scholarly journals Macrophage centripetal migration drives spontaneous healing process after spinal cord injury

2019 ◽  
Vol 5 (5) ◽  
pp. eaav5086 ◽  
Author(s):  
Kazu Kobayakawa ◽  
Yasuyuki Ohkawa ◽  
Shingo Yoshizaki ◽  
Tetsuya Tamaru ◽  
Takeyuki Saito ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Healing Process ◽  
Inflammatory Cells ◽  
Time Lapse ◽  
Poor Functional Outcome ◽  
Wide Range ◽  
Cord Injury ◽  
Time Lapse Imaging ◽  
Centripetal Movement

Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury.

Improving sit-to-stand transition by the saddle-assistive device in the spinal cord injury: A case study

2021 ◽  
pp. 095441192110033
Author(s):  
Akbar Hojjati Najafabadi ◽  
Saeid Amini ◽  
Farzam Farahmand
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lower Limb ◽  
Reaction Force ◽  
Assistive Device ◽  
Limb Weakness ◽  
Sit To Stand ◽  
Lower Limb Weakness ◽  
Wide Range ◽  
Cord Injury

Physical problems caused by fractures, aging, stroke, and accidents can reduce foot power; these, in the long term, can dwindle the muscles of the waist, thighs, and legs. These conditions provide the basis for the invalidism of the harmed people. In this study, a saddle-walker was designed and evaluated to help people suffering from spinal cord injury and patients with lower limb weakness. This S-AD works based on body weight support against the previously report designs. This saddle-walker consisted of a non-powered four-wheel walker helping to walk and a powered mechanism for the sit-to-stand (STS) transfer. A set of experiments were done on the STS in the use of the standard walker and the saddle-assistive device(S-AD). A comparison of the results showed that this device could reduce the vertical ground reaction force (GRF) of the legs up to 70%. Using this device could help a wide range of patients with lower limb weakness and SCI patients in changing from sitting to standing.

Separation of the Perivascular Basement Membrane Provides a Conduit for Inflammatory Cells in a Mouse Spinal Cord Injury Model

2010 ◽  
Vol 27 (4) ◽  
pp. 739-751 ◽  
Author(s):  
Tomoyuki Takigawa ◽  
Tomoko Yonezawa ◽  
Teruhito Yoshitaka ◽  
Jun Minaguchi ◽  
Masae Kurosaki ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Basement Membrane ◽  
Inflammatory Cells ◽  
Mouse Spinal Cord ◽  
Spinal Cord Injury Model ◽  
Injury Model ◽  
Cord Injury

scholarly journals Efficacy of Virtual Reality Rehabilitation after Spinal Cord Injury: A Systematic Review

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Amanda Vitória Lacerda de Araújo ◽  
Jaqueline Freitas de Oliveira Neiva ◽  
Carlos Bandeira de Mello Monteiro ◽  
Fernando Henrique Magalhães
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Virtual Reality ◽  
Motor Function ◽  
Current Evidence ◽  
Pain Level ◽  
Positive Effects ◽  
Wide Range ◽  
Cord Injury ◽  
Aerobic Function

Background. Spinal cord injury (SCI) is often associated with long-term impairments related to functional limitations in the sensorimotor system. The use of virtual reality (VR) technology may lead to increased motivation and engagement, besides allowing a wide range of possible tasks/exercises to be implemented in rehabilitation programs. The present review aims to investigate the possible benefits and efficacy of VR-based rehabilitation in individuals with SCI. Methods. An electronically systematic search was performed in multiple databases (PubMed, BVS, Web of Science, Cochrane Central, and Scielo) up to May 2019. MESH terms and keywords were combined in a search strategy. Two reviewers independently selected the studies in accordance with eligibility criteria. The PEDro scale was used to score the methodological quality and risk of bias of the selected studies. Results. Twenty-five studies (including 482 participants, 47.6 ± 9.5 years, 73% male) were selected and discussed. Overall, the studies used VR devices in different rehabilitation protocols to improve motor function, driving skills, balance, aerobic function, and pain level, as well as psychological and motivational aspects. A large amount of heterogeneity was observed as to the study design, VR protocols, and outcome measures used. Only seven studies (28%) had an excellent/good quality of evidence. However, substantial evidence for significant positive effects associated with VR therapy was found in most of the studies (88%), with no adverse events (88%) being reported. Conclusion. Although the current evidence is limited, the findings suggest that VR-based rehabilitation in subjects with SCI may lead to positive effects on aerobic function, balance, pain level, and motor function recovery besides improving psychological/motivational aspects. Further high-quality studies are needed to provide a guideline to clinical practice and to draw robust conclusions about the potential benefits of VR therapy for SCI patients. Protocol details are registered on PROSPERO (registration number: CRD42016052629).

