Transcription Factor Nrf2 Plays a Pivotal Role in Protection Against Traumatic Brain Injury-Induced Acute Intestinal Mucosal Injury in Mice

• Published in: The Journal of surgical research 2009-12, Vol.157 (2), p.251-260
• Main Authors: Jin, Wei, M.D, Wang, Han-Dong, M.D., Ph.D, Hu, Zhi-gang, M.D, Yan, Wei, M.D, Chen, Gang, M.D, Yin, Hong-Xia, M.D
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Apoptosis - physiology; Biological and medical sciences; Brain Injuries - complications; Brain Injuries - metabolism; Cell Membrane Permeability - physiology; Cytokines - metabolism; Disease Models, Animal; Endotoxins - blood; Female; General aspects; inflammation; Injuries of the nervous system and the skull. Diseases due to physical agents; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Intestinal Mucosa - injuries; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; intestine; Jejunum - injuries; Jejunum - metabolism; Jejunum - pathology; Male; Medical sciences; Mice; Mice, Inbred ICR; Mice, Knockout; Microvilli - pathology; Microvilli - physiology; Microvilli - ultrastructure; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; nuclear factor E2-related factor 2; Organic mental disorders. Neuropsychology; oxidative stress; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; RNA, Messenger - metabolism; Surgery; Traumas. Diseases due to physical agents; traumatic brain injury; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2008.08.003

Background Traumatic brain injury (TBI) can induce an acute intestinal mucosal injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) has a unique role in many physiological stress processes, but its contribution to intestinal mucosal injury after TBI remains to be determined. Materials and Methods Wildtype Nrf2 (+/+) and Nrf2 (–/–) deficient mice were subjected to a moderately severe weight-drop impact head injury. Intestinal mucosal morphological changes, plasma endotoxin, intestinal permeability, apoptosis, inflammatory cytokines, and antioxidant/detoxifying enzymes were measured at 24 hours after TBI. Results Nrf2 deficient mice were found to be more susceptible to TBI-induced acute intestinal mucosal injury, as characterized by the higher increase in gut structure damage, plasma endotoxin, intestinal permeability, and apoptosis after TBI. This exacerbation of intestinal mucosal injury in Nrf2 deficient mice was associated with increased intestinal mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β and interleukin-6, and with decreased intestinal mRNA expression and activity levels of antioxidant and detoxifying enzymes including NAD(P)H: quinone oxidoreductase 1 (NQO1) and glutathione S-transferase α-1 (GST-α1), compared with their wildtype Nrf2 (+/+) counterparts after TBI. Conclusions We show for the first time that mice lacking Nrf2 are more susceptible to TBI-induced acute intestinal mucosal injury. Our data suggests that Nrf2 plays an important role in protecting TBI-induced intestinal mucosal injury, possibly by regulating of inflammatory cytokines and inducing of antioxidant and detoxifying enzymes.