Tag Archives: #spinalcordinjury

Autologous Adipose Injection For Shoulder Pain in Wheelchair Users With Spinal Cord Injury (Medicine)

A team of specialists in regenerative rehabilitation conducted a successful pilot study investigating micro-fragmented adipose tissue (MFAT) injection for rotator cuff disease in wheelchair users with spinal cord injury. They demonstrated that MFAT injection has lasting pain-relief effects. The article, “A pilot study to evaluate micro-fragmented adipose tissue injection under ultrasound guidance for the treatment of refractory rotator cuff disease in wheelchair users with spinal cord injury,” (doi: 10.1080/10790268.2021.1903140) was published ahead of print on April 8, 2021, by The Journal of Spinal Cord Medicine.

The authors are Trevor Dyson-Hudson, MD , and Nathan Hogaboom, PhD , at Kessler Foundation; and Gerard Malanga, MD, a founder of the New Jersey Regenerative Institute and visiting scientist at Kessler Foundation, and Chris Cherian, MD, of Rutgers New Jersey Medical School. The study was conducted at the Derfner-Lieberman Laboratory for Regenerative Rehabilitation Research in the Center for Spinal Cord Injury Research at Kessler Foundation.

Shoulder pain is a common occurrence among wheelchair users with spinal cord injury because they rely solely on their upper limbs to perform everyday tasks. Often, pain is caused by soft-tissue injuries such as damage to rotator cuff tendons. Many non-surgical therapies for shoulder pain exist, including pain medication, physical therapy, and equipment modifications, but these have shown limited efficacy. Persistent shoulder pain can significantly lessen quality of life, and if conservative therapies fail, shoulder surgery is frequently the only option, which comes with its own set of risks and potential setbacks.

Dr. Malanga (right) and Dr. Dyson-Hudson (center) conduct follow up ultrasound examination on study participant. © Kessler Foundation

In this single-group pilot study, researchers explored the efficacy of a minimally invasive biological intervention involving an ultrasound-guided injection of MFAT, which harbors a potential source of bioactive and regenerative components for orthopedic conditions and may provide cushioning that can improve function and alleviate pain caused by rotator cuff injuries.

Ten wheelchair users with chronic spinal cord injury who had moderate-to-severe shoulder pain for more than six months caused by refractory rotator cuff disease participated in the study. All received an injection of MFAT and were evaluated at six and 12 months after treatment. Evaluation metrics included the 11-point Numerical Rating Scale, the Wheelchair User’s Shoulder Pain Index, Brief Pain Inventory pain interference items (BPI-17), Patient Global Impression of Change, ultrasound and physical examinations, and adverse events.

The results were encouraging, according to Drs. Hogaboom and Dyson-Hudson, co-directors of the Derfner-Lieberman Laboratory. Nearly 80 percent saw a meaningful decrease in pain symptoms, and all but one reported some improvement in pain and function. Moreover, scores declined steadily over the first three months for all metrics, and over the entire year for the BPI-17 metric, suggesting that this intervention has long-lasting effects. There were no significant adverse events.

“These results show that the minimally invasive injection of micro-fragmented adipose tissue is a safe and efficacious option for wheelchair users with shoulder pain caused by rotator cuff disease,” said Dr. Malanga. “Based on the success of our study, a randomized controlled study with a larger number of subjects has been initiated in this patient population through funding from the New Jersey Commission for Spinal Cord Research. We feel there is great potential for this therapy to help people with shoulder pain manage their symptoms and improve their quality of life. We credit our success to the Derfner Foundation for providing the initial funding to pursue this promising intervention, and acknowledge the ongoing efforts of the Alliance for Regenerative Rehabilitation Research & Training to advance the fields of rehabilitation sciences and regenerative medicine.”

