More than a quarter million Americans are living with a spinal cord injury and an estimated 17,000 people will experience a new spinal cord injury every year. At the University of Florida College of Public Health and Health Professions, several faculty members in the departments of physical therapy and speech, language, and hearing sciences are investigating strategies to enhance the health and wellbeing of people with spinal cord injury. These approaches are designed to improve a wide range of functions, including walking and other movements, breathing and airway defense.
These investigators are members of the UF Breathing Research and Therapeutics or BREATHE, Center, and their work includes applications of a novel intervention called acute intermittent hypoxia, which was developed by BREATHE Center director Gordon Mitchell, Ph.D., a professor at the PHHP department of physical therapy.
“We are investigating the concept that modest exposure to intermittent periods of low oxygen, or acute intermittent hypoxia, elicits forms of neuroplasticity in the motor nerve cells that drive diaphragm contractions and breathing,” Mitchell said. “In close collaboration with other BREATHE investigators, we explore how these acute intermittent hypoxia protocols combine with traditional rehabilitation, the impact of combining intermittent hypoxia with a class of drugs known as the ampakines, and the impact of delivery with sub-acute versus chronic spinal cord injury. Our findings inspire the next clinical trials in humans living with chronic spinal cord injury.”
In honor of September’s Spinal Cord Awareness Month, read on to learn more about the work of Emily Fox, David Fuller, Michela Mir, Gordon Mitchell, Sabhya Rana and Alicia Vose.
Emily Fox, Ph.D., D.P.T.
Associate professor, department of physical therapy; Director, Brooks-UF PHHP Research Collaboration; Clinical associate director, UF BREATHE Center
“Our research focuses on increasing understanding of the effects of SCI and advancing rehabilitation approaches to promote recovery after injury. Our lab focuses specifically on strategies to improve walking function, breathing and trunk control since it is a major component in walking, sitting function and breathing! We study noninvasive strategies such as stimulation of the spinal cord and therapeutic intermittent hypoxia to enhance neuroplasticity and the body’s responses to rehabilitation.
My interest in SCI research comes from my work as a clinical physical therapist, working with patients who have experienced a traumatic, life-changing injury. My interest also comes from working with many leaders in SCI rehabilitation and research.
So much inspires me … my biggest inspirations come from the individuals who have been injured, their positivity, perseverance, resilience, gratitude. Every day I see it and am inspired! I’m inspired by the many great leaders who have contributed to clinical care and research and the amazing science that teaches us there is so much more to accomplish, advance and discover to make rehabilitation more effective!”
David Fuller, Ph.D.
Professor, department of physical therapy; PHHP associate dean for research; Associate director, UF BREATHE Center
“Our laboratory focuses on developing new treatments to promote recovery after spinal cord injury. Currently, we are studying how providing increased oxygen shortly after spinal injury can enhance the recovery process. We are also investigating a novel class of drugs, called ampakines, which have shown the ability to improve neural function after spinal injury.
I hope to see treatments develop that can improve the lives of persons living with spinal cord injury. Our group at Florida is particularly interested in therapies involving oxygen. Working with others in the University of Florida BREATHE Center, we are developing novel ways to mitigate neuronal loss and inflammation and also promote neuroplasticity, all by changing inspired oxygen levels.
I’m excited about the potential of our work to improve the lives of persons with spinal cord injury. I also very much appreciate the opportunity to provide meaningful research experiences for undergraduate students, graduate students and postdoctoral fellows.”
Michela Mir, Ph.D., CCC-SLP
Assistant professor, department of speech, language, and hearing sciences; Member, UF BREATHE Center
“Many individuals with SCI have difficulty coughing, which poses a health risk when they need to clear material from their airways and can lead to respiratory infections. Right now, we do not completely understand the range of cough impairments after injury and there are limited options for rehabilitating cough. My research focuses on improving diagnostic and therapeutic methods for cough function and identifying biomarkers that contribute to rehabilitation outcomes. Acute intermittent hypoxia is a promising strategy that improves breathing and limb function in preclinical models and is currently being studied in several human SCI clinical trials.
Working with research participants and the collaborative research opportunities at UF is very exciting and allows us all to learn so much from each other. Using a clinical translational approach not only fosters this collaborative work, but it facilitates more precise application of interventions that leverage neuroplasticity and target mechanisms of dysfunction that could apply to other clinical populations who have similar upper airway impairments, such as cough.
I am motivated to serve the community of individuals who have impaired upper airway function and striving to improve their health and overall well-being. Their experiences inform many processes and research questions, and I have learned so much from them. That path of discovery, learning and service is highly motivating and meaningful.”
Gordon Mitchell, Ph.D.
