Daily acute intermittent hypoxia improves breathing function with acute and chronic spinal injury via distinct mechanisms

被引:41
作者
Dougherty, B. J. [1 ]
Terada, J. [1 ,2 ]
Springborn, S. R. [1 ]
Vinit, S. [1 ,3 ]
MacFarlane, P. M. [1 ,4 ]
Mitchell, G. S. [1 ,5 ]
机构
[1] Univ Wisconsin, Dept Comparat Biosci, 2015 Linden Dr W, Madison, WI 53706 USA
[2] Chiba Univ, Grad Sch Med, Dept Respirol, Chiba, Japan
[3] Univ Versailles St Quentin En Yvelines, UFR Sci Sante Simone Veil, INSERM, U1179,End Icap, Montigny Le Bretonneux, France
[4] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA
[5] Univ Florida, Ctr Resp Res & Rehabil, Dept Phys Therapy, McKnight Brain Inst, Gainesville, FL 32610 USA
关键词
Phrenic; Long-term facilitation; Intermittent hypoxia; Plasticity; Spinal cord injury; Serotonin; Adenosine; LONG-TERM FACILITATION; INBRED RAT STRAINS; CORD-INJURY; RECEPTOR ACTIVATION; MOTOR FUNCTION; RECOVERY; HEMISECTION; VENTILATION; SEROTONIN; DIAPHRAGM;
D O I
10.1016/j.resp.2017.05.004
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Daily acute intermittent hypoxia (dAIH) elicits respiratory plasticity, enhancing respiratory motor output and restoring breathing capacity after incomplete cervical spinal injuries (cSCI). We hypothesized that dAIH-induced functional recovery of breathing capacity would occur after both acute (2 weeks) and chronic (8 weeks) cSCI, but through distinct cellular mechanisms. Specifically, we hypothesized that dAIH-induced breathing recovery would occur through serotonin-independent mechanisms 2wks post C2 cervical hemisection (C2Hs), versus serotonin-dependent mechanisms 8wks post C2Hs. In two independent studies, dAIH or sham (normoxia) was initiated 1 week (Study 1) or 7 weeks (Study 2) post-C2Hs to test our hypothesis. Rats were pre-treated with intra-peritoneal vehicle or methysergide, a broad-spectrum serotonin receptor antagonist, to determine the role of serotonin signaling in dAIH-induced functional recovery. Our data support the hypothesis that dAIH-induced recovery of breathing capacity transitions from a serotonin-independent mechanism with acute C2Hs to a serotonin-dependent mechanism with chronic C2Hs. An understanding of shifting mechanisms giving rise to dAIH-induced respiratory motor plasticity is vital for clinical translation of dAIH as a therapeutic modality.
引用
收藏
页码:50 / 57
页数:8
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