Funding sources: Financial support was received in the form of a Pilot Grant and Fellowship Grant from the Derfner Foundation to conduct this pilot study. This research received funding from the Alliance for Regenerative Rehabilitation Research & Training (AR3T), which is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Neurological Disorders and Stroke (NINDS), and National Institute of Biomedical Imaging and Bioengineering (NIBIB) of the National Institutes of Health under Award Number P2CHD086843.

Featured image: Pilot study of micro-fragmented adipose tissue injection suggests that the biologic is an effective treatment option for wheelchair users with chronic shoulder pain © Kessler Foundation

Reference: Nathan Hogaboom, Gerard Malanga, Chris Cherian & Trevor Dyson-Hudson (2021) A pilot study to evaluate micro-fragmented adipose tissue injection under ultrasound guidance for the treatment of refractory rotator cuff disease in wheelchair users with spinal cord injury, The Journal of Spinal Cord Medicine, DOI: 10.1080/10790268.2021.1903140

Provided by Kessler Foundation

About Kessler Foundation:

Kessler Foundation, a major nonprofit organization in the field of disability, is a global leader in rehabilitation research that improves cognition, mobility and long-term outcomes, including employment, for people with neurological disabilities caused by diseases and injuries of the brain and spinal cord. Kessler Foundation leads the nation in funding innovative programs that expand opportunities for employment for people with disabilities. Learn more by visiting http://www.KesslerFoundation.org

Search for Biomarkers of Injury Severity to Assist Patients With Spinal Cord Trauma (Medicine)

A continuation of ongoing effort by Kazan Federal University and its partners saw light in Brain Sciences.

The research is conducted by Kazan University’s Open Lab Gene and Cell Technologies (Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology) and Republic Clinical Hospital of Kazan. Lead Research Associate Yana Mukhamedshina serves as project head.

Spinal cord injury mechanisms include primary and secondary injury factors. Primary injury is mechanical damage to the nervous tissue and vasculature with immediate cell death and hemorrhage. Secondary damage leads to significant destructive changes in the nervous tissue due to the development of excitotoxicity, death of neurons and glial cells, inflammatory reactions, and the formation of a glial scar, which prevents the restoration of nerve connections. It should be noted that secondary trauma during this period leads to more serious clinical consequences than the original primary trauma. In this regard, there is an urgent need to develop a panel of diagnostic biomarkers to determine the severity of injury. Therefore, over the past two decades, there has been a growing interest in the development of new, reliable and practical tools for diagnosing the degree of spinal cord injury and predicting the outcome of the disease.

This paper demonstrates the importance of measuring serum cytokine concentrations as a quick and affordable means of accurately classifying the severity of spinal cord injury in patients, eliminating the risks and complications associated with the use of repeated cerebrospinal fluid sampling. But more research is needed to integrate those findings into the universal standard of care for spinal cord injury screening and diagnosis.

The need for predictive biomarkers is multifaceted. First, health care decisions will become more personalized and tailored to each case, which will minimize ineffective interventions and facilitate patient follow-up. Second, such tools would be useful in the provision of medical care for patients with spinal cord injury in developing countries that lack modern medical resources. Third, it will significantly accelerate research into spinal cord injury at both the preclinical and clinical levels.

Results will allow the development of a test system for assessing the prognostic course of traumatic spinal cord injury, as well as recommendations and suggestions for the use of the most effective therapy option. They will also contribute to the development of new early biomarkers of neurodegenerative diseases.

Featured image: The research is conducted by Kazan University’s Open Lab Gene and Cell Technologies (Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology) and Republic Clinical Hospital of Kazan. Lead Research Associate Yana Mukhamedshina serves as project head. © Kazan Federal University

Reference: Ogurcov, S.; Shulman, I.; Garanina, E.; Sabirov, D.; Baichurina, I.; Kuznetcov, M.; Masgutova, G.; Kostennikov, A.; Rizvanov, A.; James, V.; Mukhamedshina, Y. Blood Serum Cytokines in Patients with Subacute Spinal Cord Injury: A Pilot Study to Search for Biomarkers of Injury Severity. Brain Sci. 2021, 11, 322. https://doi.org/10.3390/brainsci11030322 https://www.mdpi.com/2076-3425/11/3/322

