Past, Present, and Future: The Journey of Spinal Cord Injury and Concussion Research

By Eileen (Xiao Yu) Liu

Our current understanding on the different types of trauma that can affect an individual’s nervous system, such as spinal cord injury and concussion, has not been without difficulty. Spinal cord injury is damage to the spinal cord, impacting the conduction of sensory and motor signals between the brain and the body. Concussion is a type of mild traumatic brain injury; as defined by the International Consensus Conference on Concussion in Sports, it is a “complex pathophysiological process affecting the brain, induced by traumatic biomechanical force”.1 Although we have made terrific progress in our understanding of spinal cord injury and concussion, and how best to prevent these conditions, Dr. Charles H. Tator, who has immersed himself in these two fields for the past 30 years, believes there are still important fundamentals questions that remain to be answered.

Dr. Tator is a pioneer in the research of concussion and spinal cord injury. He is currently a Scientist at the Krembil Brain Institute and the Director of the Canadian Concussion Centre at Toronto Western Hospital. Dr. Tator obtained his medical degree from the University of Toronto in 1961. During his residency, Dr. Tator became involved in the care of patients with spinal cord injury. He also observed that this patient population suffered from poor quality of life and high mortality rates due to the limited treatment options available at that time. Thus, Dr. Tator felt there was a clinical urgency for more research in spinal cord injury.

Dr. Tator’s resulting experimental research has sought to improve the prognosis and outcome for patients with spinal cord injury. Earlier in his career, Dr. Tator contributed to the grading and scoring of spinal cord injury.2 He and his team also devised injury models including small animal models of acute spinal cord injury induced by inflatable cuffs or compression clips to deliver injury.3-5 Furthermore, he demonstrated that earlier management following injury is highly beneficial for recovery and outcome.6,7 Recently, Dr. Tator and his team researched the use of antibodies against inhibitor proteins, which accumulate at the site of injury and impede the recovery process. This treatment promotes functional recovery after spinal cord injury in experimental models.8,9 His group also studied the natural defense mechanism that the endogenous spinal cord stem cells can offer following injury, along with ways to enhance this underlying process of recovery and regeneration. Altogether, his work has been instrumental in furthering our understanding of spinal cord injury and has gained him immense recognition.

As time passed, Dr. Tator noticed an accumulation of young individuals who suffered from head injuries as a result of sports activities, motor vehicle collisions, and other recreational activities. This observation led to his involvement in concussion research. Concussion is defined as a transient disturbance of brain function due to trauma. However, the exact location of injury cannot be easily deciphered. Dr.

Tator described the location of concussion symptoms to be everywhere in the brain. Information provided by various highresolution imaging modalities suggests that more attention should be directed to the brainstem, which has always been thought as a major source of concussion symptoms. However, the animal models for concussion have not been sufficient to validate this theory. Currently, rodents are more frequently used for modeling and studying brain injury. The relevance of these brain injury models to human concussion is debatable because the amount of linear and angular acceleration during a concussion event experienced

Dr. Charles H. Tator MD, PhD, FRSCS, FACS Professor, Department of Surgery & Institute of Medical Science, University

by the human brain is very different than that of a mouse or a rat. In addition to animal models and brain imaging, biofluid biomarkers are also important for understanding concussion. Biomarkers of concussion have been studied in the biological fluids of patients, including the plasma, serum, saliva and cerebrospinal fluid. From years of research, we now have a whole range of biofluid biomarkers for potential indicators of injury to the brain or spinal cord. If used in combination, these biomarkers may someday identify the signature of concussion. Clinical application of these biomarkers requires additional work to improve their sensitivity and specificity. With the absence of diagnostic biomarkers, the current diagnosis of concussion relies on the signs and symptoms following injury. These are often self-reported signs and symptoms by the patient in addition to the results from various clinical assessment tools. Other methods being applied to diagnosing concussion by Dr. Tator’s team is artificial intelligence, neuropsychological evaluation, biomarkers of the blood and cerebrospinal fluid, eye movement tracking, and various brain imaging modalities including magnetic resonance imaging to augment the diagnosis of concussion.

Following a concussion, approximately 25% of patients experience persistent concussion symptoms after 30 days. For some, these symptoms can last from months to years, and may even persist for their lifetime. Currently, Dr. Tator is conducting research on enhancing early return to work or school following a concussion. A frequent symptom that concussed individuals develop is computer screen intolerance. This is a major concern because of how heavily we rely on the use of computers on a daily basis. Dr. Tator and his team aim to find a solution by testing alternative screens that can be used by these patients.

As a clinician-scientist, Dr. Tator endorses the concept that scientists can pursue multiple scientific interests, and these can be in the same or different fields. For Dr. Tator, an immense sense of balance in his neurotrauma research came from having one major scientific interest in laboratory research in spinal cord injury, and another in clinical research in concussion. Although there is still a long road ahead in both areas, Dr. Tator is hopeful there will be significant improvements in treatment of patients with concussion and spinal cord injury in the next five to ten years.

References

1. McCrory P, Meeuwisse WH, Aubry M, et al. Consensus statement on concussion in sport: the 4th International Conference on Concussion in Sport held in Zurich, November 2012. Br J Sports Med 47, 250-258, doi:10.1136/bjsports-2013-092313 (2013).

2. Tator CH, Rowed DW & Schwartz ML. Sunnybrook cord injury scales for assessing neurological injury and neurological recovery. (Raven Press New York, 1982).

3. Tator CH. Acute spinal cord injury in primates produced by an inflatable extradural cuff. Can J Surg 16, 222-231 (1973).

4. Tator CH. Experimental circumferential compression injury of primate spinal cord. Proc Veterans Adm Spinal Cord Inj Conf 18, 2-5 (1971).

5. Rivlin AS & Tator CH. Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg Neurol 10, 38-43 (1978).

6. Tator CH & Rowed DW. Current concepts in the immediate management of acute spinal cord injuries. Canadian Medical Association journal 121, 1453-1464 (1979).

7. Tator CH & Edmonds VE. Acute spinal cord injury: analysis of epidemiologic factors. Can J Surg 22, 575-578 (1979).

8. Mothe AJ, Jacobson PB, Caprelli M, et al. Delayed administration of elezanumab, a human anti-RGMa neutralizing monoclonal antibody, promotes recovery following cervical spinal cord injury. Neurobiol Dis 172, 105812, doi:10.1016/j.nbd.2022.105812 (2022).

9. Mothe AJ, Coelho M, Huang L, et al. Delayed administration of the human anti-RGMa monoclonal antibody elezanumab promotes functional recovery including spontaneous voiding after spinal cord injury in rats. Neurobiol Dis 143, 104995, doi:10.1016/j. nbd.2020.104995 (2020).