Abstract: Regenerative capacity of the central nervous system (CNS) is unevenly distributed among vertebrates. While most mammalian species including humans elicit limited repair following CNS injury or disease, highly regenerative vertebrates including urodele amphibians and teleost fish spontaneously reverse CNS damage. Teletost zebrafish (danio rerio) are tropical freshwater fish that proved to be an excellent vertebrate model of successful CNS regeneration. Differential neuronal, glial, and immune injury responses underlie disparate injury outcomes between highly regenerative zebrafish and poorly regenerative mammals. This article describes complications associated with neuronal repair following spinal cord injury (SCI) in poorly regenerative mammals and highlights intersecting modes of plasticity and regeneration in highly regenerative zebrafish (Figures 1 and 2). Comparative approaches evaluating immunoglial SCI responses were recently reviewed elsewhere (Reyes and Mokalled, 2024)