Provided by Kazan Federal University

Tadpole Nerve Regeneration Capacity Provides Clue to Treating Spinal Cord Injury (Medicine)

Nagoya University researchers have identified a gene that plays a crucial role in regenerating neurons of African clawed frog tadpoles, which has an unusually high capacity for nerve regeneration. Their study, recently published in the journal iScience, showed that introducing the gene into mice with spinal cord injury (SCI) led to a partial recovery of their lost motor functions. These findings could contribute to the development of a new therapy for SCI, which often causes a person to experience permanent and severe physical and neurological disabilities.

Repairing spinal cord injuries in humans and other mammals is difficult, partly because of their limited ability to repair and regenerate neural tissues in the spinal cord. In contrast, there are animals with a high capacity for nerve regeneration, such as the African clawed frog. “As a tadpole, it is fully capable of functional recovery after a spinal cord injury,” said Drs. Dasfne Lee-Liu and Juan Larrain from the P. Universidad Catolica de Chile in their study, “Genome-wide expression profile of the response to spinal cord injury in Xenopus laevis reveals extensive differences between regenerative and non-regenerative stages,” published in 2014.

In this context, the Nagoya University research team conducted a collaborative study with Drs. Lee-Liu and Larrain to identify transcription factors that regulate nerve regeneration in the African clawed frog tadpole, with the aim of inducing regenerative effects in mammals. The team comprehensively analyzed the gene expression profiles of tadpoles in response to SCI, and found that a gene called Neurod4 was expressed predominantly during nerve regeneration. The team thus hypothesized that this gene is a key factor in the regeneration of neural tissues after an injury.

In this study, the team also focused on the fact that in mammals, neural stem cells (known as self-renewing cells) derived from the ependymal cells lining the central canal of the spinal cord are activated and proliferate in the early stage of SCI, although these types of neural stem cells eventually transform into astrocytes — a type of cell that forms rigid glial scars.

“Taking these things together, we thought that introducing Neurod4 into activated neural stem cells may help regenerate neurons,” said Associate Professor Atsushi Natsume of the Nagoya University Graduate School of Medicine, the corresponding author of the study.

To that end, the team conducted experiments in which the Neurod4 gene was introduced to activated neural stem cells in mice just after SCI. The researchers observed that the neural stem cells were successfully converted into neurons and, interestingly, the mice occasionally moved their paralyzed hind legs. Dr. Natsume explained, “Neurod4 introduced into activated neural stem cells facilitates the production of relay neurons, which project to motor neurons of the hind legs. As a secondary effect, glial scar formation was suppressed after the subacute phase of spinal cord injury. This effect allows an environment that was conducive for axons to elongate beyond the injury site and form synapses, thereby improving the motor function of the hind legs.”

“Our method is to introduce a neuro regenerative gene directly into neural stem cells that are already present in the spinal cord. This could lessen the problems of rejection and tumor formation, which often occur in conventional stem cell transplantation methods. We believe this study will contribute to the development of new therapeutic approaches to spinal cord injury,” he added.

The study, “Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury,” was published in the journal iScience on January 20, 2021 at DOI: 10.1016/j.isci.2021.102074.

Authors: Toshiki Fukuoka, Akira Kato, Masaki Hirano, Fumiharu Ohka, Kosuke Aoki, Takayuki Awaya, Alimu Adilijiang, Sachi Maeda, Kuniaki Tanahashi, Junya Yamaguchi, Kazuya Motomura, Hiroyuki Shimizu, Yoshitaka Nagashima, Ryo Ando, Toshihiko Wakabayashi, Dasfne Lee-Liu, Juan Larrain, Yusuke Nishimura, Atsushi Natsume

Featured image: Introducing Neurod4 into neural stem cells derived from ependymal cells in mice just after spinal cord injury promotes neuronal differentiation. The differentiated neurons form synapses, which leads to an improvement in the motor function of their hind legs. © Atsushi Natsume

Provided by Nagoya University

Injectable Porous Scaffolds Promote Better, Quicker Healing After Spinal Cord Injuries (Medicine)

Hydrogel scaffolds with regularly spaced pores encourage spinal cords cells to grow, improve regeneration of nerve cells.

