scholarly journals The Application of Omics Technologies to Study Axon Regeneration and CNS Repair

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 311 ◽  
Author(s):  
Andrea Tedeschi ◽  
Phillip G Popovich
Keyword(s):  
Spinal Cord ◽  
Molecular Mechanisms ◽  
Spinal Cord Injuries ◽  
New Technologies ◽  
Axon Regeneration ◽  
Imaging Techniques ◽  
Permanent Disability ◽  
Cord Injury ◽  
Technical Advances ◽  
And Function

Traumatic brain and spinal cord injuries cause permanent disability. Although progress has been made in understanding the cellular and molecular mechanisms underlying the pathophysiological changes that affect both structure and function after injury to the brain or spinal cord, there are currently no cures for either condition. This may change with the development and application of multi-layer omics, new sophisticated bioinformatics tools, and cutting-edge imaging techniques. Already, these technical advances, when combined, are revealing an unprecedented number of novel cellular and molecular targets that could be manipulated alone or in combination to repair the injured central nervous system with precision. In this review, we highlight recent advances in applying these new technologies to the study of axon regeneration and rebuilding of injured neural circuitry. We then discuss the challenges ahead to translate results produced by these technologies into clinical application to help improve the lives of individuals who have a brain or spinal cord injury.

scholarly journals Regeneration of Corticospinal Axons into Neural Progenitor Cell Grafts After Spinal Cord Injury

2020 ◽  
Vol 15 ◽  
pp. 263310552097400
Author(s):  
Gunnar HD Poplawski ◽  
Mark H Tuszynski
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
Spinal Cord Injuries ◽  
Axon Regeneration ◽  
Stem Cell Differentiation ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Cord Injury

Spinal cord injuries leave patients with lifelong paralysis. To date, there are no therapies that promote the critical step required for the recovery of voluntary motor function: corticospinal axon regeneration. Spinal cord-derived neural progenitor cell (NPC) grafts integrate into the injured host spinal cord, enable robust corticospinal axon regeneration, and restore forelimb function following spinal cord injury in rodents. Consequently, engineered stem cell differentiation and transplantation techniques harbor promising potential for the design and implementation of therapies promoting corticospinal axon regeneration. However, in order to optimize the outcome of clinical trials, it is critical to fully understand the cellular and molecular mechanisms underlying this regeneration. Our recent study highlights the unexpected intrinsic potential of corticospinal neurons to regenerate and allows us to investigate new hypotheses exploiting this newly discovered potential.

scholarly journals Three-dimensional aligned nanofibers-hydrogel scaffold for controlled non-viral drug/gene delivery to direct axon regeneration in spinal cord injury treatment

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lan Huong Nguyen ◽  
Mingyong Gao ◽  
Junquan Lin ◽  
Wutian Wu ◽  
Jun Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Axon Regeneration ◽  
Three Dimensional ◽  
Neurological Dysfunction ◽  
Post Injury ◽  
Hydrogel Scaffold ◽  
Cord Injury ◽  
Aligned Nanofibers ◽  
Injury Treatment

Abstract Spinal cord injuries (SCI) often lead to persistent neurological dysfunction due to failure in axon regeneration. Unfortunately, currently established treatments, such as direct drug administration, do not effectively treat SCI due to rapid drug clearance from our bodies. Here, we introduce a three-dimensional aligned nanofibers-hydrogel scaffold as a bio-functionalized platform to provide sustained non-viral delivery of proteins and nucleic acid therapeutics (small non-coding RNAs), along with synergistic contact guidance for nerve injury treatment. A hemi-incision model at cervical level 5 in the rat spinal cord was chosen to evaluate the efficacy of this scaffold design. Specifically, aligned axon regeneration was observed as early as one week post-injury. In addition, no excessive inflammatory response and scar tissue formation was triggered. Taken together, our results demonstrate the potential of our scaffold for neural tissue engineering applications.

scholarly journals Retrograde Activation of the Extrinsic Apoptotic Pathway in Spinal-Projecting Neurons after a Complete Spinal Cord Injury in Lampreys

