Antioxidants attenuate acute toxicity of tumor necrosis factor-alpha induced by brain injury in rat

Tumor necrosis factor-alpha alpha (TNF-alpha) and reactive oxygen species ( ROS) are produced in the brain after traumatic injury and have deleterious effects. In a rat model of closed head injury (CHI), the synthetic antioxid ant from the nitroxide family, Tempol, improved recovery and protected the blood-brain barrier. Similar protection was found after CHI in heat-acclima ted rats, in which the endogenous antioxidants have been shown to be elevat ed after CHI, The present study examined the relationship between TNF-alpha and ROS after CHI, namely, whether after CHI, antioxidants that afforded c erebroprotection also attenuated brain levels of TNF-alpha, Three groups of rats were subjected to CHI: (1) control, nontreated, (2) Tempol-treated, a nd (3) heat-acclimated (30 days at 34 degrees C). Four hours after injury ( time for peak production of TNF-alpha), the activity of TNF-alpha was measu red. Although clinical recovery was facilitated in rats of the two treated groups, TNF-alpha activity was as high as in the traumatized, untreated rat s. Moreover, direct injection of TNF-alpha into mouse brain induced disrupt ion of the blood-brain barrier, indicating its acute harmful effect. This t oxic effect was attenuated by before and after treatment with Tempol, Our r esults support the hypothesis that in vivo antioxidants neutralize TNF-alph a toxicity, probably by interfering with activation of the transcription fa ctor NF-kappa-B.