Spinal cord injuries can be life-changing and alter many important neurological functions. Unfortunately, clinicians have relatively few tools to help patients regain lost functions.

In APL Bioengineering, by AIP Publishing, researchers from UCLA have developed materials that can interface with an injured spinal cord and provide a scaffolding to facilitate healing. To do this, scaffolding materials need to mimic the natural spinal cord tissue, so they can be readily populated by native cells in the spinal cord, essentially filling in gaps left by injury.

“In this study, we demonstrate that incorporating a regular network of pores throughout these materials, where pores are sized similarly to normal cells, increases infiltration of cells from spinal cord tissue into the material implant and improves regeneration of nerves throughout the injured area,” said author Stephanie Seidlits.

The researchers show how the pores improve efficiency of gene therapies administered locally to the injured tissues, which can further promote tissue regeneration.

Since many spinal cord injuries result from a contusion, the biomaterial implants need to be injected in or near the injured area without causing damage to any surrounding spared tissue. A major technical challenge has been fabricating scaffold materials with cell-scale pore sizes that are also injectable.

In the researchers’ method, they injected beads of material through a small needle into the spinal cord, where the beads stick together to form a scaffold, where cells can crawl in the pore spaces between the beads. The researchers found inclusion of these larger cell-scale pores within biomaterial scaffolds improved cell infiltration, gene delivery, and tissue repair after spinal cord injury, compared to more conventional materials with nanoscale pores.

The researchers made the highly porous scaffolds using two different methods. One was simpler but created a more irregularly sized pore network. The second was more complicated but created a highly regular pore structure.

Even though both materials had the same average pore size and chemical composition, more regenerating nerves were found to infiltrate scaffolds with regularly shaped pores.

“These results inform how to maximize interfacing with the nervous system,” said Seidlits. “This has potential applications not only for developing new therapies for brain and spinal cord repair but also for brain-machine interfaces, prosthetics, and treatment of neurodegenerative diseases.”

The article “Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord” is authored by Arshia Ehsanipour, Mayilone Sathialingam, Laila M. Rad, Joseph de Rutte, Rebecca D. Bierman, Jesse Liang, Weikun Xiao, Dino Di Carlo, and Stephanie K. Seidlits. The article will appear in APL Bioengineering on Mar. 9, 2021 (DOI: 10.1063/5.0035291). After that date, it can be accessed at https://aip.scitation.org/doi/10.1063/5.0035291.

Featured image: Images show myelinated axons in biomaterial scaffolds eight weeks after injection into the injured cord of a mouse. Scaffolds were fabricated from hyaluronic acid (HA) with a regular network of cell-scale macropores and loaded with gene therapy vectors encoding for brain-derived neurotrophic factor (BDNF), to promote axonal survival and regeneration. These were compared to control scaffolds, which were lacking the BDNF vector. Images show dense infiltration of cells (shown in blue, cell nuclei), axons (shown in red in A, NF200 protein) and myelinating glial cells (shown in green, myelin basic protein) in the BDNF-laden scaffolds. Scale bars = 200 μm. © Seidlits et al.

Provided by American Institute of Physics

New Treatment Helps Patients With a Spinal Cord Injury (Medicine)

Spinal cord injuries disrupt the mechanism by which our bodies regulate blood pressure. A team of Swiss and Canadian scientists have developed a treatment that allows patients to regain control of their blood pressure, using targeted electrical spinal-cord stimulation. No medication is required. The team’s findings were published today in Nature.

An international team of scientists headed by Grégoire Courtine at EPFL and CHUV and Aaron Phillips at the University of Calgary has developed a treatment that can dramatically improve the lives of patients with a spinal cord injury.

“A serious and underrecognized result of these injuries is unstable blood pressure, which can have devastating consequences that reduce quality of life and are life threatening. Unfortunately, there are no effective therapies for unstable blood pressure after spinal cord injury”. said Dr. Aaron Phillips, co-lead author of the study (see affiliations below). “We created the first platform to understand the mechanisms underlying blood pressure instability after spinal cord injury.”

Their findings, published today in Nature, builds on research that has already enabled several paraplegics to walk again through epidural electrical stimulation (EES). But instead of targeting the region of the spinal cord that produces leg movements, they delivered EES in the region containing the neural circuits that regulate blood pressure. In addition, they adapted the stimulation protocol in real-time based on measurements taken by a blood-pressure monitor implanted in an artery. The monitor measures blood pressure continuously, and adapts the instructions sent to a pacemaker that in turn delivers electrical pulses over the spinal cord. The stimulation is biomimetic, since it recapitulates the natural activation of the body’s hemodynamic system. “The stimulation compensates for the broken communication line between the patient’s central nervous system and sympathetic nervous system,” says Courtine.

The research team initially tested their method in preclinical rodent and nonhuman primate models in order to understand the mechanisms that disrupt blood pressure modulation after spinal cord injury, and to identify where and how the stimulation patterns should be applied to obtain the desired hemodynamic responses. Jocelyne Bloch, the neurosurgeon who heads the .NeuroRestore research center with Courtine and who carried out the surgical implants, was surprised at how quickly the stimulation protocol worked. “It was impressive to see the blood pressure rise to the target level immediately after the stimulation was applied,” she says.

The electrical stimulation treatment provided a huge relief – much more effective than medication.

— Richdeep Gill, first patient

After these initial tests, the scientists tried their method on a human patient.

“I suffered from daily episodes of low blood pressure, especially in the morning and evening,” says Richi, 38 years old. “But since I’ve had the implant, it happens much less often – maybe once every couple of weeks.” Himself a surgeon, Richi lost the use of all four limbs after a sport accident. “Those daily episodes of hypotension were a real burden. They also disturbed my vision and prevented me from performing even simple everyday tasks. The electrical stimulation treatment provided a huge relief – much more effective than medication.”

One of the physicians working with Richi, Dr. Sean Dukelow, states: “Since using this system, Richi was able to completely stop all drugs he was using to manage blood pressure instability. This has been transformative, and over the long-term may reduce Richi’s risk of cardiovascular disease.”
The team intends to continue its research thanks to a large grant received from the US Defense Advanced Research Projects Agency (DARPA). At the same time, Onward (formerly GTX Medical) – a startup based at EPFL Innovation Park and in the Netherlands – will develop and market clinical devices based on the team’s discoveries.

Image credit: © 2021 EPFL Mediacom Communication visuelle

Reference: Jordan W. Squair, Matthieu Gautier, Lois Mahe, Jan Elaine Soriano, Andreas Rowald, Arnaud Bichat, Newton Cho, Mark A. Anderson, Nicholas D. James, Jerome Gandar, Anthony V. Incognito, Giuseppe Schiavone, Zoe K. Sarafis, Achilleas Laskaratos, Kay Bartholdi, Robin Demesmaeker, Salif Komi, Charlotte Moerman, Bita Vaseghi, Berkeley Scott, Ryan Rosentreter, Claudia Kathe, Jimmy Ravier, Laura McCracken, Xiaoyang Kang, Nicolas Vachicouras, Florian Fallegger, Ileana Jelescu, YunLong Cheng, Qin Li, Rik Buschman, Nicolas Buse, Tim Denison, Sean Dukelow, Rebecca Charbonneau, Ian Rigby, Steven K. Boyd, Philip J. Millar, Eduardo Martin Moraud, Marco Capogrosso, Fabien B. Wagner, Quentin Barraud, Erwan Bezard, Stéphanie P. Lacour, Jocelyne Bloch, Grégoire Courtine & Aaron A. Phillips, ‘Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury’. Nature, January 27th, 2021, DOI 10.1038/s41586-020-03180-w https://www.nature.com/articles/s41586-020-03180-w

