Intermittent hypoxia and stem cell implants preserve breathing capacity in a rodent model of amyotrophic lateral sclerosis
| Autor: | Nicole L. Nichols, Patrick L. Mulcrone, Irawan Satriotomo, Lisa J. Nashold, Erica A. Dale, Gordon S. Mitchell, Genevieve Gowing, Masatoshi Suzuki, Pablo Avalos, Jacalyn McHugh, Clive N. Svendsen |
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| Rok vydání: | 2012 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Respiratory Therapy Critical Care and Intensive Care Medicine Rats Sprague-Dawley Paralysis medicine Animals Respiratory function Glial Cell Line-Derived Neurotrophic Factor Respiratory system Amyotrophic lateral sclerosis Hypoxia Phrenic nerve Motor Neurons business.industry Superoxide Dismutase Brain-Derived Neurotrophic Factor Amyotrophic Lateral Sclerosis Intermittent hypoxia Articles Motor neuron musculoskeletal system medicine.disease Rats Phrenic Nerve medicine.anatomical_structure nervous system Anesthesia Breathing medicine.symptom Rats Transgenic business Respiratory Insufficiency Inspiratory Capacity Stem Cell Transplantation |
| Zdroj: | American journal of respiratory and critical care medicine. 187(5) |
| ISSN: | 1535-4970 |
| Popis: | 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.To preserve or restore phrenic nerve activity in SOD1(G93A) rats at disease end stage.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.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.AIH-induced respiratory plasticity and stem cell therapy have complementary translational potential to treat breathing deficits in patients with ALS. |
| Databáze: | OpenAIRE |
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