(C) 2014 Wiley Periodicals, Inc.”
“A brief restraint experience reduces lordosis behavior in ovariectomized females that have been hormonally primed with estradiol benzoate. The addition of progesterone to the priming prevents the lordosis inhibition. Based on prior studies with an inhibitor of progesterone metabolism, we have implicated the intracellular progesterone receptor, rather than progesterone metabolites, as responsible for this protection. However, the progesterone metabolite, allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one), also prevents lordosis inhibition after restraint. In a prior study, we reported that the progestin receptor antagonist, RU486 (11 beta-(4-dimethylamino)pheny1-17

beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one),

attenuated the effect NCT-501 of allopregnanolone. Because RU486 can also block the glucocorticoid receptor, in the current studies, we evaluated the effect of the progestin receptor antagonist, CDB-4124 (17 alpha-acetoxy-21-methoxy-11 beta-[4-N,N-dimethyaminopheny]-19-norpregna-4,9-dione-3,20-dione), which is relatively devoid of antiglucocorticoid activity. Ovariectomized, Fischer rats were injected with 10 Kg estradiol benzoate. Two days later, rats received either 60 mg/kg CDB-4124 or 20% DMSO/propylene glycol vehicle 1 h before injection with 4 mg/kg allopregnanolone. After a pretest to confirm sexual receptivity, rats were restrained for 5 min and immediately tested for sexual behavior. Lordosis behavior was reduced by the restraint

BI 6727 chemical structure and attenuated by allopregnanolone. Pretreatment with CDB-4124 reduced allopregnanolone’s www.selleckchem.com/products/ag-881.html effect. These findings support prior suggestions that allopreganolone reduces the response to restraint by mechanisms that require activation of the intracellular progesterone receptor. (C) 2014 Elsevier Inc. All rights reserved.”
“Cerebral ischemia initiates various injurious processes including neuroinflammatory responses such as activation of microglia and increases in cytokine and nitric oxide release. Evidence primarily from in vitro studies, indicates that neuroinflammatory effects can be either beneficial or harmful, possibly related to stimulus strength. We investigated using in vivo models, the effect of a mild or substantial cerebral hypoxia-ischemia on: cerebral microglial/macrophage activation (ED1), pro-inflammatory cytokines (tumor necrosis factor-alpha), nitrosative stress (nitrotyrosine) and permanent brain damage. A mild insult produced a transient (1-2 days post) increase in activated microglia/macrophages within subcortical white and not gray matter but transiently increased cytokine or nitrotyrosine expression in cortex and not white matter. There was also prolonged scattered cell death in cortex and white matter over weeks along with loss of myelin/axons and cortical atrophy at 4 weeks post-insult.