Abstract Body: Background: Intestinal immune response plays a detrimental role following a stroke. The objective of this study aims to investigate if cooling the gut can protect the brain against ischemic injury.

Methods: Mice were subjected to 60 min middle cerebral artery occlusion (MCAO) followed by 7 days of reperfusion. The experimental groups were: (i) normothermic group (NT) (n=11); (ii) colon cooling (CC) group (n=13); and (iii) surface cooling (SC) group (n=15). A temperature management catheter was inserted via the rectum into the descending colon to maintain the colon temperature at 37°C (NT group) and at 15°C (CC group), while the esophageal temperature was kept as close to 37°C as possible for both groups. In the SC group, both esophageal and colon temperatures were maintained at the same level as the esophageal temperature in the CC group. Temperature management was initiated at 30 min reperfusion and continued for 3 hours. The regional cerebral blood flow (rCBF) was measured during the peri-MCAO period. Bodyweight, behavioral deficits (nesting, pole test, and Y-maze), and neurological scores were examined daily until the 7-day endpoint. At the endpoint, mice were perfusion-fixed for histopathological analysis.

Results: The rCBF was reduced below 10% of the preischemic level during the entire 60 min MCAO period. It returned to the preischemic level at 10 min post-MCAO but gradually declined to 50% of the preischemic level in CC and SC groups and to 70% in NT group by the end of temperature management. Stroke volume was the smallest in CC, smaller in SC, but the largest in NT group. Bodyweight continuously declined in SC and NT but recovered in CC group post-MCAO. Nest building activity and pole test deficits improved in CC but remained in NT or SC group. Neurological score deficits were recovered in CC, partially recovered in SC, but not recovered in NT group. The mortality rate was the lowest in CC, lower in SC, and the highest in NT group. Stroke volumes and behavioral deficits were significantly reduced in the CC compared to the NT group (p<0.01). Post-MCAO SC tended to reduce stroke injury compared to post-MCAO NT, although this reduction did not reach statistical significance.

Conclusion: Post-MCAO intestinal cooling-induced hypothermia offered enhanced brain protection against stroke, which is superior to that offered by the systemic body surface cooling-induced hypothermia.