Withanoside IV improves hindlimb function by facilitating axonal growth and increase in peripheral nervous system myelin level after spinal cord injury.
Although methylprednisolone is the clinically standard medication and almost the only therapy for spinal cord injury (SCI), its effect on functional recovery remains questionable. Transplantation strategies using sources such as neural stem cells and embryonic spinal cord still have some hurdles to overcome before practical applications become available. We therefore aimed to develop a practical medication for SCI. Per oral treatment with withanoside IV, which was previously shown to regenerate neuronal networks in the brain, improved locomotor functions in mice with SCI. In the spinal cord after SCI, axons were crushed in the white matter and gray matter, and central nervous system (CNS) myelin level decreased. In mice treated with withanoside IV (10micromol/kg body weight/day, for 21 days), axonal density and peripheral nervous system (PNS) myelin level increased. The loss of CNS myelin and increase in reactive gliosis were not affected by withanoside IV. These results suggest that oral administration of withanoside IV may ameliorate locomotor functions by facilitating both axonal regrowth and increase in PNS myelin level.
Nakayama
Natsuki
N
Division of Biofunctional Evaluation, Research Center for Ethnomedicine, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
Tohda
Chihiro
C
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000187:drug effects*; D004195:Disease Models, Animal; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects; D035002:Lower Extremity / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009185:Myelin Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects; D016900:Neurofilament Proteins / Q000378:metabolism; D017933:Peripheral Nervous System / Q000473:pathology*; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013997:Time Factors
D009185:Myelin Proteins; D016900:Neurofilament Proteins; C516508:ashwagandhanolide; C051774:neurofilament protein H; C523922:withanoside IV; D004875:Ergosterol