Gastric vagal motoneuron function is maintained following experimental spinal cord injury

Abstract

Background: Clinical reports indicate that spinal cord injury (SCI) initiates profound gastric dysfunction. Gastric reflexes involve stimulation of sensory vagal fibers, which engage brainstem circuits that modulate efferent output back to the stomach, thereby completing the vago-vagal reflex. Our recent studies in a rodent model of experimental high thoracic (T3-) SCI suggest that reduced vagal afferent sensitivity to gastrointestinal (GI) stimuli may be responsible for diminished gastric function. Nevertheless, derangements in efferent signals from the dorsal motor nucleus of the vagus (DMV) to the stomach may also account for reduced motility. Methods: We assessed the anatomical, neurophysiological and functional integrity of gastric-projecting DMV neurons in T3-SCI rats using: 1) retrograde labeling of gastric-projecting DMV neurons; 2) whole cell recordings from gastric-projecting neurons of the DMV; and, 3) in vivo measurements of gastric contractions following unilateral microinjection of thyrotropin releasing hormone (TRH) into the DMV. Key Results: Immunohistochemical analysis of gastric-projecting DMV neurons demonstrated no difference between control and T3-SCI rats. Whole cell in vitro recordings showed no alteration in DMV membrane properties and the neuronal morphology of these same, neurobiotin-labeled, DMV neurons were unchanged after T3-SCI with regard to cell size and dendritic arborization. Central microinjection of TRH induced a significant facilitation of gastric contractions in both control and T3-SCI rats and there were no significant dose-dependent differences between groups. Conclusions: Our data suggest that the acute, 3 day to 1 week post-SCI, dysfunction of vagally-mediated gastric reflexes do not include derangements in the efferent DMV motoneurons.

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

“…At 3‐weeks, when the post‐injury progression of the lesion epicenter has relatively stabilized and the lesion boundaries are more clearly defined, the percent area of white matter at the lesion epicenter of 3‐week T3‐SCI rats was significantly reduced in comparison to age‐matched T3‐control animals (11 ± 2% vs 78 ± 1%, respectively; P < .05). These data are comparable to the injury extent reported previously and indicate the severity of our injury model . Therefore, all T3‐SCI rats were included for analysis.…”

“…As with any reflex loop, impairment of afferent and/or efferent signaling can profoundly affect function. The functional integrity of the vagal efferent limb appears unaltered by T3‐SCI in that central stimulation of gastric vagal neurocircuitry by the physiologically relevant neuropeptide thyrotropin releasing hormone (TRH) produced equal levels of gastric contractility in T3‐SCI and control rats . Therefore, reduction in vagally mediated afferent signaling from the GI tract remains as the most likely mechanism for our observed reduction in ghrelin sensitivity (discussed in).…”

“…Whole cell patch clamp recordings from acute (3 day) T3‐SCI and control rats identified no changes in the electrophysiological properties of DMV neurons . To verify that T3‐SCI did not induce any long‐term changes, complete electrophysiological properties were assessed in six control neurons and 5 T3‐SCI neurons.…”

“…These data are comparable to the injury extent reported previously and indicate the severity of our injury model. 14,[41][42][43] Therefore, all T3-SCI rats were included for analysis. At 3 days following surgery, the change in body weight between T3-SCI and control animals was −19.5 ± 2.9 g vs −0.5 ± 2.2 g, respectively.…”

“…Whole cell patch clamp recordings from acute (3 day) T3-SCI and control rats identified no changes in the electrophysiological properties of DMV neurons. 43 To verify that T3-SCI did not induce any long-term changes, complete electrophysiological properties were assessed in six control neurons and 5 T3-SCI neurons. The membrane properties of DMV neurons from control and T3-SCI rats 3-weeks following surgery were assessed under current clamp or voltage clamp conditions as described previously.…”