal, behavioral follow-up associated with in vivo magnetic resonance imaging (H-MRI) monitoring. Then, we compared lesion extension and tissue alteration using 3 methods: in vivo H-MRI, ex vivoH-MRI, and classical histology. The general organization and glial cell distribution/morphology in the spinal cord of M. murinus closely resembles that of humans. Animals assessed at different stages following lateral hemisection of the spinal cord presented specific motor deficits and spinal cord tissue alterations. We also found a close correlation between H-MRI signal and microglia reactivity and/or associated post-trauma phenomena. Spinal cord hemisection in M. murinus provides a reliable new nonhuman primate model that can be used to promote translational research on SCI and represents a novel and more affordable alternative to larger primates.

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Section: Introductionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

A Novel Translational Model of Spinal Cord Injury in Nonhuman Primate

et al. 2018

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“…Initial studies of the application of DTI in non-human primates for the investigation of TBI are ongoing. Seminal work has shown that DTI can provide outcome measures in non-human primates models of traumatic spinal cord injury (Ma et al, 2016 ) and the remodeling of brain circuits upon hippocampal damage (Meng et al, 2018 ). Although non-human primate models of TBI has been established (e.g., King et al, 2010 ), the logistics and the ethics of non-human primates have so far limited the availability for DTI investigations.…”

Section: Applications To Models Of Neurodegenerative Diseasesmentioning

confidence: 99%

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

et al. 2020

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The understanding of human and non-human microstructural brain alterations in the course of neurodegenerative diseases has substantially improved by the non-invasive magnetic resonance imaging (MRI) technique of diffusion tensor imaging (DTI). Animal models (including disease or knockout models) allow for a variety of experimental manipulations, which are not applicable to humans. Thus, the DTI approach provides a promising tool for cross-species cross-sectional and longitudinal investigations of the neurobiological targets and mechanisms of neurodegeneration. This overview with a systematic review focuses on the principles of DTI analysis as used in studies at the group level in living preclinical models of neurodegeneration. The translational aspect from in-vivo animal models toward (clinical) applications in humans is covered as well as the DTI-based research of the non-human brains' microstructure, the methodological aspects in data processing and analysis, and data interpretation at different abstraction levels. The aim of integrating DTI in multiparametric or multimodal imaging protocols will allow the interrogation of DTI data in terms of directional flow of information and may identify the microstructural underpinnings of neurodegeneration-related patterns.

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“…Rodents are commonly used for its availability and number of interventions possible, but their SCI models are different from actual SCIs in humans (Nardone et al, ). Ma et al () utilized a spinal contusion model for rhesus monkeys. The advantage of such a model is the physiological and genetic similarities between monkeys and humans, and the disadvantages are the high cost and the replicability.…”

Section: Introductionmentioning

confidence: 99%

Operation spinal cord regeneration: Patterning information residing in extracellular matrix glycosaminoglycans

Baker-Nigh

Sun

2020

Brain and Behavior

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Introduction Spinal cord injuries are devastating, with many complications beyond paralysis and loss of sensory function. Although spinal cord regeneration can revolutionize treatment for spinal cord injuries, the goal has not yet been achieved. The regenerative mechanism of axolotls demonstrates that the regeneration is a repeat of developmental process that all animals have all the genes, but axolotls have both the genes and the patterning information to do it at the adult stage. Methods A narrative review was conducted. Relevant studies were collected via an English‐language PubMed database search and those known to the authors. Results Research during the past 30 years reveals that growth factors, along with spinal cord extracellular matrix, especially glycosaminoglycans, regulates axonal regrowth. Degrading chondroitin sulfate glycosaminoglycans by injecting the bacterial enzyme chondroitinase improves axonal sprouting and functional recovery after spinal cord injury in both rodents and rhesus monkeys. Furthermore, the brain is one of the first organs to develop during the embryonic period, and heparan sulfate glycosaminoglycans are key molecules required for brain development. Conclusions Patterning information residing in glycosaminoglycans might be key elements in restricting spinal cord regeneration. A recommended solution is not to edit the human genome, considering the conserved signaling pathways between animals, but to take advantage of the regenerative mechanism of axolotls and the current knowledge about the pattern‐forming glycosaminoglycans for successful spinal cord regeneration and clinical applications.

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A controlled spinal cord contusion for the rhesus macaque monkey

Cited by 38 publications

References 45 publications

A Novel Translational Model of Spinal Cord Injury in Nonhuman Primate

A Novel Translational Model of Spinal Cord Injury in Nonhuman Primate

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

Operation spinal cord regeneration: Patterning information residing in extracellular matrix glycosaminoglycans

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