Survey responses needed to help with SCI priorities … Please take a moment

We have questions!!

Included here is a survey link (https://www.surveymonkey.com/r/MCPT5GM) asking you to rank areas of SCI related research – this will hopefully help us begin the brainstorming process to identify your interests or needs in terms of research and our abilities and resources to begin working on future research applications/grants.

Please feel free to share with other people who have experienced spinal cord injury, the more input the better.  After gathering as many responses as possible, we’ll use this to help guide further discussions about new research projects.

OSU Model Systems

Posted in Advocacy | Tagged

Putting 3D Printing to Work to Heal Spinal Cord Injury

“For people whose spinal cords are injured in traffic accidents, sports mishaps, or other traumatic events, cell-based treatments have emerged as a potential avenue for encouraging healing. Now, taking advantage of advances in 3D printing technology, researchers have created customized implants that may boost the power of cell-based therapies for repairing injured spinal cords.”

See the full article by Dr. Francis Collins in the NIH Directors Blog 

Posted in Biomaterials, Regenerative Medicine, spinal cord injury research, Stem Cell Research | Tagged | 1 Comment

Interfering with Semaphorin3A in perineuronal nets to enhance plasticity

Authors: D. CARULLI, R. BROERSEN, F. DE WINTER, H.-J. BOELE, B. HOBO, C. CANTO, E. M. MUIR, C. I. DE ZEEUW, J. VERHAAGEN

Daniela Carulli, visiting Professor with Verhaagen Lab Group

Lab Abstract:
Neuronal plasticity is crucial for our brain to learn, adapt to the environment and recover from brain injury. Plasticity decreases with age, particularly after childhood/adolescence. Perineuronal nets (PNNs) play a crucial role in restricting plasticity in the adult central nervous system. However, it is not entirely known how they act. PNNs are macromolecular assemblies of extracellular matrix and are composed of hyaluronan and chondroitin sulfate proteoglycans, which are kept together by link proteins and tenascin-R. We recently identified the chemorepulsive axon guidance protein Semaphorin3A (Sema3A) as a prominent component of PNN, suggesting that it may be a prime candidate in the control of PNN-mediated plasticity. To test this hypothesis we investigated the effect of interfering with Sema3A in the PNN of the deep cerebellar nuclei (DCN) of adult mice, at both the synaptic and behavioral level. Given that the DCN have abundant PNNs and are essential for associative eyeblink conditioning, they form a brain structure that is uniquely suited to investigate the role of PNN-associated Sema3A in learning-associated plasticity. To interfere with Sema3A signaling, we used an adeno-associated viral vector (AAV) encoding a soluble form of the Sema3A receptor component Neuropilin-1 (NP1-Y297A-Fc). NP1-Y297A-Fc retains its ability to interact with Sema3A, while binding with its other ligand, vascular endothelial growth factor (VEGF), is abolished by the mutation Y297A. With this approach, NP1-Y297A-Fc would act locally as a scavenger for Sema3A in the nets. We found that treatment with NP1-Y297A-Fc induces a significant increase in the size of axon terminals of Purkinje cells (the main inhibitory input on DCN neurons), which retain their discrete distribution along the target neuron membrane. In contrast, the digestion of the whole PNNs by the enzyme chondroitinase results in a decreased partition between neighboring Purkinje terminals. During associative motor learning, i.e. in mice subjected to eyeblink conditioning, PNNs and their Sema3A content in the DCN are reduced, suggesting that Sema3A plays an inhibitory role in the formation of this type of memory. Notably, digesting the whole PNNs in the DCN leads to faster learning in the eyeblink conditioning paradigm. These data show that PNNs are crucial for cerebellar plasticity and cerebellum-dependent learning, and support the hypothesis that the chemorepulsive axon guidance cue Sema3A is an effector protein with a key role in PNN-mediated plasticity.

Abstract Citation
D. CARULLI1,3, R. BROERSEN2,4, *F. DE WINTER1, H.-J. BOELE4, B. HOBO1, C. CANTO2,4, E. M. MUIR5, C. I. DE ZEEUW2,4, J. VERHAAGEN1;
1Lab. for Neuroregeneration, 2Lab. for Cerebellar Coordination and Cognition, Netherlands Inst. for Neurosci., Amsterdam, Netherlands; 3Dept. of Neurosci. and Neurosci. Inst. Cavalieri-Ottolenghi, Univ. of Turin, Turin, Italy; 4Dept. of Neurosci., Erasmus MC, Rotterdam, Netherlands; 5Dept. of Physiology, Develop. and Neurosci., Univ. of Cambridge, Cambridge, United Kingdom. Interfering with Semaphorin3A in perineuronal nets to enhance plasticity. Program No. 201.13. 2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2018. Online.

