Fig. 1

Experimental timelines. Experimental timeline for cohorts 1, 2, and 3 of mice a. Adult male C57BL/6Nrcl mice arrived at 5 weeks of age. After 1 week of acclimation to the animal facility all mice underwent a 3-week bedding mix protocol following which, at 9 weeks of age, mice underwent either anesthetic exposure only (Naïve), craniotomy (Sham), or craniotomy+controlled cortical impact, CCI (TBI). At 4 weeks following surgery, mice either continued normal drinking water or were administered 3% DSS in drinking water for 7 days to induce intestinal inflammation, followed by a return to normal drinking water for an additional 7 (cohort 2) or 28 (cohort 3) days to recover. Neurobehavioral testing was conducted throughout the study to assess changes in motor function (BW), cognition (MWM, NOR), social behavior (SA), and anxiety-like behavior (MB, LDB). Cohorts 1 and 2 were sacrificed at PTD 35-36 and 42-43, respectively. Cohort 3 underwent all behavioral testing and were sacrificed on PTD 64-68. Colons were collected for morphometric analyses. Blood, spleens, and mesenteric lymph nodes were collected for flow cytometry. Brains from cohorts 1 and 2 were collected for histological analyses. Brains from cohort 3 were dissected into specific subregions for molecular analyses. Additionally, cohort 2 mice underwent ECG for heart rate variability analysis at various timepoints throughout the study to assess changes in autonomic balance b. Abbreviations: BW, beam walk; CCI, controlled cortical impact; DSS, dextran sodium sulfate; ECG, electrocardiography; LDB, light-dark box; MB marble burying; MWM, Morris water maze; NOR, novel object recognition; PTD, post-TBI day; qPCR, quantitative polymerase chain reaction; SA, Crawley’s three-chamber social approach task. Mouse and intestine graphics created with Biorender.com