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.

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.

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).

Spinal cord injury and neural repair: focus on neuroregenerative approaches for spinal cord injury

2009 ◽  
Vol 18 (5) ◽  
pp. 663-673 ◽  
Author(s):  
Darryl C Baptiste ◽  
Allyson Tighe ◽  
Michael G Fehlings
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neural Repair ◽  
Cord Injury

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.

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.

scholarly journals Elevated Serum Melatonin under Constant Darkness Enhances Neural Repair in Spinal Cord Injury through Regulation of Circadian Clock Proteins Expression

2019 ◽  
Vol 8 (2) ◽  
pp. 135 ◽  
Author(s):  
Yunkyung Hong ◽  
Yunho Jin ◽  
Kanghui Park ◽  
Jeonghyun Choi ◽  
Hyunbon Kang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Circadian Clock ◽  
Acute Phase ◽  
Constant Darkness ◽  
Neural Repair ◽  
Melatonin Concentration ◽  
Cord Injury ◽  
Constant Dark ◽  
Endogenous Melatonin

We investigated the effects of environmental lighting conditions regulating endogenous melatonin production on neural repair, following experimental spinal cord injury (SCI). Rats were divided into three groups randomly: the SCI + L/D (12/12-h light/dark), SCI + LL (24-h constant light), and SCI + DD (24-h constant dark) groups. Controlled light/dark cycle was pre-applied 2 weeks before induction of spinal cord injury. There was a significant increase in motor recovery as well as body weight from postoperative day (POD) 7 under constant darkness. However, spontaneous elevation of endogenous melatonin in cerebrospinal fluid was seen at POD 3 in all of the SCI rats, which was enhanced in SCI + DD group. Augmented melatonin concentration under constant dark condition resulted in facilitation of neuronal differentiation as well as inhibition of primary cell death. In the rostrocaudal region, elevated endogenous melatonin concentration promoted neural remodeling in acute phase including oligodendrogenesis, excitatory synaptic formation, and axonal outgrowth. The changes were mediated via NAS-TrkB-AKT/ERK signal transduction co-regulated by the circadian clock mechanism, leading to rapid motor recovery. In contrast, exposure to constant light exacerbated the inflammatory responses and neuroglial loss. These results suggest that light/dark control in the acute phase might be a considerable environmental factor for a favorable prognosis after SCI.

Rehabilitation Medicine Implications of Stem Cell Therapy in Spinal Cord Injury–A Review

2013 ◽  
Vol 24 (1) ◽  
pp. 9-15
Author(s):  
U Singh ◽  
Gita Handa ◽  
K B Sumalatha
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Animal Studies ◽  
Rehabilitation Medicine ◽  
Neural Repair ◽  
Cord Injury ◽  
Task Oriented

Abstract The life expectancy in spinal cord injury has increased but no cure has been found yet. Stem cell therapy in the spinal cord injury stands high hopes of neural repair and regeneration and getting back to normal life. But for its fruitful result it is essential to know the pathophysiology of the spinal cord injury and also the treatment should be appropriately timed according to the stages of injury. Regular follow-up of these patients is very important as stem cell therapy alone without appropriate rehabilitation may not only result in failure of therapy but also patients may end up in complications such as UTI, bed sores etc. Role of rehab in spinal cord injury with respect to physiological and task oriented neuroplasticity has shown benefits in animal studies. Rehabilitation programme integrated with the stem cell therapy may help to improve the functional outcome.

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