title: Inosine enhances axon sprouting and motor recovery after spinal cord injury.
abstract: Although corticospinal tract axons cannot regenerate long distances after spinal cord injury, they are able to sprout collateral branches rostral to an injury site that can help form compensatory circuits in cases of incomplete lesions. We show here that inosine enhances the formation of compensatory circuits after a dorsal hemisection of the thoracic spinal cord in mature rats and improves coordinated limb use. Inosine is a naturally occurring metabolite of adenosine that crosses the cell membrane and, in neurons, activates Mst3b, a protein kinase that is part of a signal transduction pathway that regulates axon outgrowth. Compared to saline-treated controls, rats with dorsal hemisections that were treated with inosine showed three times as many synaptic contacts between corticospinal tract collaterals and long propriospinal interneurons that project from the cervical cord to the lumbar level. Inosine-treated rats also showed stronger serotonergic reinnervation of the lumbar cord than saline-treated controls, and performed well above controls in both open-field testing and a horizontal ladder rung-walking test. Inosine was equally effective whether delivered intracranially or intravenously, and has been shown to be safe for other indications in humans. Thus, inosine might be a useful therapeutic for improving outcome after spinal cord injury.
authors: Laboratories for Neuroscience Research in Neurosurgery, Children's Hospital, Boston, Massachusetts, United States of America ; F.M. Kirby Neurobiology Center, Children's Hospital, Boston, Massachusetts, United States of America.
authors: Daniel
authors: D
authors: Kim
authors: Laila
authors: L
authors: Zai
authors: Peng
authors: P
authors: Liang
authors: Colleen
authors: C
authors: Schaffling
authors: David
authors: D
authors: Ahlborn
authors: Larry I
authors: LI
authors: Benowitz
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb; D007288:Inosine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D013569:Synapses / Q000187:drug effects / Q000473:pathology
chemical_list: D012701:Serotonin; D007288:Inosine