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

 

 

 

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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!

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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

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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.

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Spinal Modulation for Rehabilitation | Reggie Edgerton, PhD

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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

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Efforts underway to bring treatments to Australia

In this special 60 Minutes Report, Charles Wooley travels to Switzerland to watch something incredible – a paralyzed man walking. They’re faltering steps, but they signal a giant leap forward for science. And it is all part of a global effort involving the most brilliant doctors and the most courageous patients. It’s not a cure, but therapies along the way will help.

Dr. Courtine of Switzerland and Professor Bryce Vissel of Australia are interviewed about efforts toward bringing this technology to the paralyzed citizens of Australia.  Providing technology to the patients at a cost of 10 – 20 million would be less than the current annual SCI costs of 500 million in Australia.

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NervGen looking to use their technology to revolutionize nerve damage treatment

NervGen Pharma (CVE:NGEN) President and CEO Ernest Wong sat down with Steve Darling from Proactive Investors Vancouver to talk about the pharma company that has technology that hopes to regenerate nerve damage, that damage can be spinal cord or peripheral. Wong telling Proactive how the drug works and where it is in the pipeline and when NervGen hopes to get into a phase one clinical study.

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Enhancement of plasticity for functional recovery after spinal cord injury

Authors: S. F. IRVINE, S. GIGOUT, P. M. WARREN, J. C. F. KWOK

Lab Abstract:

To promote recovery after spinal cord injury (SCI), treatments aim to enhance regeneration of severed axons and the plasticity of surviving circuitry. Enzymatic removal of perineuronal nets (PNNs), a plasticity brake in the adult central nervous system (CNS), using intrathecal chondroitinase ABC (ChABC) injections successfully enhances plasticity and functional recovery, particularly in SCI models. PNNs envelop neuronal sub-populations throughout the CNS providing stabilisation of circuitry and thus regulation of plasticity. Whilst ChABC has proven beneficial to recovery alongside other treatments including rehabilitation, there are significant hurdles in regards to clinical application. This study aims to investigate an alternative method of PNN removal via non-invasive systemic PNN inhibition (PNNi) in combination with rehabilitation and its efficacy to enhance motor recovery after acute SCI. Firstly, as much of the PNN-associated neuronal populations are still relatively unknown in the spinal cord, we characterised normal PNN expression in the ventral motor pools using immunohistochemistry alongside specific motoneurone (Mn) markers. Compared to the acclaimed universal PNN marker Wisteria floribunda agglutinin lectin, the major PNN component aggrecan denoted significantly more PNNs around Mns. Selective Mn labelling revealed that PNNs encircled ~90% of alpha Mns, likely reflecting the population involved in the above mentioned motor recovery after SCI. To test the therapeutic efficacy of PNNi, adult female Lister Hooded rats received a moderate contusion to the T9 spinal cord and were assigned to treatment groups receiving PNNi or vehicle, with or without combination of rehabilitative treadmill training. Recovery was assessed using behavioural tests such as open field test hindlimb tests (BBB), horizontal ladder and von Frey assay. Preliminary results suggest that the systemic PNNi predominantly removes PNNs from the spinal cord, rather than the brain. Hindlimb motor functions were improved following rehabilitation. However, systemic plasticity enhancement seems to affect the forelimb function. Current experiments focus on defining the therapeutic window for optimal plasticity. Our data suggests that chronic PNNi application may provide a non-invasive strategy to enhance plasticity and regeneration after SCI.

*S. F. IRVINE1, S. GIGOUT1, P. M. WARREN1,2, J. C. F. KWOK1,3;
1Sch. of Biomed. Sciences, Fac. of Biol. Sci., Univ. of Leeds, Leeds, United Kingdom; 2Wolfston Ctr. for Age Related Dis., Kings Col. London, London, United Kingdom; 3Ctr. of Reconstructive Neurosciences, Inst. of Exptl. Med., The Czech Acad. of 7 Sci., Prague, Czech Republic. Enhancement of plasticity for functional recovery after spinal cord injury. Program No. 298.03. 2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2018. Online.

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University of Technology Sydney: Reviving Hope

New research into spinal cord injury and neurodegeneration is offering real hope of recovery for people with conditions long thought incurable.

For people living with the devastating effects of spinal cord injury or failing brain function, recovery has remained doubtful. But startling US research advances are now seeing movement and feeling restored to people with spinal cord injury.

UTS will build on this breakthrough research, alongside new research into causes and possible cures for Alzheimer’s and Parkinson’s disease through a new Centre for Neuroscience and Regenerative Medicine, currently being established.

In collaboration with SpinalCure Australia and Spinal Cord Injuries Australia, this not-to-be-missed lecture features world-renowned researcher, Professor Reggie Edgerton. It explores his astonishing new discoveries leading to unprecedented breakthroughs in recovery for patients with brain and spinal cord injury, and elaborates on plans for the continued development of his visionary work here in Sydney at UTS.

Renew your reason to hope, watch this fascinating lecture and lively expert panel forum and learn of exciting new research UTS is pursuing to preserve and improve quality of life. Watch the SpinalCure Australia Video Introduction

– Professor Bryce Vissel,

UTS Faculty of Science UTS Professor of Neuroscience Bryce Vissel will lead the University’s Centre for Neuroscience and Regenerative Medicine. Before joining UTS he led research for brain and spinal cord repair at the Garvan Institute of Medical Research and before that was based at the Salk Institute in the USA. Bryce is a regular media commentator on health matters, an advisor to government and patient advocacy groups, and has gained international recognition, receiving a number of awards including the prestigious Fulbright award, a Liebermann award and a BIOFIRST award. Special Guest Speaker

– Professor Reggie Edgerton,

University of California Reggie Edgerton has been teaching and conducting research at UCLA for more than 40 years. The milestones he has achieved in spinal cord regeneration have gained world-wide repute. His work focuses on how neural networks in the lumbar spinal cord of mammals, including humans, regain control of standing, stepping and voluntary control of fine movements after paralysis and how these motor functions can be modified by chronically imposing activity-dependent interventions after spinal cord injury. He is currently the Director of the Neuromuscular Research Laboratory and a Distinguished Professor of the Departments of Integrative Biology and Physiology, Neurobiology and Neurosurgery. Reggie received his Ph.D. in Exercise Physiology from Michigan State University, and Masters from University of Iowa and BS from East Carolina University.

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