title: Intermittent hypoxia and stem cell implants preserve breathing capacity in a rodent model of amyotrophic lateral sclerosis.
abstract: BACKGROUND
  Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing paralysis and death from respiratory failure. Strategies to preserve and/or restore respiratory function are critical for successful treatment. Although breathing capacity is maintained until late in disease progression in rodent models of familial ALS (SOD1(G93A) rats and mice), reduced numbers of phrenic motor neurons and decreased phrenic nerve activity are observed. Decreased phrenic motor output suggests imminent respiratory failure.
  
  
  OBJECTIVE
  To preserve or restore phrenic nerve activity in SOD1(G93A) rats at disease end stage.
  
  
  METHODS
  SOD1(G93A) rats were injected with human neural progenitor cells (hNPCs) bracketing the phrenic motor nucleus before disease onset, or exposed to acute intermittent hypoxia (AIH) at disease end stage.
  
  
  RESULTS
  The capacity to generate phrenic motor output in anesthetized rats at disease end stage was: (1) transiently restored by a single presentation of AIH; and (2) preserved ipsilateral to hNPC transplants made before disease onset. hNPC transplants improved ipsilateral phrenic motor neuron survival.
  
  
  CONCLUSIONS
  AIH-induced respiratory plasticity and stem cell therapy have complementary translational potential to treat breathing deficits in patients with ALS.
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Nichols
authors.forename: Genevieve
authors.initials: G
authors.lastname: Gowing
authors.forename: Irawan
authors.initials: I
authors.lastname: Satriotomo
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Nashold
authors.forename: Erica A
authors.initials: EA
authors.lastname: Dale
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Pablo
authors.initials: P
authors.lastname: Avalos
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Mulcrone
authors.forename: Jacalyn
authors.initials: J
authors.lastname: McHugh
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Mitchell
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000628:therapy*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D000860:Hypoxia; D007320:Inspiratory Capacity; D008297:Male; D009046:Motor Neurons / Q000378:metabolism; D010791:Phrenic Nerve / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012131:Respiratory Insufficiency / Q000517:prevention & control*; D012138:Respiratory Therapy / Q000379:methods*; D033581:Stem Cell Transplantation; D013482:Superoxide Dismutase
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase