Chemogenetic activation of the diaphragm after spinal cord injury in rats

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology Pub Date : 2025-03-26 DOI:10.1016/j.resp.2025.104421

Ethan S. Benevides , Sabhya Rana , David D. Fuller

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引用次数: 0

Abstract

We tested the hypothesis that activation of DREADDs in the mid-cervical spinal cord could restore diaphragm activation during spontaneous breathing after cervical spinal cord injury (SCI). Adult Sprague Dawley rats (n = 7) received bilateral mid-cervical ventral horn injections of an AAV construct encoding an excitatory DREADD (AAV9-hSyn-HA-hM3D(Gq)-mCherry; titer: 2.44 × 10¹³ vg/mL). Subsequently, diaphragm electromyogram (EMG) activity was recorded during spontaneous breathing under isoflurane anesthesia. The selective DREADD ligand JHU37160 (J60) was administered intravenously at acute (3 days), sub-acute (2 weeks), and chronic (2 months) timepoints following cervical hemilesion at spinal level C2. J60 administration resulted in robust increases in diaphragm EMG output at all timepoints, and near-complete restoration of diaphragm EMG activity from the paralyzed hemi-diaphragm in 50 % of trials. Administration of J60 to DREADD naïve, spinal intact rats (n = 8) did not produce an increase in diaphragm activity. These proof-of-concept results indicate that refinement of this technique may provide a strategy for improving diaphragm activation after cervical SCI.

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来源期刊

Respiratory Physiology & Neurobiology 医学-呼吸系统

CiteScore

4.80

自引率

8.70%

发文量

104

审稿时长

54 days

期刊介绍： Respiratory Physiology & Neurobiology (RESPNB) publishes original articles and invited reviews concerning physiology and pathophysiology of respiration in its broadest sense. Although a special focus is on topics in neurobiology, high quality papers in respiratory molecular and cellular biology are also welcome, as are high-quality papers in traditional areas, such as: -Mechanics of breathing- Gas exchange and acid-base balance- Respiration at rest and exercise- Respiration in unusual conditions, like high or low pressure or changes of temperature, low ambient oxygen- Embryonic and adult respiration- Comparative respiratory physiology. Papers on clinical aspects, original methods, as well as theoretical papers are also considered as long as they foster the understanding of respiratory physiology and pathophysiology.