Targeted intestinal cooling offers superior brain protection in the mouse stroke model

Intestinal immune and inflammatory response plays a detrimental role following a stroke. This study aims to evaluate the brain protective efficacies of a novel intestinal cooling (CC) technique relative to the body surface cooling (SC) and the normothermic (NT) condition in a mouse stroke model.

Mice were randomly assigned to CC (n = 13), SC (n = 15), or NT (n = 11) groups. They underwent 60 min of middle cerebral artery occlusion (MCAO) followed by 7-day reperfusion. Both head and intra-colon temperatures were maintained at 37 °C for 30 min before, during, and 30 min after MCAO. At 30 min reperfusion, a cooling catheter was placed to maintain intra-colon at 37 °C in NT or 13-15 °C in CC. The head temperature was maintained at 37 °C in NT and 30 °C in CC. In SC, both intra-colon and head temperatures were maintained at 30 °C. Cooling lasted 3 h. Bodyweight, behavioral deficits (nesting and pole test), and survival rate were assessed post-MCAO. At day 7 post-MCAO, mice were perfusion-fixed for histopathological analysis.

Post-stroke histopathological brain injury areas and volume were significantly reduced in CC, and appeared reduced though not statistically significant in SC, relative to NT. Compared with NT, body weight, nest building activity, and pole test were all significantly recovered in CC post-MCAO. In SC, only nest building improved significantly, while body weight and pole test showed marginal, nonsignificant trends. Consistent with functional recovery, survival was significantly improved in CC but not in SC, compared with NT.

In a murine model, our novel CC technique successfully achieved targeted intestinal cooling while preserving safe upper-body temperatures necessary for normal cardiopulmonary function. Targeted intestinal cooling provides significant benefits superior to SC and NT, including smaller stroke volume, fewer functional deficits, and lower mortality rates, thus supporting the novel concept that the intestines are potential therapeutic targets for stroke management.