Increased intestinal inflammatory response and gut barrier dysfunction in Nrf2-deficient mice after traumatic brain injury

Aim: To explore the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in traumatic brain injury (TBI)-induced intestinal inflammatory response and gut barrier dysfunction in the mice. Methods: Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact-acceleration head injury. We measured nuclear factor kappa B (NF-kappa B) by electrophoretic mobility shift assay (EMSA); tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA); intercellular adhesion molecule-1 (ICAM-1) by immunohistochernistry; intestinal permeability by lactulose/mannitol (L/M) test; plasma endotoxin by chromogenic limulus amebocyte lysate test. Results: Intestinal levels of NF-kappa B, pro-inflammatory cytokines and ICAM-1 in Nrf2 (-/-)-deficient mice were significantly higher compared with Nrf2 (+/+) mice at 24 h after TBI. Furthermore, higher intestinal permeability and plasma level of endotoxin were observed in the Nrf2 (-/-) mice compared with Nrf2 (+/+) mice. Conclusion: Nrf2 plays an important protective role in limiting intestinal inflammatory response and gut barrier dysfunction after TBI. (C) 2008 Elsevier Ltd. All rights reserved.