Abstract
The physiopathology of digestive disorders in patients with spinal cord injury (SCI) remains largely unknown, particularly the involvement of the enteric nervous system (ENS). We aimed in a rat model of chronic thoracic SCI to characterize (1) changes in the neurochemical coding of enteric neurons and their putative consequences upon neuromuscular response, and (2) the inflammatory response of the colon. Ex vivo motility of proximal and distal colon segments of SCI and control (CT) rats were studied in an organ chamber in response to electrical field stimulation (EFS) and bethanechol. Immunohistochemical analysis of proximal and distal segments was performed using antibodies again Hu, neuronal nitric oxide synthase, (nNOS), and choline acetyltransferase. Colonic content of acetylcholine and acetylcholinesterase was measured; messenger RNA (mRNA) expression of inflammatory cytokines was measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR) approaches. Compared with the CT rats, the contractile response to bethanechol was significantly decreased in the proximal colon of SCI rats but not in the distal colon. The proportion of nNOS immunoreactive (IR) neurons was significantly reduced in the proximal but not distal colon of SCI rats. No change in proportion of choline acetyltransferase (ChAT)-IR was reported; the tissue concentration of acetylcholine was significantly decreased in the proximal colon of SCI rats. The expression of tumor necrosis factor alpha (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) was significantly reduced in the proximal and distal colon of SCI rats. This study demonstrates that functional motor and enteric neuroplastic changes affect preferentially the proximal colon compared with the distal colon. The underlying mechanisms and factors responsible for these changes remain to be discovered.
Highlights
Spinal Cord Injury (SCI) causes multiple functional impairments
Under basal condition and with drugs, the area under the curve (AUC) of the response induced during electrical field stimulation (EFS) was comparable between SCI and CT rats in proximal and distal colon (Fig. 1B)
Using a rat model of chronic thoracic SCI, we described a region-specific neurochemical remodeling of the enteric nervous system (ENS) characterized by a significant decrease in the proportion of nitrergic neurons in the proximal but not distal colon compared with CT
Summary
Spinal Cord Injury (SCI) causes multiple functional impairments. The severity and the extent of the deficiencies depend on several factors including the level of injury, the completeness of the injury, and whether or not it is flaccid or spastic.[1,2,3] Bowel dysfunction, known as neurogenic bowel, is one of the most prevalent comorbidities associated with SCI.[4].
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