Posted in Chronic Spinal Cord Injury Research, Gene Therapy, Neuroscience Abstracts, Regenerative Medicine, spinal cord injury research | Tagged ,

Seeking Feedback on Research Priorities from SCI 2020

The spinal cord injury (SCI) research community has experienced great advances in discovery research, technology development, and promising clinical interventions in the past decade. To build upon these advances and maximize the benefit to persons with SCI, the NIH hosted a conference February 12-13, 2019 titled “SCI 2020: Launching a Decade of Disruption in Spinal Cord Injury Research”.

The NIH Institutes above are soliciting comments and suggestions on the top priorities identified in the five SCI 2020 breakout sessions as summarized below. The collated responses will be shared with the public and will be included in a meeting summary document prepared in collaboration with the Spinal Cord Injury Model Systems Knowledge Translation Center (https://msktc.org/about). The NIH Institutes encourage input from all interested stakeholders, including researchers, clinicians and health care providers, individuals with SCI, patient advocates and health advocacy organizations, scientific or professional organizations, federal agencies, as well as other interested members of the public. Responders to this RFI are also encouraged to provide input on how the research and research capacity building in the priority areas may be adopted in low resource settings including low- and middle-income countries. Organizations are strongly encouraged to submit a single response that reflects the views of their organization and membership.

Optional: Please indicate if you are a researcher, clinician or health care provider, individual with SCI, patient advocate, and/or other interested party. If you are submitting a response on behalf of an organization, please indicate the name of your organization.

LINK

 

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Strategies for Regeneration | Arthur Brown |

Dr. Brown will guide a discussion of how the brain is naturally able to recover from damage through the process of neuroplasticity – the ability to rewire circuits, so as to compensate for lost function. Further delving in to his research, Dr. Brown will discuss how the brain wires in the embryo have helped in developing a strategy to treat spinal cord injury and stroke. Dr. Arthur Brown has a long-standing interest in neurodevelopment and regeneration and has trained at the Samuel Lunenfeld Research Institute in Toronto and the Salk Institute in San Diego. He has made the conscious decision to combine his interests in neurodevelopment with spinal cord regeneration therapies.

“The body’s response to spinal cord injury includes processes that promote regeneration and processes that not only inhibit regeneration but actually increase damage.  The balance of these pro– and anti-regenerative forces determines the final clinical result.  We have three major areas of research focused on identifying and testing strategies to tip the balance of power away from damaging processes and towards productive healing.  Our research program includes anti-inflammatory strategies, cellular therapies and gene therapies designed to harness the good part of the body’s response to spinal cord injury while limiting the bad parts of this natural response to injury.

Regeneration in the nervous system is hindered by the expression of  genes that block nerve growth.  What regulates the activation of these inhibitory genes?

The absence of axonal regeneration after spinal cord injury has been attributed to nerve-repelling molecules in the damaged myelin and scar. These inhibitory molecules in the scar are produced by reactive astrocytes responding to the injury.  However, astrocytes have also been shown to produce molecules that promote nerve growth. We have identified a master control gene that regulates the balance between the anti- and pro-regenerative genes activated after spinal cord injury.  We are currently devising strategies to block this master control gene so as to maximize the expression of pro-regenerative genes and minimize the expression of anti-regenerative genes after spinal cord injury.”

McKillop WM1York EM2Rubinger L2Liu T2Ossowski NM3Xu K2Hryciw T2BrownA Conditional Sox9 ablation improves locomotor recovery after spinal cord injury by increasing reactive sprouting. (2016) Exp Neurology Sep

McKillop, M., Dragan, M., Pniak, A., Schedl, A. and Brown, A.  (2013). Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury.  Glia, 61(2):164-177.

Robarts Research

 

 

 

Posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Regenerative Medicine, spinal cord injury research | Tagged ,

CPAR: Joel Burdick from Caltech on Epidural Spinal Stimulation

In this video, Joel Burdick peels back the work and strategies that go into making the best algorithms for spinal cord injury stimulation and recovery.  This is a must see!

Posted in Chronic Spinal Cord Injury Research, Neuromodulation, Rehabilitation, spinal cord injury research | Tagged ,

What does “Disruptive” mean? Thoughts on the NIH SCI 2020 meeting

Neural Regeneration Research Article:

Read the perspective from a SCI Researcher’s point of view:  

On September 12 and 13, 2019, the National Institute of Neurological Disorders and Stroke (NINDS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), as well as other federal agencies and several private foundations sponsored a stake holder meeting at the National Institutes of Health (NIH) Bethesda campus with a provocative title: “SCI 2020: Launching a decade for disruption in spinal cord injury research”. Over the past decade, “disruptive” has become a cool buzz word for entrepreneurs to use to market their technology. In this context, disruptive means “innovative, ingenious, and unconventional” (typically definition #2 in online dictionaries). The hope is their new technology or business model is so powerful it will upend current technologies and come to dominate the market place.  Uber’s destruction of taxi companies worldwide is a leading example of being “disruptive”.

