Alterations of intestinal mucosa structure and barrier function following traumatic brain injury in rats

AIM:Gastrointestinal dysfunction is a common complicationin patients with traumatic brain injury(TBI).However,theeffect of traumatic brain injury on intestinal mucosa has notbeen studied previously.The aim of the current study wasto explore the alterations of intestinal mucosa morphologyand barrier function,and to determine how rapidly theimpairment of gut barrier function occurs and how long itpersists following traumatic brain injury.METHODS:Male Wistar rats were randomly divided intosix groups(6 rats each group)including controls withoutbrain injury and traumatic brain injury groups at hours 3,12,24,and 72,and on day 7.The intestinal mucosa structurewas detected by histopathological examination and electronmicroscopy.Gut barrier dysfunction was evaluated bydetecting serum endotoxin and intestinal permeability.Thelevel of serum endotoxin and intestinal permeability wasmeasured by using chromogenic limulus amebocyte lysateand lactulose/mannitol(L/M)ratio,respectively.RESULTS:After traumatic brain injury,the histopathologicalalterations of gut mucosa occurred rapidly as early as 3hours and progressed to a serious state,including sheddingof epithelial cells,fracture of villi,focal ulcer,fusion ofadjacent villi,dilation of central chyle duct,mucosal atrophy,and vascular dilation,congestion and edema in the villousinterstitium and lamina propria.Apoptosis of epithelial cells,fracture and sparseness of microvilli,loss of tight junctionbetween enterocytes,damage of mitochondria andendoplasm,were found by electron microscopy.The villousheight,crypt depth and surface area in jejunum decreasedprogressively with the time of brain injury.As comparedwith that of control group(183.7±41.8 EU/L),serumendotoxin level was significantly increased at 3,12,and 24hours following TBI(434.8±54.9 EU/L,324.2±61.7 EU/L and303.3±60.2 EU/L,respectively),and peaked at 72 hours(560.5±76.2 EU/L),then declined on day 7(306.7±62.4 EU/L,P<0.01).Two peaks of serum endotoxin level were foundat hours 3 and 72 following TBI.L/M ratio was also significantlyhigher in TBI groups than that in control group(control,0.0172±0.0009;12 h,0.0303±0.0013;24 h,0.0354±0.0025; 72 h,0.0736±0.0105;7 d,0.0588±0.0083;P<0.01).CONCLUSION: Traumatic brain injury can induce significant damages of gut structure and impairment of barrier function which occur rapidly as early as 3 hours following brain injury and lasts for more than 7 days with marked mucosal atrophy.