scholarly journals Improving hindlimb locomotor function by Non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Benedikt Brommer ◽  
Miao He ◽  
Zicong Zhang ◽  
Zhiyun Yang ◽  
Jessica C. Page ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Crush Injury ◽  
Lumbar Spinal Cord ◽  
Locomotor Function ◽  
Adult Mice ◽  
Cord Injury ◽  
Spinal Segments ◽  
Blood Spinal Cord Barrier ◽  
Propriospinal Neurons

AbstractAfter complete spinal cord injuries (SCI), spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. However, it is unknown whether selective manipulation of these circuits can restore locomotor function in the absence of brain-derived inputs. By taking advantage of the compromised blood-spinal cord barrier following SCI, we optimized a set of procedures in which AAV9 vectors administered via the tail vein efficiently transduce neurons in lesion-adjacent spinal segments after a thoracic crush injury in adult mice. With this method, we used chemogenetic actuators to alter the excitability of propriospinal neurons in the thoracic cord of the adult mice with a complete thoracic crush injury. We showed that activating these thoracic neurons enables consistent and significant hindlimb stepping improvement, whereas direct manipulations of the neurons in the lumbar spinal cord led to muscle spasms without meaningful locomotion. Strikingly, manipulating either excitatory or inhibitory propriospinal neurons in the thoracic levels leads to distinct behavioural outcomes, with preferential effects on standing or stepping, two key elements of the locomotor function. These results demonstrate a strategy of engaging thoracic propriospinal neurons to improve hindlimb function and provide insights into optimizing neuromodulation-based strategies for treating SCI.

scholarly journals Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2025 ◽  
Author(s):  
Qinfeng Wu ◽  
Yana Cao ◽  
Chuanming Dong ◽  
Hongxing Wang ◽  
Qinghua Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Spinal Cord ◽  
Motor Function ◽  
Spinal Cord Injuries ◽  
Botulinum Toxin A ◽  
Treadmill Training ◽  
Lumbar Spinal Cord ◽  
Spinal Transection ◽  
Cord Injury ◽  
Lumbar Spinal

Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training retained hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery.

Spinal Cord Injury: Lessons from Locomotor Recovery and Axonal Regeneration in Lower Vertebrates

1998 ◽  
Vol 4 (4) ◽  
pp. 250-263 ◽  
Author(s):  
Andrew D. McClellan
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neural Development ◽  
Axonal Regeneration ◽  
Spinal Cord Injuries ◽  
Axonal Guidance ◽  
Behavioral Recovery ◽  
Locomotor Function ◽  
Cord Injury ◽  
Lower Vertebrates

After severe spinal cord injury in adult higher vertebrates (birds and mammals), there normally is little or no axonal regeneration and virtually no recovery of voluntary locomotor function below the lesion. In contrast, certain lower vertebrates, including lamprey, fish, and some amphibians, exhibit robust axonal regeneration and substantial recovery of locomotor function after spinal cord injury. The remarkable behavioral recovery of lower vertebrates with spinal cord injuries is due to at least three factors: 1) minimal hemorrhagic necrosis at the injury site and the lack of a neurite growth–inhibiting astrocytic scar, 2) an environment in the spinal cord that is permissive for axonal regeneration, and 3) mechanisms for directed axonal elongation and selection of appropriate postsynaptic targets. The latter two features probably represent developmental mechanisms for axonal guidance and synaptogenesis that persist in the nervous systems of these animals well beyond the main phase of neural development. In the injured spinal cords of higher vertebrates, the full complement of manipulations necessary to promote functional regeneration and behavioral recovery is unknown. An understanding of the mechanisms that result in repair of spinal cord injuries in lower vertebrates may provide guidelines for identifying the requirements for functional spinal cord regeneration in higher vertebrates, including humans.

scholarly journals Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat

2021 ◽  
Author(s):  
David SK Magnuson ◽  
Courtney T Shepard ◽  
Amanda M Pocratsky ◽  
Brandon L Brown ◽  
Morgan A Van Rijswijck ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Injury Severity ◽  
Dependent Manner ◽  
Thoracic Spinal Cord ◽  
Locomotor Function ◽  
Adult Rat ◽  
Thoracic Spinal ◽  
Cord Injury ◽  
Propriospinal Neurons

