One of the consequences of traumatic brain injury is an increase in the levels of reactive oxygen species (ROS). These highly reactive molecules contribute to the spread of secondary injury (surrounding the site of primary injury) by destabilizing neuronal membranes, denaturing proteins, and inducing strand breaks in nuclear DNA. In an earlier study we found that pre-treating cultures (4 h) with supplemental quantities of the endogenous antioxidant dihydrolipoic acid (DHLA) resulted in dose-dependent neuroprotection against H2O2-induced oxidative injury. Moreover, the addition of N-tert-butyl-alpha-phenyl nitrone (PBN) to the pre-treatment regimen enhanced the effect of DHLA (Neurotox. Res., in press). While DHLA requires pre-treatment to be neuroprotective, we found that PBN provides more effective neuroprotection when administered post-insult (SFN, 2002). The experiments described here evaluate the efficacy of pre-treating primary neuronal cultures with DHLA, exposing the neurons to an oxidative insult, ...