Provided by EPFL

Research Finds Blood Pressure Can be Controlled Without Drugs After Spinal Cord Injury (Medicine)

Dr. Richi Gill, MD, is back at work, able to enjoy time with his family in the evening and get a good night’s sleep, thanks to research. Three years ago, Gill broke his neck in a boogie board accident while on vacation with his young family. Getting mobile again with the use of a wheelchair is the first thing, Gill says, most people notice. However, for those with a spinal cord injury (SCI), what is happening inside the body also severely affects their quality of life.

“What many people don’t realize is that a spinal cord injury prevents some systems within the body from regulating automatically,” says the 41-year-old. “My blood pressure would drop drastically, leaving me fatigued, dizzy, and unable to focus. The condition can be life threatening, requiring medication for life.”

Dr. Aaron Phillips, PhD, at the University of Calgary’s Cumming School of Medicine (CSM) and Grégoire Courtine, PhD, at Swiss Federal Institute of Technology (EPFL) , co-led an international study which has shown that spinal cord stimulators can bridge the body’s autonomous regulation system, controlling blood pressure without medication. Findings are published in Nature.

For people with SCI, the discovery is life changing, “The spinal cord acts as a communication line allowing the brain to send signals to tell the body such as when and how to move, as well as how to control vital functions, including blood pressure,” says Phillips, co-principal investigator and assistant professor at the CSM. “This communication line is broken after a spinal cord injury. We created the first platform to understand the mechanisms underlying blood pressure instability after spinal cord injury, which allowed us to develop a new cutting-edge solution.”

Gill is the first study participant in a series of clinical trials planned for Calgary and Switzerland. “We are going to collaborate with a company called Onward to develop a neurostimulation system dedicated to the management of blood pressure in people with spinal cord injury,” says Courtine, co-principal investigator and professor at the EPFL.

In the study, targeted epidural electrical stimulation (EES) of the spinal cord was used to stabilize hemodynamics (blood flow throughout the body) allowing for vital organs to maintain an appropriate supply of blood. The researchers discovered the exact placement on the spine for their stimulator, and the circuitry of the sympathetic nervous system underlying blood pressure control. This new knowledge allowed for the development of a neuroprosthetic closed-loop communication system, to replace lost hemodynamic control.

“We are really excited that people with spinal cord injury are able to stop their blood pressure medication and get back to enjoying a full daily routine with improved blood flow to their brain and organs,” says Dr. Sean Dukelow, MD, PhD, clinician scientist at the CSM and author on the study. “People feel more alert, are able to be upright and in their wheelchair without losing consciousness, and over the long-term we think this will reduce the risk of heart disease and stroke.”

“It’s exciting to see the science help push things forward,” says Gill. “I’m excited that Calgary will be one of the sites for a clinical trial. Research made a positive effect on my life and I’m glad others will benefit, too.”

Gill continues to work as part of the Calgary Adult Bariatric Surgery Clinic and is now the Director of the Alberta Obesity Centre.

Reference: Squair, J.W., Gautier, M., Mahe, L. et al. Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury. Nature (2021). https://www.nature.com/articles/s41586-020-03180-w https://doi.org/10.1038/s41586-020-03180-w

Provided by University of Calgary

Mouse Study: Gabapentin Prevents Harmful Structural Changes In Spinal Cord (Medicine)

Research led by The Ohio State University Wexner Medical Center and College of Medicine found that the widely prescribed pain-relief drug gabapentin can prevent harmful structural changes in the injured spinal cords of mice, and also block cardiovascular changes and immune suppression caused by spinal cord injury.  

