xanthofulvin and Spinal-Cord-Injuries

Topics: Animals; Axons; Cell Transplantation; Chondroitin ABC Lyase; Chondroitin Sulfate Proteoglycans; Chromones; Embryonic Stem Cells; Humans; Nerve Growth Factors; Nerve Regeneration; Olfactory Bulb; Schwann Cells; Semaphorin-3A; Spinal Cord Injuries; Transplantation, Autologous; Xanthones

Axons in the adult mammalian central nervous system (CNS) exhibit little regeneration after injury. It has been suggested that several axonal growth inhibitors prevent CNS axonal regeneration. Recent research has demonstrated that semaphorin3A (Sema3A) is one of the major inhibitors of axonal regeneration. We identified a strong and selective inhibitor of Sema3A, SM-216289, from the fermentation broth of a fungal strain. To examine the effect of SM-216289 in vivo, we transected the spinal cord of adult rats and administered SM-216289 into the lesion site for 4 weeks. Rats treated with SM-216289 showed substantially enhanced regeneration and/or preservation of injured axons, robust Schwann cell-mediated myelination and axonal regeneration in the lesion site, appreciable decreases in apoptotic cell number and marked enhancement of angiogenesis, resulting in considerably better functional recovery. Thus, Sema3A is essential for the inhibition of axonal regeneration and other regenerative responses after spinal cord injury (SCI). These results support the possibility of using Sema3A inhibitors in the treatment of human SCI.

Topics: alpha-Defensins; Animals; Cell Movement; Cells, Cultured; Chick Embryo; Chlorocebus aethiops; Chromones; COS Cells; Drug Evaluation, Preclinical; Female; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Neurons; Nerve Regeneration; Rats; Rats, Sprague-Dawley; Rats, Wistar; Schwann Cells; Semaphorin-3A; Spinal Cord; Spinal Cord Injuries; Xanthones