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Repetitive Hypercapnia and Hypercapnic Hypoxia Slows Disease Progression in a Rodent Model of Amyotrophic Lateral Sclerosis (ALS)
Author(s) -
Nashold Lisa J,
Schumacher Bryan T,
Mitchell Gordon S
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.784.7
Subject(s) - hypercapnia , amyotrophic lateral sclerosis , hypoxia (environmental) , sod1 , medicine , endocrinology , anesthesia , respiratory system , chemistry , disease , oxygen , organic chemistry
Rats over‐expressing a mutated form of superoxide dismutase (SOD1 G93A ) exhibit progressive motor neuron degeneration and paralysis, and are a common model of familial ALS. We previously made the chance observation that weekly exposure to graded hypercapnia (5% and 7% CO 2 ; 20 min) followed by hypercapnic hypoxia (7% CO 2 in 10% O 2 20 min) apparently delayed disease progression. In this uncontrolled comparison, treated rats were 16 days older at a defined end stage (>20% decrease in body mass) vs untreated littermates (p<0.05). Here we studied this protocol under controlled conditions. Eleven mutant SOD1 G93A rats were paired with a mutant littermate of the same sex; within each pair, 1 rat was treated 3 times per week with the hypercapnia/hypoxia protocol and the other was exposed to air (sham). Exposures were performed from 82 days of age until one rat within the pair reached end‐stage. Rats were perfused to enable counts of surviving motor neurons (analysis underway). Decreases in body mass slowed in treated rats on the day of sacrifice (untreated: 19% +/‐2%, treated: 10% +/‐2%; p <0.05). In 7 of 11 pairs, untreated rats reached end‐stage first (p=0.06); treated rats tended to be older (164+/‐3; n = 4) vs untreated rats at end‐stage (149+/‐6; n = 7; p=0.11). Repetitive hypercapnia may slow disease progression and increase survival in SOD1 G93A rats. Further studies to test this hypothesis are underway. NIH NS057778 and RR023916