Promising neuroprotective strategies for traumatic spinal cord injury with a focus on the differential effects among anatomical levels of injury

Traumatic spinal cord injury (SCI) is a devastating condition of motor, sensory, and autonomic dysfunction. The significant cost associated with the management and lifetime care of patients with SCI also presents a major economic burden. For these reasons, there is a need to develop and translate strategies that can improve outcomes following SCI. Given the challenges in achieving regeneration of the injured spinal cord, neuroprotection has been at the forefront of clinical translation. Yet, despite many preclinical advances, there has been limited translation into the clinic apart from methylprednisolone (which remains controversial), hypertensive therapy to maintain spinal cord perfusion, and early decompressive surgery. While there are several factors related to the limited translational success, including the clinical and mechanistic heterogeneity of human SCI, the misalignment between animal models of SCI and clinical reality continues to be an important factor. Whereas most clinical cases are at the cervical level, only a small fraction of preclinical research is conducted in cervical models of SCI. Therefore, this review highlights the most promising neuroprotective and neural reparative therapeutic strategies undergoing clinical assessment, including riluzole, hypothermia, granulocyte colony-stimulating factor, glibenclamide, minocycline, Cethrin (VX-210), and anti-Nogo-A antibody, and emphasizes their efficacy in relation to the anatomical level of injury. Our hope is that more basic research will be conducted in clinically relevant cervical SCI models in order to expedite the transition of important laboratory discoveries into meaningful treatment options for patients with SCI.