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Experimental spinal cord injury in rats diminishes vagally‐mediated gastric responses to cholecystokinin‐8s
Author(s) -
Tong M.,
Quallscreekmore E.,
Browning K. N.,
Travagli R. A.,
Holmes G. M.
Publication year - 2011
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2010.01616.x
Subject(s) - cholecystokinin , gastric emptying , endocrinology , spinal cord injury , glutamatergic , medicine , spinal cord , microinjection , gastroparesis , gastrointestinal hormone , neuroscience , anesthesia , neuropeptide , glutamate receptor , stomach , biology , receptor , psychiatry
Background We have shown recently that our model of experimental high‐thoracic spinal cord injury (T3‐SCI) mirrors the gastrointestinal clinical presentation of neurotrauma patients, whereby T3‐SCI animals show diminished gastric emptying and dysmotility. In this study we used cholecystokinin as a model peptide to test the hypothesis that the T3‐SCI induced gastroparesis is due, in part, to an impaired vagally‐mediated response to gastrointestinal peptides. Methods We measured the responses to sulfated cholecystokinin (CCK‐8s) in control and T3‐SCI (3 or 21 days after injury) rats utilizing: (i) c‐ fos expression in the nucleus tractus solitarius (NTS) following peripherally administered CCK‐8s; (ii) in vivo gastric tone and motility following unilateral microinjection of CCK‐8s into the dorsal vagal complex (DVC); and (iii) whole cell recordings of glutamatergic synaptic inputs to NTS neurons. Key Results Our results show that: (i) medullary c‐ fos expression in response to peripheral CCK‐8s was significantly lower in T3‐SCI rats 3 days after the injury, but recovered to control values at 3 weeks post‐SCI, (ii) Unilateral microinjection of CCK‐8s in the DVC induced a profound gastric relaxation in control animals, but did not induce any response in T3‐SCI rats at both 3 and 21 days after SCI, (iii) Perfusion with CCK‐8s increased glutamatergic currents in 55% of NTS neurons from control rats, but failed to induce any response in NTS neurons from T3‐SCI rats. Conclusions & Inferences Our data indicate alterations of vagal responses to CCK‐8s in T3‐SCI rats that may reflect a generalized impairment of gastric vagal neurocircuitry, leading to a reduction of gastric functions after SCI.