“Gabapentin is often prescribed as a treatment for pain, but if it is given early after injury – before symptoms develop – it can also limit structural changes in nerve cells. We show that these benefits remain even one month after stopping gabapentin treatment in spinal injured mice. We believe that gabapentin could be repurposed as a prophylactic therapy that can prevent autonomic dysfunction in people affected by spinal cord injuries,” said Phillip Popovich, senior author and chair of Ohio State’s Department of Neuroscience.  

Study findings are published online in the journal Cell Reports. 

“This is the first time a treatment has been shown to prevent the development of autonomic dysfunction, rather than manage the symptoms caused by autonomic dysfunction. In response to stress or danger, autonomic nerve cells in the spinal cord trigger a ‘fight or flight’ response. This is a normal and helpful response that increases blood pressure and releases hormones like adrenaline and cortisol,” said lead author Faith Brennan, research scientist in Ohio State’s department of neuroscience. 

But, after traumatic spinal cord injury, massive structural changes occur within spinal autonomic nerve centers that control the fight or flight response, and these changes cause uncontrolled autonomic reflexes. 

For example, normally harmless stimuli, such as the bladder filling, will trigger the fight or flight response. But because of the spinal cord injury, the response is uncontrolled and can cause several health problems, including severe high blood pressure, heart rate slowing and long-term immune suppression. 

“Autonomic dysfunction is a major problem for people living with a spinal cord injury. The cardiovascular complications can lead to severe morbidities like heart attack and stroke while long-term immune suppression can lead to serious recurrent infections like pneumonia,” Popovich said. Currently, these symptoms can only be managed, (regular bowel/bladder voiding regimens, for example), but there is no treatment.  

“The possibility of repurposing gabapentin as a prophylactic therapy to prevent the development of autonomic dysfunction could significantly improve the quality of life for individuals living with spinal cord injuries, including greater independence in society, reduced caregiver reliance, reduced infection susceptibility and increased life expectancy,” Brennan said. “Gabapentin is FDA-approved, and is already widely used to manage neuropathic pain caused by spinal cord injuries. If patients are treated early after their injuries, gabapentin could prevent the harmful structural changes that are inevitable in most severe spinal cord injuries.” 

This study builds on Ohio State’s previous research showing that autonomic dysfunction directly drives immune suppression, said Popovich, who also is a researcher in Ohio State’s Neurological Institute and the Belford Center for Spinal Cord Injury.   

“We don’t know how long treatment can be delayed after injury and still maintain the beneficial effects. Ongoing studies in the Belford Center are optimizing this treatment onset window. We also don’t know if gabapentin targets other cells/organs in the body, so we’ll investigate the effects of this therapy on other tissues beyond the spinal cord,” Popovich said.  

The Ohio State team collaborated with scientists at Duke University and University of California San Francisco on this study. 

This research is supported by the U.S. Department of Defense, the Craig H. Neilsen Foundation, Wings for Life, The National Institutes of Health, the Ray W. Poppleton Endowment and the Ohio Department of Higher Education. 

Featured image: Phillip Popovich is a professor and chair of Ohio State’s Department of Neuroscience and Executive Director of the Belford Center for Spinal Cord Injury at The Ohio State University College of Medicine. © The Ohio State University Wexner Medical Center

Reference: Faith H. Brennan, Benjamin T. Noble, Yan Wang et al., “Acute post-injury blockade of α2δ-1 calcium channel subunits prevents pathological autonomic plasticity after spinal cord injury”, Cell Reports, 34(4), 2021. DOI: https://doi.org/10.1016/j.celrep.2020.108667

Provided by Ohio State University Wexner Medical Center

Research Could Change How Blood Pressure Is Managed In Spinal Cord Injury Patients (Medicine)

New research from the International Collaboration on Repair Discoveries (ICORD) challenges the current standard for managing blood pressure in people with spinal cord injury (SCI).