Long ascending propriospinal neurons (LAPNs) are a subpopulation of spinal cord interneurons that directly connect the lumbar and cervical enlargements. In uninjured animals, conditionally silencing LAPNs resulted in disrupted left-right coordination of the hindlimbs and forelimbs in a context-dependent manner, demonstrating that LAPNs secure alternation of the fore- and hindlimb pairs during overground stepping in the adult rat. Given their ventrolateral location in the spinal cord white matter, many LAPN axons likely remain intact following thoracic spinal cord injury (SCI), suggesting a potential role in the recovery of stepping. Thus, we hypothesized that silencing LAPNs after SCI would result in diminished hindlimb locomotor function. We found instead that silencing of spared LAPNs post-SCI restored the left-right hindlimb coordination associated with alternating gaits that was lost as a result of SCI. Several other fundamental characteristics of hindlimb stepping were also improved and the number of abnormal steps were reduced. However, hindlimb-forelimb coordination was not restored. These data suggest that the temporal information carried between the enlargements by the LAPNs after SCI may be detrimental to hindlimb locomotor function. These observations have implications for our understanding of the relationship between injury severity and functional outcome, for the efforts to develop neuro- and axo-protective therapeutic strategies, and also for the clinical study/implementation of spinal stimulation and neuromodulation.

scholarly journals Long-duration perforated patch recordings from spinal interneurons of adult mice

2011 ◽  
Vol 106 (5) ◽  
pp. 2783-2789 ◽  
Author(s):  
Andreas Husch ◽  
Nathan Cramer ◽  
Ronald M. Harris-Warrick
Keyword(s):  
Spinal Cord ◽  
Drug Application ◽  
Lumbar Spinal Cord ◽  
Spinal Cord Neurons ◽  
Perforated Patch ◽  
Adult Mice ◽  
Vital Functions ◽  
Cord Injury ◽  
Lumbar Spinal

It has been very difficult to record from interneurons in acute slices of the lumbar spinal cord from mice >3 wk of age. The low success rate and short recording times limit in vitro experimentation on mouse spinal networks to neonatal and early postnatal periods when locomotor networks are still developmentally immature. To overcome this limitation and enable investigation of mature locomotor network neurons, we have established a reliable procedure to record from spinal cord neurons in slices from adult, behaviorally mature mice of any age. Two key changes to the established neonate procedure were implemented. First, we remove the cord by a dorsal laminectomy from a deeply anesthetized animal. This enables respiration and other vital functions to continue up to the moment the maximally oxygenated lumbar spinal cord is removed, improving the health of the slices. Second, since adult spinal cord interneurons appear more sensitive to the intracellular dialysis that occurs during whole cell recordings, we introduced perforated patch recordings to the procedure. Stable recordings up to 12 h in duration were obtained with our new method. This will allow investigation of changes in mature neuronal properties in disease states or after spinal cord injury and allow prolonged recordings of responses to drug application that were previously impossible.

scholarly journals Effect of Seat Inclination on Seated Pressures of Individuals With Spinal Cord Injury

2004 ◽  
Vol 84 (3) ◽  
pp. 255-261 ◽  
Author(s):  
Christine L Maurer ◽  
Stephen Sprigle
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Injuries ◽  
Lumbar Spinal Cord ◽  
Total Force ◽  
Pressure Index ◽  
Cord Injury ◽  
Back Angle ◽  
Interface Pressures ◽  
Seat Inclination

