HSYA (2.5-10 mg/kg) was injected at 1 h after ischemia onset. Other groups received HSYA (10 mg/kg) treatment at 3-9 h after onset. Infarct volume, brain edema, and neurological score were evaluated

8-Bromo-cAMP at 24 h after ischemia. Nitrotyrosine and inducible NO synthase (iNOS) expression, as well as NO level (nitrate/nitrite) in ischemic cortex was examined within 24 h after ischemia. The ability of HSYA to scavenge peroxynitrite was evaluated in vitro.

Infarct volume was significantly decreased by HSYA (P < 0.05), with a therapeutic window of 3 h after ischemia at dose of 10 mg/kg. HSYA treatment also reduced brain edema and improved neurological score (P < 0.05). Nitrotyrosine formation was dose- and time-dependently inhibited by HSYA. The time window of HSYA in decreasing protein tyrosine nitration paralleled its action in infarct volume. HSYA also greatly reduced iNOS expression and NO content at 24 h after ischemia, suggesting prevention of peroxynitrite generation from iNOS. In vitro, HSYA blocked authentic peroxynitrite-induced tyrosine nitration in bovine serum albumin and primary cortical neurons.

Collectively, our results indicated that post-ischemic HSYA treatment attenuates brain ischemic injury which is at least partially due to reducing nitrotyrosine formation, possibly by the combined mechanism of its peroxynitrite scavenging

ability and its reduction in iNOS production. (C) 2013 Elsevier Inc. All rights reserved.”
“In the field of depression, inflammation-associated depression stands up as an exception since its causal factors are obvious and it is easy S63845 to mimic

in an animal model. In addition, quasi-experimental studies can be carried out in patients who are treated chronically with recombinant cytokines for a medical condition since these patients can be studied longitudinally before, during and after stimulation of the immune system. These clinical studies have revealed that depression is a late phenomenon that develops over a background of early appearing sickness. Incorporation of this feature in animal models of inflammation-associated depression has allowed the demonstration that alterations of brain serotoninergic neurotransmission Bambuterol HCl do not play a major role in the pathogenesis. This is in contrast to the activation of the tryptotphan degrading enzyme indoleamine 2,3-dioxygenase that generates potentially neurotoxic kynurenine metabolites such as 3-hydroxy kynurenine and quinolinic acid. Although the relative importance of peripherally versus centrally produced kynurenine and the cellular source of production of this compound remain to be determined, these findings provide new targets for the treatment of inflammation-associated depression that could be extended to other psychiatric conditions mediated by activation of neuroimmune mechanisms. (C) 2010 Elsevier Ltd. All rights reserved.