title: A conditioning lesion provides selective protection in a rat model of Amyotrophic Lateral Sclerosis.
abstract: BACKGROUND
  Amyotrophic Lateral Sclerosis (ALS) is neurodegenerative disease characterized by muscle weakness and atrophy due to progressive motoneuron loss. The death of motoneuron is preceded by the failure of neuromuscular junctions (NMJs) and axonal retraction. Thus, to develop an effective ALS therapy you must simultaneously preserve motoneuron somas, motor axons and NMJs. A conditioning lesion has the potential to accomplish this since it has been shown to enhance neuronal survival and recovery from trauma in a variety of contexts.
  
  
  RESULTS
  To test the effects of a conditioning lesion in a model of familial ALS we administered a tibial nerve crush injury to presymptomatic fALS(G93A) rats. We examined its effects on motor function, motoneuron somas, motor axons, and NMJs. Our experiments revealed a novel paradigm for the conditioning lesion effect. Specifically we found that the motor functional decline in fALS(G93A) rats that received a conditioning lesion was delayed and less severe. These improvements in motor function corresponded to greater motoneuron survival, reduced motor axonopathy, and enhanced NMJ maintenance at disease end-stage. Furthermore, the increased NMJ maintenance was selective for muscle compartments innervated by the most resilient (slow) motoneuron subtypes, but was absent in muscle compartments innervated by the most vulnerable (fast fatigable) motoneuron subtypes.
  
  
  CONCLUSIONS
  These findings support the development of strategies aimed at mimicking the conditioning lesion effect to treat ALS as well as underlined the importance of considering the heterogeneity of motoneuron sub-types when evaluating prospective ALS therapeutics.
authors.affiliation: Department of Neurosurgery, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Colin K
authors.initials: CK
authors.lastname: Franz
authors.forename: Eric T
authors.initials: ET
authors.lastname: Quach
authors.forename: Christina A
authors.initials: CA
authors.lastname: Krudy
authors.forename: Thais
authors.initials: T
authors.lastname: Federici
authors.forename: Michele A
authors.initials: MA
authors.lastname: Kliem
authors.forename: Brooke R
authors.initials: BR
authors.lastname: Snyder
authors.forename: Bethwel
authors.initials: B
authors.lastname: Raore
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Boulis
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism; D002470:Cell Survival; D015925:Cryopreservation; D004195:Disease Models, Animal; D009046:Motor Neurons / Q000473:pathology; D053580:Muscle Strength; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051381:Rats; D055647:Rats, Transgenic; D013119:Spinal Cord Injuries / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D020196:Trauma, Nervous System / Q000473:pathology / Q000601:surgery*
chemical_list: D013482:Superoxide Dismutase