Read the Full Article:  Lemmon VP. What does “Disruptive” mean? Thoughts on the NIH SCI 2020 meetingNeural Regen Res [serial online] 2019 [cited 2019 May 11];14:1527-9.

Available from: http://www.nrronline.org/text.asp?2019/14/9/1527/255969

Posted in Advocacy, spinal cord injury research | Tagged ,

Combined administration of electro-magnetic stimulation (EMS) at spinal level and at leg muscles to modulate neurophysiological properties at spino-muscular circuitry in healthy and SCI humans

Authors: V. L. ARVANIAN, H. A. PETROSYAN, A. TESFA, M. FAHMY, C. ZOU, S. SISTO

Victor Arvanian

Lab Abstract:

H-reflex is recognized as an important neurophysiology tool used in evaluation of spino-muscular circuitry. H-reflex is sensitive to conditions and activity. For example, H-reflex diminishes after several days in zero gravity and is modulated differently depending on muscle activity. Spinal cord injury (SCI) reportedly affects threshold intensity and frequency dependent depression (FDD) of H-reflex. We examined 4 healthy and 3 SCI participants; study was approved by the IRB and conducted in accordance with the Declaration of Helsinki. We measured soleus M-wave and H- reflex recruitment curves using peripheral tibial nerve stimulation after each following condition: (i) baseline, (ii) initial 25 min session of EMS over spinal L5 level (SEMS; 0.2 Hz frequency, 70% coil intensity), (iii) additional 15 min session of SEMS, (iv) 15-min session of EMS at leg muscles. FDD of H-reflex (stim current was set to evoke 40% of H-max, using 0.2, 1, 2 and 5 Hz stim rate) was examined after taking baseline measures and then after end of muscle stimulation. Baseline measurements (prior SEMS] ) revealed a less steep (flatter) rise phase and more prolonged plateau of the recruitment curve of H-reflex, as well as a lesser depression rate of FDD in SCI vs healthy participants. In both healthy and SCI subjects, 1stapplication of SEMS for 25mins induced substantial facilitation of both M-response and H-reflex; this associated with a significant leftward shift of the recruitment curves for M- and H-responses and a marked decrease in the threshold currents to evoke H- and M-responses. 2nd follow-up application of SEMS for 15 min did not induce further changes, thus indicating that effects of SEMS reached its maximum after initial 1st 25 min of SEMS. However, EMS application over leg muscles induced further facilitation of M-wave and H-response. These results suggest that EMS over spinal level and leg muscles exert their effects on H-reflex through different mechanisms. Results also revealed improvement of FDD rate following SEMS/leg stimulation in SCI participants. Importantly, one SCI participant was engaged in 20 min exercise training sessions (NUSTEP exercise machine) after completion of SEMS/leg stimulation protocols; after 5 sessions the subject, who is 12 years post SCI, reported an increase in sensation and function for the first time. It is important to note that this subject had been performing similar exercise on a regular basis prior to this study without functional changes. Results suggest that spinal/leg EMS stimulation combined with exercise may be a potential approach in clinics for a variety of spinal or peripheral nerve conditions.

*V. L. ARVANIAN1, H. A. PETROSYAN1, A. TESFA1, M. FAHMY1, C. ZOU2, S. SISTO3;
1Res. Services, Northport VAMC, Northport, NY; 2StonyBrook Univ., Stony Brook, NY; 3Univ. of Buffalo, Buffalo, NY. Combined administration of electro-magnetic stimulation (EMS) at spinal level and at leg muscles to modulate neurophysiological properties at spino-muscular circuitry in healthy and SCI humans. Program No. 298.12. 2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2018. Online.

Posted in Chronic Spinal Cord Injury Research, Neuromodulation, Neuroscience Abstracts, Rehabilitation, spinal cord injury research | Tagged , | 1 Comment

Spinal Modulation for Rehabilitation | Reggie Edgerton, PhD

Posted in Chronic Spinal Cord Injury Research, Neuromodulation, Rehabilitation, spinal cord injury research | Tagged ,

Spinal Neuromodulation for Motor Control and Beyond | Daniel Lu. MD, PhD

Nature.com  A Proof-of-Concept Study of Transcutaneous Magnetic Spinal Cord Stimulation for Neurogenic Bladder

Posted in Chronic Spinal Cord Injury Research, Neuromodulation, Rehabilitation, spinal cord injury research | Tagged ,