Colitis‐Induced Neurobehavioral Deficits Following Chronic Brain Injury

Disruptions in the bidirectional communications of the brain‐gut axis are increasingly implicated in the onset and progression of a variety of disorders, diseases and injuries. We previously reported that following experimental traumatic brain injury (TBI) in mice (>28 days), pathogenic bacterial infection exacerbated the TBI‐associated lesion volume and inflammation. The aim of these studies was to determine the effects of experimental colitis on cognitive function following chronic brain injury. Methods Prior to the study, all mice underwent a 3‐week mixed bedding protocol to control for microbiome. Male C576Bl/6 mice were placed in either naïve (anesthetic only), sham (5mm craniotomy over the left parietal bone), or moderate‐to‐severe controlled cortical impact (CCI) groups. At 28 days after injury, cohorts of mice in all groups were treated for 7 days with regular water or 3% DSS in the drinking water to induce colitis (injury) followed by replacement with regular water in all groups for 7 days (recovery). Cohorts of mice in all groups were euthanized at day 7/8 or day 14/15. As indices of inflammation, changes in body weight (daily) as well as colon length (at euthanasia) were determined. At euthanasia, sections of colon were processed for microscopic evaluation of injury [scale of 0–5 where 1 (mild) ‐5 (severe)]. Prior to and following induction of colitis, mice were tested on beam walk (BW), novel object recognition (NOR) and Y‐maze (YM) to assess motor and cognitive function. On day 13, mice were subjected to thermal hyperalgesia (TH) testing, via dynamic hot plate. The study was repeated once. Results DSS significantly decreased body weight and colon length and increased damage scores in all groups in the injury phase (Table 1) and these changes persisted in all DSS groups in the recovery phase (data not shown). Sham‐injury is used commonly as a control for TBI studies but can result in an acute mild brain injury. In both the inflammation and recovery phases, DSS was associated with impaired neurobehavioral deficits in the Sham and CCI groups (Table 2). These changes were similar to CCI+H2O and were not observed in either Sham+H2O or Naïve+DSS groups. TH testing for pain sensitivity during the DSS recovery phase showed no significant differences between any group. Conclusion These data show that Sham injury alone or inflammation of the colon alone (Naïve+DSS) did not induce neurobehavioral deficits. In contrast, colitis induced comparable behavioral outcomes in both Sham+DSS and CCI+DSS mice indicating even mild manipulation of the brain results in chronic neurocognitive deficits. These changes were not linked directly to changes in peripheral pain sensitivity. Thus, these data demonstrate that even mild injury primes the brain for development of neurological deficits in response to gut inflammation. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .