A similar ERKMEKRaf cascade activation was also observed in our previous studies on TBI induced brain edema. The TBI associated stimula tion in Nogo A might have provided a connection that correlates the MAPK pathway to the TBI induced cytotoxic brain edema. Indomethacin selleck kinase inhibitor administration significantly reduced the intracranial pressure and BBB disrup tion, which may attenuate vasogenic brain edema. The protective effect of indomethacin is speculated not only to reduce the vasogenic edema that results from TBI induced intracranial pressure elevation but also to attenuate cytotoxic edema through the inhibition of the Nogo A MAPK pathway. A large number of studies have indicated that inflamma tion is important to TBI induced secondary damage Inhibitors,Modulators,Libraries to neurons, glia and myelin.

TBI induces the rupture of the BBB and various inflammatory responses, including cytokine release, the accumulation of leukocytes, and acti Inhibitors,Modulators,Libraries vation of macrophages and microglia. Prostan glandin E2 is one of the early inflammatory Inhibitors,Modulators,Libraries mediators released by macrophages. Several studies have demonstrated that PGE2 is significantly elevated in the plasma of traumatized patients and animals and is important for macrophage activation. macrophages may migrate toward the site of injury, secrete toxic cytokines, and thereby cause further neuronal damage. Indomethacin, a non specific cyclooxygenase inhibitor, reduces PGE2 production and elicits a potent anti inflammatory effect. In this study, we found that indo methacin treatment significantly attenuated the TBI induced elevation of hippocampal Nogo A and IL 1B.

Recent studies have indicated that Nogo A receptors are expressed in macrophages in Inhibitors,Modulators,Libraries injured peripheral nerves and in oligodendrocytes of the central nervous system. It is highly possible that indomethacin blocks PGE2 production, which then Inhibitors,Modulators,Libraries attenuates the activation of macrophagemicroglia and further reduces the expression normally of Nogo A and IL 1B release. However, further study is needed to verify and delineate this complex mechanism. Conclusions The results presented here indicate that Nogo A plays an important role in TBI induced IL 1B release and neuronal and axonal damage. By inhibiting Nogo A expression, the systemic delivery of indomethacin can greatly ameliorate the TBI induced IL 1B overload and neuronal damage. Background The enzyme 5 lipoxygenase catalyzes the conversion of arachidonic acid to 5 hydroxyperoxyeicosatetraenoic acid and subsequently to 5 hydroxyeicosatetraenoic acid, which can be then metabolized into different leukotrienes. It is abundantly present in the central nervous system, where its activity is regulated by the presence and availability of another protein, 5LO activating protein.