Gastrointestinal vascular permeability changes following spinal cord injury.

Abstract

Gastrointestinal (GI) dysfunction is observed clinically after spinal cord injury (SCI) and contributes to the diminished long-term quality of life. Our study examined the acute and chronic GI vascular changes that occur following SCI. We demonstrated that the GI vascular tract in SCI mice becomes compromised during the acute phase of injury and persists into the chronic phase of injury. Gastrointestinal vasculature permeability was measured using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) at 48hours, and 2 and 4weeks following contusion spinal cord injury. Angiopoietin-1, a vascular stabilizing protein, was administered intravenously following injury. Intestinal contractile activity assessments were performed following the last imaging session. Our results indicated that a single administration of Ang-1 reduced vascular permeability at 48hours but the effect was only transient. However, when the treatment paradigm was changed from a single administration to multiple administrations of Ang-1 following contusion injury, our DCE MRI data indicated a significant decrease in GI vascular permeability 4weeks after injury compared with vehicle control treated animals. This improved GI vascular permeability was associated with improved sustained intestinal contractile activity. We also demonstrated that Ang-1 reduced the expression of sICAM-1 in the ileum compared with the saline-treated group. We show that the GI vasculature is compromised in the acute and chronic phase of injury following spinal contusion. Our results also indicate that multiple administrations of Ang-1 can attenuate GI vascular permeability, possibly reduce inflammation, and improve sustained agonist-induced contraction compared with saline treatment.