Spinal cord injury leads to increases in apnea frequency and duration in spontaneously breathing mice with and without central nervous system 5HT

Abstract

PurposeThe present investigation was designed to explore the impact of serotonin (5HT) on apnea severity and duration, arousal frequency and respiratory stability following spinal cord injury (SCI) in mice.MethodsTelemetry transmitters were surgically implanted in wild type mice (Tph2+/+) (n = 4) and tryptophan hydroxylase 2 knockout mice (Tph2−/−) (n = 3) to measure electroencephalography, core body temperature and gross motor activity. Following recovery, the Tph2+/+ and Tph2−/− mice were placed in whole body plethysmographs and measures of apnea severity, coefficient of variation of the duration of each breath, duration index and arousal frequency during non‐rapid eye movement sleep were determined for 6 hours. Following these measures, a C2 hemisection of the spinal cord was completed and the physiological measurements were repeated 4 and 21 days following hemisection.ResultsFollowing SCI the number of apnea events increased in the Tph2+/+ (baseline vs. 21 days: 52.1 ± 17.4 vs. 106.4 ± 21.2 events/hr, p = 0.02) and the Tph2−/− mice (30.7 ± 9.6 vs. 77.5 ± 34.1, p = 0.02). The coefficient of variance of the duration of each breath also increased after SCI (Tph2+/+ 0.25 ± 0.02 vs. 0.30 ± 0.06, Tph2−/− 0.25 ± 0.02 vs. 0.35 ± 0.06, p = 0.07). Likewise, the apnea duration index increased following SCI in the Tph2+/+ (baseline vs. 21 days: 2.4 ± 0.05 vs. 3.2 ± 0.6 events/hr, p = 0.047) and Tph2−/− mice (baseline vs. 21 days: 2.6 ± 0.5 vs. 3.8 ± 0.5 events/hr, p = 0.047). Lastly, the number of arousals increased after SCI in both groups (Tph2+/+ 19.0 ± 4.6 vs. 39.1 ± 13.8, Tph2−/− 5.1 ± 0.9 vs. 35.6 ± 19.4 arousal/hr, p = 0.03).ConclusionsSCI leads to an increase in the frequency and duration of apneic events, which is coupled to an increase in the number of arousals. Likewise, alterations in the coefficient of variation indicate that breathing is more variable when present. However, the role of 5HT in mediating arousals and stabilizing breathing is less certain in this small sample size, since modifications in breathing stability and arousal frequency was not statistically different in the Tph2+/+ and Tph2−/− mice following SCI.Support or Funding InformationDepartment of Veterans Affairs (I01BX003946 & 15SRCS003 JHM)