scholarly journals Non-invasive approaches to functional recovery after spinal cord injury: Therapeutic targets and multimodal device interventions

2021 ◽  
Vol 339 ◽  
pp. 113612
Author(s):  
Claudio Pizzolato ◽  
Mehmet A. Gunduz ◽  
Dinesh Palipana ◽  
Jingnan Wu ◽  
Gary Grant ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Therapeutic Targets ◽  
Non Invasive ◽  
Cord Injury

scholarly journals Restoring Function After Severe Spinal Cord Injury Through Bioluminescence-Driven Optogenetics

2019 ◽  
Author(s):  
Eric D. Petersen ◽  
Erik D. Sharkey ◽  
Akash Pal ◽  
Lateef O. Shafau ◽  
Jessica R. Zenchak ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neuron ◽  
Functional Recovery ◽  
Rational Approach ◽  
Lumbar Spinal Cord ◽  
Locomotor Recovery ◽  
Non Invasive ◽  
Cord Injury ◽  
Neuronal Connections

The ability to manipulate specific neuronal populations of the spinal cord following spinal cord injury (SCI) could prove highly beneficial for rehabilitation in patients through maintaining and strengthening still existing neuronal connections and/or facilitating the formation of new connections. A non-invasive and highly specific approach to neuronal stimulation is bioluminescent-optogenetics (BL-OG), where genetically expressed light emitting luciferases are tethered to light sensitive channelrhodopsins (luminopsins, LMO); neurons are activated by the addition of the luciferase substrate coelenterazine (CTZ). This approach utilizes ion channels for current conduction while activating the channels through application of a small chemical compound, thus allowing non-invasive stimulation and recruitment of all targeted neurons. Rats were transduced in the lumbar spinal cord with AAV2/9 to express the excitatory LMO3 under control of a pan-neuronal or motor neuron-specific promoter. A day after contusion injury of the thoracic spine, rats received either CTZ or vehicle every other day for 2 weeks. Activation of either interneuron or motor neuron populations below the level of injury significantly improved locomotor recovery lasting beyond the time of stimulation. Utilizing histological and gene expression methods we identified neuronal plasticity as a likely mechanism underlying the functional recovery. These findings provide a foundation for a rational approach to spinal cord injury rehabilitation, thereby advancing approaches for functional recovery after SCI.

scholarly journals Non-invasive brain stimulation to promote motor and functional recovery following spinal cord injury

2017 ◽  
Vol 12 (12) ◽  
pp. 1933 ◽  
Author(s):  
Hatice Kumru ◽  
Aysegul Gunduz ◽  
John Rothwell ◽  
Joan Vidal
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Brain Stimulation ◽  
Non Invasive ◽  
Cord Injury

scholarly journals Corticospinal-motor neuronal plasticity promotes exercise-mediated recovery in humans with spinal cord injury

Brain ◽  
2020 ◽  
Vol 143 (5) ◽  
pp. 1368-1382 ◽  
Author(s):  
Hang Jin Jo ◽  
Monica A Perez
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Transcranial Magnetic Stimulation ◽  
Functional Recovery ◽  
Magnetic Stimulation ◽  
Primary Motor Cortex ◽  
Lumbar Spinal Cord ◽  
Non Invasive ◽  
Cord Injury ◽  
Stimulation Of

Abstract Rehabilitative exercise in humans with spinal cord injury aims to engage residual neural networks to improve functional recovery. We hypothesized that exercise combined with non-invasive stimulation targeting spinal synapses further promotes functional recovery. Twenty-five individuals with chronic incomplete cervical, thoracic, and lumbar spinal cord injury were randomly assigned to 10 sessions of exercise combined with paired corticospinal-motor neuronal stimulation (PCMS) or sham-PCMS. In an additional experiment, we tested the effect of PCMS without exercise in 13 individuals with spinal cord injury with similar characteristics. During PCMS, 180 pairs of stimuli were timed to have corticospinal volleys evoked by transcranial magnetic stimulation over the primary motor cortex arrive at corticospinal-motor neuronal synapses of upper- or lower-limb muscles (depending on the injury level), 1–2 ms before antidromic potentials were elicited in motor neurons by electrical stimulation of a peripheral nerve. Participants exercised for 45 min after all protocols. We found that the time to complete subcomponents of the Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) and the 10-m walk test decreased on average by 20% after all protocols. However, the amplitude of corticospinal responses elicited by transcranial magnetic stimulation and the magnitude of maximal voluntary contractions in targeted muscles increased on overage by 40–50% after PCMS combined or not with exercise but not after sham-PCMS combined with exercise. Notably, behavioural and physiological effects were preserved 6 months after the intervention in the group receiving exercise with PCMS but not in the group receiving exercise combined with sham-PCMS, suggesting that the stimulation contributed to preserve exercise gains. Our findings indicate that targeted non-invasive stimulation of spinal synapses might represent an effective strategy to facilitate exercise-mediated recovery in humans with different degrees of paralysis and levels of spinal cord injury.

scholarly journals Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury

2020 ◽  
Vol 11 ◽  
Author(s):  
Roxana Rodríguez-Barrera ◽  
Adrián Flores-Romero ◽  
Vinnitsa Buzoianu-Anguiano ◽  
Elisa Garcia ◽  
Karla Soria-Zavala ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Combination Strategy ◽  
Chronic Spinal Cord Injury ◽  
Cord Injury

Abstract #29: Scaling Spinal Cord injury Models for Non-invasive Stimulation

2019 ◽  
Vol 12 (2) ◽  
pp. e10-e11
Author(s):  
Dennis Q. Truong ◽  
Catherine Maglione ◽  
Yishai Valter ◽  
Louis Zannou ◽  
A. Duke Shereen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Non Invasive ◽  
Cord Injury ◽  
Injury Models

scholarly journals Exercise Ameliorates Spinal Cord Injury by Changing DNA Methylation

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 143
Author(s):  
Ganchimeg Davaa ◽  
Jin Young Hong ◽  
Tae Uk Kim ◽  
Seong Jae Lee ◽  
Seo Young Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Treadmill Exercise ◽  
Exercise Group ◽  
Control Group ◽  
Epigenetic Changes ◽  
Cord Injury ◽  
The Brain

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.

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