Abstract Background and Purpose. Manual wheelchair configurations commonly include “squeezing” the wheelchair frame to improve balance for users with spinal cord injuries. This squeezing is achieved by lowering the rear portion of the seat relative to the front of the seat while maintaining the same back angle. The study's purpose was to examine the effect of increasing posterior seat inclination on buttock interface pressures. Subjects. Nine male and 5 female subjects (mean age=37 years, SD=11.2, range=19–55) with complete thoracic or lumbar spinal cord injury were tested. Methods. Subjects sat on a pressure mat placed over a foam cushion. Pressure readings were taken at seat angles reflecting seat height decreases of 0, 5.1, 7.6, and 10.2 cm (0, 2, 3, and 4 in) of the rear of the seat relative to the front of the seat. An analysis of variance and a Duncan multiple range test were used for data analysis. Results. No meaningful differences were found in measurements of interface pressure (dispersion index, contact area, and seat pressure index), total force on seat, or peak pressure index with posterior seat inclination. Discussion and Conclusion. The data indicate no meaningful evidence that squeezing a wheelchair frame increases seat interface pressures.

scholarly journals Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Courtney T Shepard ◽  
Amanda M Pocratsky ◽  
Brandon L Brown ◽  
Morgan A Van Rijswijck ◽  
Rachel M Zalla ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Dependent Manner ◽  
Thoracic Spinal Cord ◽  
Locomotor Function ◽  
Adult Rat ◽  
Thoracic Spinal ◽  
Cord Injury ◽  
Study Implementation ◽  
Propriospinal Neurons

Long ascending propriospinal neurons (LAPNs) are a subpopulation of spinal cord interneurons that directly connect the lumbar and cervical enlargements. Previously we showed, in uninjured animals, that conditionally silencing LAPNs disrupted left-right coordination of the hindlimbs and forelimbs in a context-dependent manner, demonstrating that LAPNs secure alternation of the fore- and hindlimb pairs during overground stepping. Given the ventrolateral location of LAPN axons in the spinal cord white matter, many likely remain intact following incomplete, contusive, thoracic spinal cord injury (SCI), suggesting a potential role in the recovery of stepping. Thus, we hypothesized that silencing LAPNs after SCI would disrupt recovered locomotion. Instead, we found that silencing spared LAPNs post-SCI improved locomotor function, including paw placement order and timing, and a decrease in the number of dorsal steps. Silencing also restored left-right hindlimb coordination and normalized spatiotemporal features of gait such as stance and swing time. However, hindlimb-forelimb coordination was not restored. These data indicate that the temporal information carried between the spinal enlargements by the spared LAPNs post-SCI is detrimental to recovered hindlimb locomotor function. These findings are an illustration of a post-SCI neuroanatomical-functional paradox and have implications for the development of neuronal- and axonal-protective therapeutic strategies and the clinical study/implementation of neuromodulation strategies.

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.

scholarly journals Dietary Supplementation for Para-Athletes: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2016
Author(s):  
Keely A. Shaw ◽  
Gordon A. Zello ◽  
Brian Bandy ◽  
Jongbum Ko ◽  
Leandy Bertrand ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dietary Supplements ◽  
Sports Medicine ◽  
Spinal Cord Injuries ◽  
Sport Performance ◽  
Future Research ◽  
Inclusion Criteria ◽  
Supplement Use ◽  
Sport Supplements ◽  
Cord Injury

The use of dietary supplements is high among athletes and non-athletes alike, as well as able-bodied individuals and those with impairments. However, evidence is lacking in the use of dietary supplements for sport performance in a para-athlete population (e.g., those training for the Paralympics or similar competition). Our objective was to examine the literature regarding evidence for various sport supplements in a para-athlete population. A comprehensive literature search was conducted using PubMed, SPORTDiscus, MedLine, and Rehabilitation and Sports Medicine Source. Fifteen studies met our inclusion criteria and were included in our review. Seven varieties of supplements were investigated in the studies reviewed, including caffeine, creatine, buffering agents, fish oil, leucine, and vitamin D. The evidence for each of these supplements remains inconclusive, with varying results between studies. Limitations of research in this area include the heterogeneity of the subjects within the population regarding functionality and impairment. Very few studies included individuals with impairments other than spinal cord injury. Overall, more research is needed to strengthen the evidence for or against supplement use in para-athletes. Future research is also recommended on performance in para-athlete populations with classifiable impairments other than spinal cord injuries.

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