Enhanced recovery of breathing capacity from combined adenosine 2A receptor inhibition and daily acute intermittent hypoxia after chronic cervical spinal injury.

Autor: Navarrete-Opazo A; Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA; Teletón Children Rehabilitation Institute, Alameda 4620, Santiago, Chile., Dougherty BJ; Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA., Mitchell GS; Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA; Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA. Electronic address: gsmitche@phhp.ufl.edu.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2017 Jan; Vol. 287 (Pt 2), pp. 93-101. Date of Electronic Publication: 2016 Apr 11.
DOI: 10.1016/j.expneurol.2016.03.026
Abstrakt: Daily acute intermittent hypoxia (dAIH) improves breathing capacity after C2 spinal hemisection (C2HS) in rats. Since C2HS disrupts spinal serotonergic innervation below the injury, adenosine-dependent mechanisms underlie dAIH-induced functional recovery 2weeks post-injury. We hypothesized that dAIH-induced functional recovery converts from an adenosine-dependent to a serotonin-dependent, adenosine-constrained mechanism with chronic injury. Eight weeks post-C2HS, rats began dAIH (10, 5-min episodes, 10.5% O 2 ; 5-min intervals; 7days) followed by AIH 3× per week (3×wAIH) for 8 additional weeks with/without systemic A 2A receptor inhibition (KW6002) on each AIH exposure day. Tidal volume (V T ) and bilateral diaphragm (Dia) and T2 external intercostal motor activity were assessed in unanesthetized rats breathing air and during maximum chemoreflex stimulation (MCS: 7% CO 2 , 10.5% O 2 ). Nine weeks post-C2HS, dAIH increased V T versus time controls (p<0.05), an effect enhanced by KW6002 (p<0.05). dAIH increased bilateral Dia activity (p<0.05), and KW6002 enhanced this effect in contralateral (p<0.05) and ipsilateral Dia activity (p<0.001), but not T 2 inspiratory activity. Functional benefits of combined AIH plus systemic A 2A receptor inhibition were maintained for 4weeks. Thus, in rats with chronic injuries: 1) dAIH improves V T and bilateral diaphragm activity; 2) V T recovery is enhanced by A 2A receptor inhibition; and 3) functional recovery with A2A receptor inhibition and AIH "reminders" last 4weeks. Combined dAIH and A 2A receptor inhibition may be a simple, safe, and effective strategy to accelerate/enhance functional recovery of breathing capacity in patients with respiratory impairment from chronic spinal injury.
Competing Interests: Authors declare no conflict of interest, financial or otherwise.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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