Journal
JOURNAL OF NEUROTRAUMA
Volume 27, Issue 12, Pages 2255-2260Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2010.1372
Keywords
ghrelin; intestinal permeability; tight junctions; traumatic brain injury
Funding
- Inje Research and Scholarship Foundation
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Intestinal barrier breakdown following traumatic brain injury (TBI) is characterized by increased intestinal permeability, leading to bacterial translocation, and inflammation. The hormone ghrelin may prevent intestinal injury and have anti-inflammatory properties. We hypothesized that exogenous ghrelin prevents intestinal injury following TBI. A weight-drop model created severe TBI in three groups of anesthetized Balb/c mice. Group TBI: animals underwent TBI only; Group TBI/ghrelin: animals were given 10 mu g of ghrelin intraperitoneally prior and 1 h following TBI; Group sham: no TBI or ghrelin injection. Intestinal permeability was measured 6 h following TBI by detecting serum levels of FITC-Dextran after injection into the intact ileum. The terminal ileum was harvested for histology, expression of the tight junction protein MLCK and inflammatory cytokine TNF-alpha. Permeability increased in the TBI group compared to the sham group (109.7 +/- 21.8 mu g/mL vs. 32.2 +/- 10.1 mu g/mL; p<0.002). Ghrelin prevented TBI-induced permeability (28.3 +/- 4.2 mu g/mL vs. 109.7 +/- 21.8 mu g/mL; p<0.001). The intestines of the TBI group showed blunting and necrosis of villi compared to the sham group, while ghrelin injection preserved intestinal architecture. Intestinal MLCK increased 73% compared to the sham group (p<0.03). Ghrelin prevented TBI-induced MLCK expression to sham levels. Intestinal TNF-alpha increased following TBI compared to the sham group (46.2 +/- 7.1 pg/mL vs. 24.4 +/- 2.2 pg/mL p<0.001). Ghrelin reduced TNF-a to sham levels (29.2 +/- 5.0 pg/mL; p = NS). We therefore conclude that ghrelin prevents TBI-induced injury, as determined by intestinal permeability, histology, and intestinal levels of TNF-alpha. The mechanism for ghrelin mediating intestinal protection is likely multifactorial, and further studies are needed to delineate these possibilities.
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