scholarly journals Betulinic Acid Inhibits ROS-Mediated Pyroptosis in Spinal Cord Injury by Augmenting Autophagy via the AMPK-mTOR-TFEB Signaling Pathway

2020 ◽  
Author(s):  
Chenyu Wu ◽  
Huanwen Chen ◽  
Rong Zhuang ◽  
Yongli Wang ◽  
Xinli Hu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Betulinic Acid ◽  
Neurological Diseases ◽  
Underlying Mechanism ◽  
Autophagy Flux ◽  
Wide Range ◽  
Cord Injury

Abstract Background：Spinal cord injury (SCI) results in a wide range of disabilities. Its complex pathophysiological process limits the effectiveness of many clinical treatments. Betulinic acid (BA) has been shown to be an effective treatment for some neurological diseases, but it has not been studied in SCI. In this study, we assessed the role of BA in SCI and investigated its underlying mechanism. Methods：Using a mouse model of SCI, survival and functional outcomes following injury were assessed. Western blotting, ELISA, and immunofluorescence techniques were employed to analyze levels of autophagy, mitophagy, and pyroptosis; ROS- and AMPK-related signaling pathways were also examined. Results：Our results showed that BA significantly improves functional recovery following SCI. Furthermore, autophagy, mitophagy, ROS-activity and pyroptosis were implicated in the mechanism of BA in the treatment of SCI. Specifically, our results suggest that BA restored autophagy flux following injury, which induces mitophagy to eliminate the accumulation of ROS and subsequently inhibits pyroptosis. Further mechanistic studies revealed that BA likely regulates autophagy and mitophagy via the AMPK-mTOR-TFEB signaling pathway. Conclusion: BA can significantly promote the recovery following SCI and that it may be a promising therapy for SCI.

scholarly journals Single-cell analysis of the cellular heterogeneity and interactions in the injured mouse spinal cord

2021 ◽  
Vol 218 (8) ◽  
Author(s):  
Lindsay M. Milich ◽  
James S. Choi ◽  
Christine Ryan ◽  
Susana R. Cerqueira ◽  
Sofia Benavides ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Healing Process ◽  
Cellular Heterogeneity ◽  
Wound Healing Process ◽  
Cellular Interactions ◽  
Mouse Spinal Cord ◽  
Cord Injury

The wound healing process that occurs after spinal cord injury is critical for maintaining tissue homeostasis and limiting tissue damage, but eventually results in a scar-like environment that is not conducive to regeneration and repair. A better understanding of this dichotomy is critical to developing effective therapeutics that target the appropriate pathobiology, but a major challenge has been the large cellular heterogeneity that results in immensely complex cellular interactions. In this study, we used single-cell RNA sequencing to assess virtually all cell types that comprise the mouse spinal cord injury site. In addition to discovering novel subpopulations, we used expression values of receptor–ligand pairs to identify signaling pathways that are predicted to regulate specific cellular interactions during angiogenesis, gliosis, and fibrosis. Our dataset is a valuable resource that provides novel mechanistic insight into the pathobiology of not only spinal cord injury but also other traumatic disorders of the CNS.

Mechanisms of Behavioral Changes After Spinal Cord Injury

2019 ◽  
Author(s):  
Karim Fouad ◽  
Abel Torres-Espín ◽  
Keith K. Fenrich
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Lesion Size ◽  
Behavioral Changes ◽  
Sensory Function ◽  
Wide Range ◽  
Cord Injury ◽  
New Treatment ◽  
Recovery Of Motor Function

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.

The ABLE Scale: The Development and Psychometric Properties of an Outcome Measure for the Spinal Cord Injury Population

2012 ◽  
Vol 92 (8) ◽  
pp. 1046-1054 ◽  
Author(s):  
Elizabeth M. Ardolino ◽  
Karen J. Hutchinson ◽  
Genevieve Pinto Zipp ◽  
MaryAnn Clark ◽  
Susan J. Harkema
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Psychometric Properties ◽  
Outcome Measures ◽  
Delphi Technique ◽  
Rasch Analysis ◽  
Item Difficulty ◽  
Wide Range ◽  
Cord Injury ◽  
Ceiling Effects