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Antón Barreiro-Iglesias ◽  
Daniel Sobrido-Cameán ◽  
Michael I. Shifman
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Extrinsic Pathway ◽  
Apoptotic Pathway ◽  
Permanent Disability ◽  
Descending Neurons ◽  
Neuronal Soma ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition that leads to permanent disability because injured axons do not regenerate across the trauma zone to reconnect to their targets. A prerequisite for axonal regeneration will be the prevention of retrograde degeneration that could lead to neuronal death. However, the specific molecular mechanisms of axotomy-induced degeneration of spinal-projecting neurons have not been elucidated yet. In lampreys, SCI induces the apoptotic death of identifiable descending neurons that are “bad regenerators/poor survivors” after SCI. Here, we investigated the apoptotic process activated in identifiable descending neurons of lampreys after SCI. For this, we studied caspase activation by using fluorochrome-labeled inhibitors of caspases, the degeneration of spinal-projecting neurons using Fluro-Jade C staining, and the involvement of the intrinsic apoptotic pathway by means of cytochrome c and Vαdouble immunofluorescence. Our results provide evidence that, after SCI, bad-regenerating spinal cord-projecting neurons slowly degenerate and that the extrinsic pathway of apoptosis is involved in this process. Experiments using the microtubule stabilizer Taxol showed that caspase-8 signaling is retrogradely transported by microtubules from the site of axotomy to the neuronal soma. Preventing the activation of this process could be an important therapeutic approach after SCI in mammals.

scholarly journals Neuroprotective and Neurorestorative Processes after Spinal Cord Injury: The Case of the Bulbospinal Respiratory Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-15
Author(s):  
Anne Kastner ◽  
Valéry Matarazzo
Keyword(s):  
Spinal Cord ◽  
Molecular Mechanisms ◽  
Spinal Cord Injuries ◽  
Cervical Spinal Cord ◽  
Axon Growth ◽  
Respiratory Neurons ◽  
Partial Recovery ◽  
Respiratory Drive ◽  
Phrenic Motoneurons ◽  
Cord Injury

High cervical spinal cord injuries interrupt the bulbospinal respiratory pathways projecting to the cervical phrenic motoneurons resulting in important respiratory defects. In the case of a lateralized injury that maintains the respiratory drive on the opposite side, a partial recovery of the ipsilateral respiratory function occurs spontaneously over time, as observed in animal models. The rodent respiratory system is therefore a relevant model to investigate the neuroplastic and neuroprotective mechanisms that will trigger such phrenic motoneurons reactivation by supraspinal pathways. Since part of this recovery is dependent on the damaged side of the spinal cord, the present review highlights our current understanding of the anatomical neuroplasticity processes that are developed by the surviving damaged bulbospinal neurons, notably axonal sprouting and rerouting. Such anatomical neuroplasticity relies also on coordinated molecular mechanisms at the level of the axotomized bulbospinal neurons that will promote both neuroprotection and axon growth.

scholarly journals Lentiviral Vectors Delivered with Biomaterials as Therapeutics for Spinal Cord Injury

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2102
Author(s):  
Ciara Shortiss ◽  
Linda Howard ◽  
Siobhan S. McMahon
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Lentiviral Vectors ◽  
Therapeutic Effects ◽  
Nucleic Acid Delivery ◽  
Permanent Disability ◽  
Cord Injury ◽  
Socioeconomic Burden ◽  
Superior Approach

Spinal cord injury (SCI) is a devastating trauma that can cause permanent disability, life-long chronic issues for sufferers and is a big socioeconomic burden. Regenerative medicine aims to overcome injury caused deficits and restore function after SCI through gene therapy and tissue engineering approaches. SCI has a multifaceted pathophysiology. Due to this, producing therapies that target multiple different cellular and molecular mechanisms might prove to be a superior approach in attempts at regeneration. Both biomaterials and nucleic acid delivery via lentiviral vectors (LVs) have proven to promote repair and restoration of function post SCI in animal models. Studies indicate that a combination of biomaterials and LVs is more effective than either approach alone. This review presents studies supporting the use of LVs and LVs delivered with biomaterials in therapies for SCI and summarises methods to combine LVs with biomaterials for SCI treatment. By summarising this knowledge this review aims to demonstrate how LV delivery with biomaterials can augment/compliment both LV and biomaterial therapeutic effects in SCI.

