Premium
Cervical spinal demyelination with ethidium bromide reversibly impairs phrenic nerve activity in adult rats
Author(s) -
Johnson Rebecca A.,
Nichols Nicole L.,
Duncan Ian D.,
Punzo Antonio M.,
Mitchell Gordon S.
Publication year - 2012
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.26.1_supplement.704.7
Subject(s) - medicine , hypercapnia , remyelination , intermittent hypoxia , phrenic nerve , hypoxia (environmental) , hypoxic ventilatory response , anesthesia , ventilation (architecture) , respiratory system , myelin , central nervous system , chemistry , mechanical engineering , organic chemistry , oxygen , obstructive sleep apnea , engineering
Respiratory complications are a major cause of morbidity/mortality in many diseases associated with demyelination. Little is known concerning mechanisms whereby lack of myelin impairs ventilation, or how patients compensate for such changes (compensatory plasticity). We tested the hypothesis that respiratory function is diminished with focal spinal demyelination using unilateral ethidium bromide (EB) injections into C2 bulbospinal tracts. Ventilation (plethysmography) and phrenic nerve activity (neurophysiological recordings) were made 7–21 days post‐EB at baseline and in hypoxia±hypercapnia. EB produced maximal demyelination at day 7 with spontaneous remyelination in 14–21 days (all P <0.05). Ventilation did not differ between groups (all P >0.05). Ipsilateral phrenic nerve voltage was lower than the contralateral voltage 7 days post‐EB during hypoxia and hypoxia/hypercapnia (both P <0.05), as well as the ipsi‐ and contralateral voltage of SHAM and 14 day rats in all conditions (all P <0.05). Average voltage ratios (ipsi:contra) correlated to lesion size at baseline ( P <0.05) and were signficantly reduced in 7 day rats (all P <0.05). Our reversible demyelination model provides a powerful tool to study respiratory motor impairment, mechanisms underlying compensatory plasticity/spontaneous recovery, and therapies to reduce demyelination and its associated respiratory motor dysfunction. Support: Supported by grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources (NCRR), National Institutes of Health (NIH).