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Spinally delivered ampakine CX717 increases phrenic motor output in adult rats.

Authors :
Thakre PP
Sunshine MD
Fuller DD
Source :
Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2022 Feb; Vol. 296, pp. 103814. Date of Electronic Publication: 2021 Nov 11.
Publication Year :
2022

Abstract

Ampakines are synthetic molecules that allosterically modulate AMPA-type glutamate receptors. We tested the hypothesis that delivery of ampakines to the intrathecal space could stimulate neural drive to the diaphragm. Ampakine CX717 (20 mM, dissolved in 10 % HPCD) or an HPCD vehicle solution were delivered via a catheter placed in the intrathecal space at the fourth cervical segment in urethane-anesthetized, mechanically ventilated adult male Sprague-Dawley rats. The electrical activity of the phrenic nerve was recorded for 60-minutes following drug application. Intrathecal application of CX717 produced a gradual and sustained increase in phrenic inspiratory burst amplitude (n = 10). In contrast, application of HPCD (n = 10) caused no sustained change in phrenic motor output. Phrenic burst rate, heart rate, and mean arterial pressure were similar between CX717 and HPCD treated rats. We conclude that intrathecally delivered ampakines can modulate phrenic motor output. This approach may have value for targeted induction of spinal neuroplasticity in the context of neurorehabiliation.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1878-1519
Volume :
296
Database :
MEDLINE
Journal :
Respiratory physiology & neurobiology
Publication Type :
Academic Journal
Accession number :
34775071
Full Text :
https://doi.org/10.1016/j.resp.2021.103814