Recent Developments in Regenerative Strategies to Treat Spinal Cord Injuries

Neurotrauma ◽  
2018 ◽  
pp. 423-430
Author(s):  
Wenjing Sun ◽  
Andrea Tedeschi ◽  
Riyi Shi
Keyword(s):  
Spinal Cord ◽  
Molecular Mechanisms ◽  
Spinal Cord Injuries ◽  
Diffuse Axonal Injury ◽  
Regeneration Failure ◽  
Cord Injury ◽  
Recent Developments ◽  
Near Future ◽  
Spinal Cord Repair

Trauma to the adult mammalian central nervous system (CNS) causes diffuse axonal injury that results in devastating long-term disabilities due to limited sprouting and axon regeneration failure. No therapeutic strategy that restores neurological function is currently available for individuals who have suffered damage to their spinal cords. The past few decades have witnessed major advances in the technology used to study CNS development, homeostasis, and disease. A better understanding of the cellular and molecular mechanisms underlying axonal growth and regeneration failure has allowed the development of several regenerative strategies that may change the way we treat spinal cord injury (SCI) in the near future. This chapter summarizes recent progress in spinal cord repair and regeneration, including combinatorial strategies promoting axonal sprouting, regeneration, formation, and consolidation of neuronal circuits as well as cellular replacement after injury.

‘In a blink of an eye your life can change’: experiences of players sustaining a rugby-related acute spinal cord injury

2018 ◽  
Vol 25 (4) ◽  
pp. 313-320 ◽  
Author(s):  
Marelise Badenhorst ◽  
Evert Verhagen ◽  
Michael Ian Lambert ◽  
Willem van Mechelen ◽  
James Craig Brown
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
First Responders ◽  
Signs And Symptoms ◽  
Rugby Union ◽  
Structured Interviews ◽  
Contributing Factors ◽  
Permanent Disability ◽  
Cord Injury ◽  
Prevention Programmes

BackgroundThough rare, rugby union carries a risk for serious injuries such as acute spinal cord injuries (ASCI), which may result in permanent disability. Various studies have investigated injury mechanisms, prevention programmes and immediate medical management of these injuries. However, relatively scant attention has been placed on the player’s experience of such an injury and the importance of context.AimThe aim of this study was to explore the injury experience and its related context, as perceived by the catastrophically injured player.MethodsA qualitative approach was followed to explore the immediate, postevent injury experience. Semi-structured interviews were conducted with 48 (n=48) players who had sustained a rugby-related ASCI.ResultsFour themes were derived from the data. Participants described the context around the injury incident, which may be valuable to help understand the mechanism of injury and potentially minimise risk. Participants also described certain contributing factors to their injury, which included descriptions of foul play and aggression, unaccustomed playing positions, pressure to perform and unpreparedness. The physical experience included signs and symptoms of ASCI that is important to recognise by first aiders, fellow teammates, coaches and referees. Lastly, participants described the emotional experience which has implications for all ASCI first responders.SignificanceAll rugby stakeholders, including players, first responders, coaches and referees, may gain valuable information from the experiences of players who have sustained these injuries. This information is also relevant for rugby safety initiatives in shaping education and awareness interventions.

Impairment Rating and Spinal Cord Injuries: Revisiting the Guides

2010 ◽  
Vol 15 (3) ◽  
pp. 1-7
Author(s):  
Richard T. Katz
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Functional Independence ◽  
Outcome Data ◽  
Multiple Organ ◽  
Loss Of Function ◽  
Sixth Edition ◽  
Organ Systems ◽  
Cord Injury ◽  
Impairment Ratings

Abstract This article addresses some criticisms of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) by comparing previously published outcome data from a group of complete spinal cord injury (SCI) persons with impairment ratings for a corresponding level of injury calculated using the AMA Guides, Sixth Edition. Results of the comparison show that impairment ratings using the sixth edition scale poorly with the level of impairments of activities of daily living (ADL) in SCI patients as assessed by the Functional Independence Measure (FIM) motor scale and the extended FIM motor scale. Because of the combinations of multiple impairments, the AMA Guides potentially overrates the impairment of paraplegics compared with that of quadriplegics. The use and applicability of the Combined Values formula should be further investigated, and complete loss of function of two upper extremities seems consistent with levels of quadriplegia using the SCI model. Some aspects of the AMA Guides contain inconsistencies. The concept of diminishing impairment values is not easily translated between specific losses of function per organ system and “overall” loss of ADLs involving multiple organ systems, and the notion of “catastrophic thresholds” involving multiple organ systems may support the understanding that variations in rating may exist in higher rating cases such as those that involve an SCI.

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