Revisiting the immune landscape post spinal cord injury: More than black and white

Spinal cord injury (SCI) induced catastrophic neurological disability is currently incurable, especially in elderly patients. Due to the limited axon regeneration capacity and hostile microenvironment in the lesion site, essential neural network reconstruction remains challenging. Owing to the blood-spinal cord barrier (BSCB) created immune cells and cytokines isolation, the immune elements were incorrectly recognized as innocent bystanders during the SCI pathological process traditionally. Emerging evidence demonstrated that the central nervous system (CNS) is an "immunological quiescent" rather than "immune privileged" area, and the CNS-associated immune response played mixed roles which dedicate beneficial and detrimental contributions throughout the SCI process. Consequently, coordinating double-edged immunomodulation is vital to promote tissue repair and neurological recovery post-SCI. The comprehensive exploration and understanding of the immune landscape post-SCI are essential in establishing new avenues for further basic and clinical studies. In this context, this review summarizes the recent significant breakthroughs in key aspects of SCI-related immunomodulation, including innate and adaptive immune response, immune organ changes, and holistic immune status modification. Moreover, the currently existing immune-oriented therapies for SCI will be outlined.