The findings, published today in Nature Communications, could lead to a change in the way newly injured patients have their blood pressure managed, potentially improving their chances of retaining more function in the long term.

This study, led by ICORD principal investigators Dr. Christopher West and Dr. Brian Kwon, demonstrated that following high-thoracic SCI, the heart’s ability to contract is impaired, leading to reduced spinal cord blood flow. High-thoracic SCI generally refers to injuries that affect the abdominal and lower back muscles and the legs, typically resulting in paraplegia, while arm and hand function may not be affected.

Currently, a patient being treated for acute SCI–a traumatic injury that bruises, partially or fully tears the spinal cord–has their blood pressure managed using drugs that cause their blood vessels to constrict in order to increase blood pressure.

In this study, the research team tested an experimental treatment targeting the heart to beat more powerfully, which increased the amount of blood ejected and also increased blood pressure.

“The key difference is that by targeting the heart, we increase blood pressure by increasing blood flow instead of by causing the blood vessels to narrow,” said West. “This is important because by increasing blood flow we can deliver more blood and oxygen to the spinal cord which is expected to minimize the damage at the epicentre of the injury, and therefore reduce injury severity and bleeding in the cord, both of which are expected to improve the chances of people with SCI retaining more function.”

This could mean in the future that an individual who is newly admitted to the hospital may receive a different drug during their initial period of post-injury management. If proven to be effective in humans with SCI, it could improve their chances of retaining more function in the long-term.

“It is important to point out that one of the only things we can currently do for acute SCI patients is to try to optimize the supply of blood and oxygen to the injured spinal cord to prevent further secondary injury,” said Kwon. “We need to seek ways of delivering this care in the most effective manner possible, as any bit of spinal cord function that could be improved upon by novel approaches such as this would potentially be very impactful to a patient.”

References: Williams, A.M., Manouchehri, N., Erskine, E. et al. Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury. Nat Commun 11, 5209 (2020). https://doi.org/10.1038/s41467-020-18905-8

Provided by University of British Columbia

Spinal Cord Stem Cells Can Help Repair After Injury (Neuroscience)

Researchers at Karolinska Institutet have shown how stem cells, together with other cells, repair damaged tissue in the mouse spinal cord. The results are of potential significance to the development of therapies for spinal cord injury.

© gettyimages

There is hope that damage to the spinal cord and brain will one day be treatable using stem cells (i.e. immature cells that can develop into different cell types). Stem cell-like cells have been found in most parts of the adult human nervous system, although it is still unclear how much they contribute to the formation of new, functioning cells in adult individuals.

A joint study by Professor Jonas Frisén’s research group at Karolinska Institutet and their colleagues from France and Japan, and published in Cell Stem Cell, shows how stem cells and several other cell types contribute to the formation of new spinal cord cells in mice and how this changes dramatically after trauma.

The research group has identified a type of stem cell, called an ependymal cell, in the spinal cord. They show that these cells are inactive in the healthy spinal cord, and that the cell formation that takes place does so mainly through the division of more mature cells. When the spinal cord is injured, however, these stem cells are activated to become the dominant source of new cells.

The stem cells then give rise to cells that form scar tissue and to a type of support cell that is an important component of spinal cord functionality. The scientists also show that a certain family of mature cells known as astrocytes produce large numbers of scar-forming cells after injury.

“The stem cells have a certain positive effect following injury, but not enough for spinal cord functionality to be restored,” says Jonas Frisén. “One interesting question now is whether pharmaceutical compounds can be identified to stimulate the cells to form more support cells in order to improve functional recovery after a spinal trauma.”

References: Fanie Barnabé-Heider, Christian Göritz, Hanna Sabelström, Hirohide Takebayashi, Frank W. Pfrieger, Konstantinos Meletis & Jonas Frisén. Origin of new glial cells in the intact and injured adult spinal cord. Cell Stem Cell, 8 October 2010 DOI: 10.1016/j.stem.2010.07.014

Provided by Karolinska Institutet