Diminished gastric prokinetic response to ghrelin in a rat model of spinal cord injury

E. M. Besecker, A. R. White, Gregory Holmes

Research output: Contribution to journalArticle

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Abstract

Background: Patients with cervical or high-thoracic spinal cord injury (SCI) often present reduced gastric emptying and early satiety. Ghrelin provokes motility via gastric vagal neurocircuitry and ghrelin receptor agonists offer a therapeutic option for gastroparesis. We have previously shown that experimental high-thoracic injury (T3-SCI) diminishes sensitivity to another gastrointestinal peptide, cholecystokinin. This study tests the hypothesis that T3-SCI impairs the vagally mediated response to ghrelin. Methods: We investigated ghrelin sensitivity in control and T3-SCI rats at 3-days or 3-weeks after injury utilizing: (i) acute (3-day post-injury) fasting and post-prandial serum levels of ghrelin; (ii) in vivo gastric reflex recording following intravenous or central brainstem ghrelin; and (iii) in vitro whole cell recording of neurons within the dorsal motor nucleus of the vagus (DMV). Key Results: The 2-day food intake of T3-SCI rats was reduced while fasting serum ghrelin levels were higher than in controls. Intravenous and fourth ventricle ghrelin increased in vivo gastric motility in fasted 3-day control rats but not fasted T3-SCI rats. In vitro recording of DMV neurons from 3-day T3-SCI rats were insensitive to exogenous ghrelin. For each measure, vagal responses returned after 3-weeks. Conclusions and Inferences: Hypophagia accompanying T3-SCI produces a significant and physiologically appropriate elevation in serum ghrelin levels. However, higher ghrelin levels did not translate into increased gastric motility in the acute stage of T3-SCI. We propose that this may reflect diminished sensitivity of peripheral vagal afferents to ghrelin or a reduction in the responsiveness of medullary gastric vagal neurocircuitry following T3-SCI.

Original languageEnglish (US)
Article numbere13258
JournalNeurogastroenterology and Motility
Volume30
Issue number4
DOIs
StatePublished - Apr 1 2018

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Ghrelin
Spinal Cord Injuries
Stomach
Thoracic Injuries
Fasting
Serum
Ghrelin Receptor
Gastroparesis
Neurons
Fourth Ventricle
Gastric Emptying
Cholecystokinin
Wounds and Injuries
Patch-Clamp Techniques
Brain Stem
Reflex
Meals
Eating

All Science Journal Classification (ASJC) codes

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

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title = "Diminished gastric prokinetic response to ghrelin in a rat model of spinal cord injury",
abstract = "Background: Patients with cervical or high-thoracic spinal cord injury (SCI) often present reduced gastric emptying and early satiety. Ghrelin provokes motility via gastric vagal neurocircuitry and ghrelin receptor agonists offer a therapeutic option for gastroparesis. We have previously shown that experimental high-thoracic injury (T3-SCI) diminishes sensitivity to another gastrointestinal peptide, cholecystokinin. This study tests the hypothesis that T3-SCI impairs the vagally mediated response to ghrelin. Methods: We investigated ghrelin sensitivity in control and T3-SCI rats at 3-days or 3-weeks after injury utilizing: (i) acute (3-day post-injury) fasting and post-prandial serum levels of ghrelin; (ii) in vivo gastric reflex recording following intravenous or central brainstem ghrelin; and (iii) in vitro whole cell recording of neurons within the dorsal motor nucleus of the vagus (DMV). Key Results: The 2-day food intake of T3-SCI rats was reduced while fasting serum ghrelin levels were higher than in controls. Intravenous and fourth ventricle ghrelin increased in vivo gastric motility in fasted 3-day control rats but not fasted T3-SCI rats. In vitro recording of DMV neurons from 3-day T3-SCI rats were insensitive to exogenous ghrelin. For each measure, vagal responses returned after 3-weeks. Conclusions and Inferences: Hypophagia accompanying T3-SCI produces a significant and physiologically appropriate elevation in serum ghrelin levels. However, higher ghrelin levels did not translate into increased gastric motility in the acute stage of T3-SCI. We propose that this may reflect diminished sensitivity of peripheral vagal afferents to ghrelin or a reduction in the responsiveness of medullary gastric vagal neurocircuitry following T3-SCI.",
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Diminished gastric prokinetic response to ghrelin in a rat model of spinal cord injury. / Besecker, E. M.; White, A. R.; Holmes, Gregory.

In: Neurogastroenterology and Motility, Vol. 30, No. 4, e13258, 01.04.2018.

Research output: Contribution to journalArticle

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T1 - Diminished gastric prokinetic response to ghrelin in a rat model of spinal cord injury

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AU - White, A. R.

AU - Holmes, Gregory

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