Neuroplasticity and regeneration after spinal cord injury.

Spinal cord injury (SCI) is a debilitating condition with significant personal, societal, and economic burden. The highest proportion of traumatic injuries occur at the cervical level, which results in severe sensorimotor and autonomic deficits. Following the initial physical damage associated with traumatic injuries, secondary pro-inflammatory, excitotoxic, and ischemic cascades are initiated further contributing to neuronal and glial cell death. Additionally, emerging evidence has begun to reveal that spinal interneurons undergo subtype specific neuroplastic circuit rearrangements in the weeks to months following SCI, contributing to or hindering functional recovery. The current therapeutic guidelines and standards of care for SCI patients include early surgery, hemodynamic regulation, and rehabilitation. Additionally, preclinical work and ongoing clinical trials have begun exploring neuroregenerative strategies utilizing endogenous neural stem/progenitor cells, stem cell transplantation, combinatorial approaches, and direct cell reprogramming. This review will focus on emerging cellular and noncellular regenerative therapies with an overview of the current available strategies, the role of interneurons in plasticity, and the exciting research avenues enhancing tissue repair following SCI.

Extracellular Matrix and Oxidative Stress Following Traumatic Spinal Cord Injury: Physiological and Pathophysiological Roles and Opportunities for Therapeutic Intervention.

Significance: Traumatic spinal cord injury (SCI) causes significant disruption to neuronal, glial, vascular, and extracellular elements. The spinal cord extracellular matrix (ECM) comprises structural and communication proteins that are involved in reparative and regenerative processes after SCI. In the healthy spinal cord, the ECM helps maintain spinal cord homeostasis. After SCI, the damaged ECM limits plasticity and contributes to inflammation through the expression of damage-associated molecules such as proteoglycans. Recent Advances: Considerable insights have been gained by characterizing the origins of the gliotic and fibrotic scars, which not only reduce the spread of injury but also limit neuroregeneration. These properties likely limit the success of therapies used to treat patients with SCI. The ECM, which is a major contributor to the scars and normal physiological functions of the spinal cord, represents an exciting therapeutic target to enhance recovery post-SCI. Critical Issue: Various ECM-based preclinical therapies have been developed. These include disrupting scar components, inhibiting activity of ECM metalloproteinases, and maintaining iron homeostasis. Biomaterials have also been explored. However, the majority of these treatments have not experienced successful clinical translation. This could be due to the ECM and scars' polarizing roles. Future Directions: This review surveys the complexity involved in spinal ECM modifications, discusses new ECM-based combinatorial strategies, and explores the biomaterials evaluated in clinical trials, which hope to introduce new treatments that enhance recovery after SCI. These topics will incorporate oxidative species, which are both beneficial and harmful in reparative and regenerative processes after SCI, and not often assessed in pertinent literature. Antioxid. Redox Signal. 37, 184-207.