Experimental spinal cord injury in rats diminishes vagally-mediated gastric responses to cholecystokinin-8s.
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.


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
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.
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
M
M
Tong
E
E
Qualls-Creekmore
K N
KN
Browning
R A
RA
Travagli
G M
GM
Holmes
D000818:Animals; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018589:Gastroparesis / Q000209:etiology / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008297:Male; D023421:Models, Animal; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017552:Solitary Nucleus / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology*; D013270:Stomach / Q000187:drug effects* / Q000503:physiopathology*; D013904:Thoracic Vertebrae / Q000293:injuries; D014630:Vagus Nerve / Q000503:physiopathology*
D010446:Peptide Fragments; C410885:cholecystokinin 8; D002766:Cholecystokinin