Tumor necrosis factor-α synthesis inhibitor, 3,6′-dithiothalidomide, reverses behavioral impairments induced by minimal traumatic brain injury in mice.

J. Neurochem. (2011) 118, 1032-1042. Abstract Mild traumatic brain injury (mTBI) patients do not show clear structural brain defects and, in general, do not require hospitalization, but frequently suffer from long-lasting cognitive, behavioral and emotional difficulties. Although there is no current effective treatment or cure for mTBI, tumor necrosis factor-alpha (TNF-α), a cytokine fundamental in the systemic inflammatory process, represents a potential drug target. TNF-α levels increase after mTBI and may induce or exacerbate secondary damage to brain tissue. The present study evaluated the efficacy of the experimental TNF-α synthesis inhibitor, 3,6′-dithiothalidomide, on recovery of mice from mTBI in a closed head weight-drop model that induces an acute elevation in brain TNF-α and an impairment in cognitive performance, as assessed by the Y-maze, by novel object recognition and by passive avoidance paradigms at 72 h and 7 days after injury. These impairments were fully ameliorated in mice that received a one time administration of 3,6′-dithiothalidomide at either a low (28 mg/kg) or high (56 mg/kg) dose provided either 1 h prior to injury, or at 1 or 12 h post-injury. Together, these results implicate TNF-α as a drug target for mTBI and suggests that 3,6′-dithiothalidomide may act as a neuroprotective drug to minimize impairment. [ABSTRACT FROM AUTHOR]