Transcription factor Nrf2 plays a pivotal role in protection against traumatic brain injury-induced acute intestinal mucosal injury in mice.
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.


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-alpha, interleukin-1beta 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 alpha-1 (GST-alpha1), 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.
Jin
Wei
W
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, PR China.
Wang
Han-Dong
HD
Hu
Zhi-gang
ZG
Yan
Wei
W
Chen
Gang
G
Yin
Hong-Xia
HX
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D007583:Jejunum / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008871:Microvilli / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004731:Endotoxins; D053583:Interleukin-1beta; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha