Spinal Cord Injury

Background

Early Stage squareA spinal cord injury (SCI) is an insult to the spinal cord, either by trauma or disease, which results in the disruption of signal transmission between the brain and the rest of the body. SCIs most often arise secondary to a traumatic event, such as a motor vehicle accident. Non-traumatic causes of SCI can be divided into intrinsic cord pathology and extrinsic factors. Intrinsic causes include spinal cord tumors, infection, neurodegenerative disease, and spinal cord vascular disease. Extrinsic causes are more common and include intervertebral disc disease and herniation, epidural hematoma, abscess, and malignancy.

Injuries to the spinal cord are classified as complete or incomplete, with complete injuries resulting in total loss of function below the level of the lesion. Various degrees of motor/sensory function are preserved in incomplete injuries, and symptoms can range from pain at the site of injury to complete paralysis.

The incidence of spinal cord injury in the United States is approximately 12,000 patients per year. As of 2010, it is estimated that about 265,000 Americans are living with SCI. 

Current Treatment

Currently, there is no known method to reverse spinal cord damage. In patients with acute SCI, treatment involves stabilization or traction of the patient to prevent further damage, medication to reduce damage to nerve cells and decrease inflammation and possible surgery to place braces, remove bleeding or fragments. To reduce long-term effects, people with SCI may also benefit from rehabilitation, physical therapy, assistive devices and exercise strategies.  

Additional investigational strategies include spinal cord cooling to help reduce damage, functional electrical stimulation to help restore damaged functions and neural stem cell use to promote neural repair.

Focused Ultrasound Research

Pioneering preclinical research is currently being conducted on the use of FUS to aid in delivering genetic material across the blood-spinal cord barrier (BSCB). A 2015 study entitled “Gene Delivery to the spinal cord using MRI-guided focused ultrasound” by Kullervo Hynynen and collaborators at the University of Toronto and Sunnybrook Research Institute describes the use of FUS in combination with microbubbles to transiently open the BSCB which allowed for non-surgical, targeted gene delivery in a rat model. 

Notable Papers

Song Z, Wang Z, Shen J, Xu S, Hu Z. Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats. Int J Nanomedicine. 2017 Mar 2;12:1717-1729. doi: 10.2147/IJN.S128848. eCollection 2017.

Weber-Adrian D, Thévenot E, O'Reilly MA, Oakden W, Akens MK, Ellens N, Markham-Coultes K, Burgess A, Finkelstein J, Yee AJ, Whyne CM, Foust KD, Kaspar BK, Stanisz GJ, Chopra R, Hynynen K, Aubert I. Gene delivery to the spinal cord using MRI-guided focused ultrasound. Gene Ther. 2015 Jul;22(7):568-77.

Oakden W, Kwiecien JM, O'Reilly MA, Lake EM, Akens MK, Aubert I, Whyne C, Finkelstein J, Hynynen K, Stanisz GJ. A non-surgical model of cervical spinal cord injury induced with focused ultrasound and microbubbles. J Neurosci Methods. 2014 Sep 30;235:92-100. doi: 10.1016/j.jneumeth.2014.06.018.

Y.-S. Tung, F. Vlachos, J. A. Feshitan, M. A. Borden, and E. E. Konofagou, “The mechanism of interaction between focused ultrasound and microbubbles in blood-brain barrier opening in mice.,” J. Acoust. Soc. Am., vol. 130, no. 5, pp. 3059–3067, Nov. 2011.

C. X. Deng, “Targeted drug delivery across the blood-brain barrier using ultrasound technique.,” Ther. Deliv., vol. 1, no. 6, pp. 819–848, Dec. 2010.

     

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