title: Arylsulfatase B improves locomotor function after mouse spinal cord injury.
abstract: Bacterial chondroitinase ABC (ChaseABC) has been used to remove the inhibitory chondroitin sulfate chains from chondroitin sulfate proteoglycans to improve regeneration after rodent spinal cord injury. We hypothesized that the mammalian enzyme arylsulfatase B (ARSB) would also enhance recovery after mouse spinal cord injury. Application of the mammalian enzyme would be an attractive alternative to ChaseABC because of its more robust chemical stability and reduced immunogenicity. A one-time injection of human ARSB into injured mouse spinal cord eliminated immunoreactivity for chondroitin sulfates within five days, and up to 9 weeks after injury. After a moderate spinal cord injury, we observed improvements of locomotor recovery assessed by the Basso Mouse Scale (BMS) in ARSB treated mice, compared to the buffer-treated control group, at 6 weeks after injection. After a severe spinal cord injury, mice injected with equivalent units of ARSB or ChaseABC improved similarly and both groups achieved significantly more locomotor recovery than the buffer-treated control mice. Serotonin and tyrosine hydroxylase immunoreactive axons were more extensively present in mouse spinal cords treated with ARSB and ChaseABC, and the immunoreactive axons penetrated further beyond the injury site in ARSB or ChaseABC treated mice than in control mice. These results indicate that mammalian ARSB improves functional recovery after CNS injury. The structural/molecular mechanisms underlying the observed functional improvement remain to be elucidated.
authors.affiliation: W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Myungsik
authors.initials: M
authors.lastname: Yoo
authors.forename: Muntasir
authors.initials: M
authors.lastname: Khaled
authors.forename: Kurt M
authors.initials: KM
authors.lastname: Gibbs
authors.forename: Jonghun
authors.initials: J
authors.lastname: Kim
authors.forename: Björn
authors.initials: B
authors.lastname: Kowalewski
authors.forename: Thomas
authors.initials: T
authors.lastname: Dierks
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D019765:Chondroitin ABC Lyase / Q000494:pharmacology; D002809:Chondroitin Sulfates / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008124:Locomotion / Q000187:drug effects*; D051379:Mice; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D002809:Chondroitin Sulfates; D020051:N-Acetylgalactosamine-4-Sulfatase; C581941:ARSB protein, human; D019765:Chondroitin ABC Lyase