CM101-mediated recovery of walking ability in adult mice paralyzed by spinal cord injury.
CM101, an antiangiogenic polysaccharide derived from group B streptococcus, was administered by i.v. injection 1 hr post-spinal-cord crush injury in an effort to prevent inflammatory angiogenesis and gliosis (scarring) in a mouse model. We postulated that gliosis would sterically prevent the reestablishment of neuronal connectivity; thus, treatment with CM101 was repeated every other day for five more infusions for the purpose of facilitating regeneration of neuronal function. Twenty-five of 26 mice treated with CM101 survived 28 days after surgery, and 24 of 26 recovered walking ability within 2-12 days. Only 6 of 14 mice in the control groups survived 24 hr after spinal cord injury, and none recovered function in paralyzed limbs. MRI analysis of injured untreated and treated animals showed that CM101 reduced the area of damage at the site of spinal cord compression, which was corroborated by histological analysis of spinal cord sections from treated and control animals. Electrophysiologic measurements on isolated central nervous system and neurons in culture showed that CM101 protected axons from Wallerian degeneration; reversed gamma-aminobutyrate-mediated depolarization occurring in traumatized neurons; and improved recovery of neuronal conductivity of isolated central nervous system in culture.
Wamil
A W
AW
Department of Surgery, Vanderbilt University, Nashville, TN 37232, USA.
Wamil
B D
BD
Hellerqvist
C G
CG
D000818:Animals; D001427:Bacterial Toxins / Q000627:therapeutic use*; D005911:Gliosis / Q000517:prevention & control; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008279:Magnetic Resonance Imaging; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D009409:Nerve Crush; D010243:Paralysis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D011135:Polysaccharides, Bacterial / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D013292:Streptococcus agalactiae; D013997:Time Factors
D001427:Bacterial Toxins; D011135:Polysaccharides, Bacterial; C032263:streptococcal polysaccharide type III group B