Assessment of gut dysfunction in a mouse model of stroke.

Abstract

Stroke is a debilitating disease caused by a restriction of blood flow to the brain, and it contributes to over 10% of all deaths annually. Despite early mortality being primarily attributed to the extent of brain infarction, stroke is associated with various non-neurological medical complications. Bacterial pneumonia is a common cause of death in patients with stroke. In addition, bowel dysfunction, such as constipation and incontinence, occurs in over half of all patients with stroke. Emerging research suggests that the onset of infection after stroke arises as a consequence of gastrointestinal dysfunction; however, the mechanisms involved remain unclear. This study aims to examine the effect of stroke on the neurons of the enteric nervous system and intestinal immune compositions. Using the well-established mouse model of stroke called the middle cerebral artery occlusion (MCAO), the gut of C57BL6/J mice that either underwent sham or stroke surgery was assessed. At 24 hours after stroke onset, we observed significantly reduced gut transit; however, there were no significant changes between the number or size of peristaltic contractions in vivo between the sham-operated and post-stroke group. Visualisation of the myenteric plexus through fluorescent staining revealed selective changes in neuronal populations. Furthermore, we assessed the immune population in the intestine via flow cytometry and revealed that stroke promotes an increase of immune cells in the ileum, more specifically macrophages in both the mucosal and myenteric plexus layer. Depletion of macrophages showed moderate rescue of altered gut transit after stroke suggesting stroke-induced gut dysmotility is accompanied by neural and immune changes. Addressing the mechanisms that drive gut dysfunction after stroke could aid in the identification of novel therapeutic targets to reduce gut-derived infection in patients with stroke and improve their outcome.