Background A paucity of information exists on the psychometric properties of several balance outcome measures. With the exception of the Modified Functional Reach Test, none of these balance outcome measures were developed specifically for the population with spinal cord injury (SCI). A new balance assessment tool for people with SCI, the Activity-based Balance Level Evaluation (ABLE scale), was developed and tested. Objective The purposes of this study were: (1) to develop a scale capturing the wide spectrum of functional ability following SCI and (2) to assess the initial psychometric properties of the scale using a Rasch analysis. Design A methodological research design was used to test the initial psychometric properties of the ABLE scale. Methods The Delphi technique was used to establish the original 28-item ABLE scale. People with SCI at each of 4 centers (n=104) were evaluated using the ABLE scale. A Rasch analysis was conducted to test for targeting, item difficulty, item bias, and unidimensionality. An analysis of variance was completed to test for discriminant validity. Results The Rasch analysis revealed a scale with minimal floor and ceiling effects and a wide range of item difficulty capturing the large scope of functional capacity after SCI. Multiple redundancies of item difficulty were observed. Limitations All raters were experienced physical therapists, which may have skewed the results. The sample size of 104 participants precluded a principal component analysis. Conclusion Development of an all-inclusive clinical instrument assessing balance in the SCI population was accomplished using the Delphi technique. Modifications of the ABLE scale based on the Rasch analysis yielded a 28-item scale with minimal floor or ceiling effects. Larger studies using the revised scale and factor analyses are necessary to establish unidimensionality and reduction of the total item number.

scholarly journals Therapeutic Effect of BDNF-Overexpressing Human Neural Stem Cells (F3.BDNF) in a Contusion Model of Spinal Cord Injury in Rats

2021 ◽  
Vol 22 (13) ◽  
pp. 6970
Author(s):  
Da-Jeong Chang ◽  
Hwi-Young Cho ◽  
Seyoung Hwang ◽  
Nayeon Lee ◽  
Chunggab Choi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Functional Recovery ◽  
Inflammatory Cells ◽  
Thoracic Spinal Cord ◽  
Human Neural Stem Cells ◽  
Neural Lineage ◽  
Cord Injury

The most common type of spinal cord injury is the contusion of the spinal cord, which causes progressive secondary tissue degeneration. In this study, we applied genetically modified human neural stem cells overexpressing BDNF (brain-derived neurotrophic factor) (F3.BDNF) to determine whether they can promote functional recovery in the spinal cord injury (SCI) model in rats. We transplanted F3.BDNF cells via intrathecal catheter delivery after a contusion of the thoracic spinal cord and found that they were migrated toward the injured spinal cord area by MR imaging. Transplanted F3.BDNF cells expressed neural lineage markers, such as NeuN, MBP, and GFAP and were functionally connected to the host neurons. The F3.BDNF-transplanted rats exhibited significantly improved locomotor functions compared with the sham group. This functional recovery was accompanied by an increased volume of spared myelination and decreased area of cystic cavity in the F3.BDNF group. We also observed that the F3.BDNF-transplanted rats showed reduced numbers of Iba1- and iNOS-positive inflammatory cells as well as GFAP-positive astrocytes. These results strongly suggest the transplantation of F3.BDNF cells can modulate inflammatory cells and glia activation and also improve the hyperalgesia following SCI.

scholarly journals Diversified transcriptional responses of myeloid and glial cells in spinal cord injury shaped by HDAC3 activity

2021 ◽  
Vol 7 (9) ◽  
pp. eabd8811
Author(s):  
Shalaka Wahane ◽  
Xianxiao Zhou ◽  
Xiang Zhou ◽  
Lei Guo ◽  
Marie-Sophie Friedl ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Microglial Cell ◽  
Source Population ◽  
Transcriptional Responses ◽  
Neural Repair ◽  
Histone Deacetylase 3 ◽  
Wide Range ◽  
Cord Injury ◽  
Epigenetic Regulator

The innate immune response influences neural repair after spinal cord injury (SCI). Here, we combined myeloid-specific transcriptomics and single-cell RNA sequencing to uncover not only a common core but also temporally distinct gene programs in injury-activated microglia and macrophages (IAM). Intriguingly, we detected a wide range of microglial cell states even in healthy spinal cord. Upon injury, IAM progressively acquired overall reparative, yet diversified transcriptional profiles, each comprising four transcriptional subtypes with specialized tasks. Notably, IAM have both distinct and common gene signatures as compared to neurodegeneration-associated microglia, both engaging phagocytosis, autophagy, and TyroBP pathways. We also identified an immediate response microglia subtype serving as a source population for microglial transformation and a proliferative subtype controlled by the epigenetic regulator histone deacetylase 3 (HDAC3). Together, our data unveil diversification of myeloid and glial subtypes in SCI and an extensive influence of HDAC3, which may be exploited to enhance functional recovery.

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