Professor, department of physical therapy; Director, UF BREATHE Center
“After years of study of neuroplasticity triggered by exposure to acute intermittent hypoxia in rodent models, we came to realize that it was causing plasticity in the nerve cells known as phrenic motor neurons, an important group of motor nerve cells that make the diaphragm contract. We learned this while Christopher Reeve was still alive, and we could not help wonder if this treatment could help individuals like him, who were dependent on a breathing machine (ventilator) to sustain their lives, yet had at least some neural pathways between the brain and spinal cord that could be ‘trained’ to do a better job by triggering neuroplasticity with acute intermittent hypoxia. This hypothesis was first tested in our laboratory by Professor David Fuller, who was then a postdoctoral fellow in my laboratory at the University of Wisconsin; he is now the associate director of the BREATHE Center, associate research dean of PHHP, and a good colleague here at UF!
After many years of study in rodent models, we made the jump to humans and walking instead of breathing in 2010-12. The field has now launched in many directions, a gratifying example of the synergy between fundamental science and clinical translation.
We will continue fundamental discoveries since that is always a ‘pipeline’ for clinical translation. In turn, collaborations through clinical trials inform the need for more studies about how things work so that we can knock down obstacles. Our next focus in studies of animal models concerns the impact of time of day and circadian rhythms on responses to acute intermittent hypoxia. Since there is already evidence that the time of day has a major effect, we have already begun considering pilot trials in humans to determine just how important these differences in therapeutic response may be.”
Sabhya Rana, Ph.D.
Research assistant scientist, department of physical therapy; member, UF BREATHE Center
“Recognizing that respiratory failure is the leading cause of death following SCI, I am driven to develop innovative strategies to preserve and restore independent breathing. My main research objective is to harness spinal cord neuroplasticity to enhance breathing and motor functions after injury. Currently, I am investigating both pharmacological and non-invasive neuromodulation approaches to achieve these goals.
I am enthusiastic about the potential of non-invasive interventions to improve respiratory function following spinal cord injuries. I understand the practical challenges individuals face in accessing effective treatments, which is why I am shaping my research program around therapies that, once validated, can be administered in the comfort of patients’ homes. My goal is to reduce the need for frequent rehabilitation sessions, which are often difficult to access due to insurance limitations.
I believe the future of SCI research is incredibly promising, with several exciting advancements on the horizon. I am particularly enthusiastic about approaches harnessing the synergistic potential of combining neuromodulatory interventions, such as transcutaneous spinal stimulation, with activity-based training. The key idea behind these approaches is that providing targeted spinal circuits with an extra electrical boost, while simultaneously activating them through physical therapy, yields significantly better outcomes than either intervention alone. Additionally, I am excited about the growing focus on precision medicine in SCI research. No two injuries are the same, and individuals vary widely in their response to treatments due to factors like genetics and environmental influences. Tailoring therapies to the specific needs of each patient can lead to more effective interventions.”
Alicia Vose, Ph.D., CCC-SLP
Assistant professor, department of neurology, UF College of Medicine — Jacksonville; Member, UF BREATHE Center; Alumna, PHHP rehabilitation science Ph.D.
“Our lab focuses on investigating the effects of cervical spinal cord injury (SCI) on laryngeal function, particularly its impact on swallowing, coughing and vocal function. Our goal is to characterize these impairments to better understand how changes in laryngeal function affect airway protection and contribute to the risk of aspiration, where excess saliva or liquids enter the upper airway and lungs. Preliminary findings from our lab suggest that even in chronic cervical SCI, subtle deficits in laryngeal function can result in transient aspiration. These deficits often go unnoticed, but can significantly compromise respiratory health by increasing the risk of pneumonia, a serious complication affecting up to two-thirds of individuals with cervical SCI and accounting for 65% of deaths among those with high-level injuries (C1-C4). We believe that poor respiratory health and pneumonia in SCI patients are likely multifactorial. Thus, a central goal of our research is to determine whether changes in laryngeal function and aspiration represent an under-recognized yet profound complication of SCI. To capture these subtle mechanistic changes in laryngeal function, our lab employs advanced diagnostic tools such as high-speed videofluoroscopy and laryngoscopy, which allow us to quantify laryngeal movement and identify aspiration that might otherwise go undetected.
This research has the potential for a profound clinical impact on SCI care by increasing our understanding of modifiable risk factors to optimize care for high-risk individuals. By identifying these factors, we can directly improve the quality of life and health outcomes for people with spinal cord injuries. Second, as a clinical researcher, one of the most exciting aspects is the opportunity to collaborate with basic science colleagues in the BREATHE Center here at UF. This partnership allows us to engage in translational research, exploring the mechanisms of swallowing dysfunction and airway protection in both rodent models and human SCI populations. The use of animal models enables us to conduct comprehensive evaluations of swallowing biomechanics and the underlying mechanisms of dysfunction, which is critical for the future development of mechanistically-based therapeutic interventions to restore swallowing function and reduce aspiration risk. I’m particularly excited about the collaborative environment here at UF, where we bring together a team with unique but complementary expertise in both clinical SCI research and pre-clinical models. The ability to bridge basic and clinical science through translational research is thrilling because it accelerates the path from discovery to practical, patient-centered solutions.”