Genetic Ablation of Nrf2 Enhances Susceptibility to Acute Lung Injury After Traumatic Brain Injury in Mice

Previous studies have shown that nuclear factor erythrold 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. The present study Investigated the role of Nrf2 in the regulation of traumatic brain Injury (TBI)-induced acute lung Injury (ALI). Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop Impact head injury. Pulmonary capillary permeability (PCP), wet/dry weight ratio, apoptosis, inflammatory cytokines and antioxidant/detoxifying enzymes were measured at 24 h after TBI. Mice lacking Nrf2 were found to be more susceptible to TBI-Induced ALI, as characterized by the higher Increase in PCP, wet/dry weight ratio and alveolar cells apoptosis after TBI. This exacerbation of lung Injury in Nrf2-deficient mice was associated with increased pulmonary mRNA and protein expression of Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6); and with decreased pulmonary mRNA expression and enzymatic activities of antioxidant and detoxifying enzymes Including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferese oil (GST-alpha 1)-as compared with their wild-type Nrf2 (+/+) counterparts after TBI. The results of the present study suggest that Nrf2 reduces TBI-Induced acute lung Injury, possibly by decreasing pulmonary Inflammation and inducing antioxidant and detoxifying enzymes. Exp Biol Med 234:181-189, 2009