ABSTRACT
Inammation is now recognized as making a major contribution to the patho-etiology of many diseases including diseases of the central nervous system (CNS) such as traumatic brain injury (TBI) (Ransohoff and Brown, 2012). The inammation can be helpful because it clears necrotic and apoptotic cells and other debris. It can also be extremely harmful in that the ood of molecular stimuli of inammation can initiate a repetitive cycle of tissue destruction. Because of the potential harm generated by excessive inammation in the sterile environment of most TBIs, a number of anti-inammatory agents have been tested. The results have been either disappointing or inconclusive to date. Glucocorticoids were used clinically to decrease brain edema but failed in a large clinical trial because of increased mortality (Edwards et al., 2005; Roberts et al., 2004). Also, glucocorticoids were shown to aggravate retrograded memory decits in a TBI model (Chen et al., 2009). Nonsteroidal anti-inammatory drugs produced mixed results in models for TBI with some reports indicating improvements (Kovesdi et al., 2012; Thau Zuchman et al., 2012) but others indicating deleterious effects such as worsened cognitive outcomes (Browne et al., 2006). Strategies to reduce inammation by targeting toll-like receptor (TLR) ligands, TLR receptors, or pro-inammatory cytokines have also proven ineffective (Rivest, 2011).
