Background and Purpose-Previously, we showed that 17␤-estradiol (E 2 ) treatment prevented the subarachnoid hemorrhage (SAH)-induced cerebral vasospasm in male rats. The aim of this study was designed to further delineate the molecular mechanisms underlying E 2 -induced inhibition of inducible nitric oxide synthase (iNOS) upregulation and relief of vasospasm caused by SAH. Methods-The 2-hemorrhage SAH model was induced by 2 autologous injections of blood into the cisterna magna of adult male rats. The rats were then subcutaneously implanted of a Silastic tube containing corn oil with or without 17␤-estradiol benzoate and received daily intraperitoneal injections of various doses of ICI 182,780, a nonselective estrogen receptor (ER) antagonist, for 7 days after the first hemorrhage. Basilar arteries were then removed for protein extraction, RNA isolation, and gel mobility assay. The protein levels of iNOS, p65, and ER were examined by Western blot analysis, and that iNOS mRNA expression was evaluated by reverse-transcription polymerase chain reaction. Results-E 2 prevented the SAH-induced vasospasm and increases of the levels of iNOS protein and mRNA in basilar artery through an ER-dependent mechanism. Treatment of the SAH rat with E 2 did not affect the nuclear translocation of p65 subunit of nuclear factor B, but caused an increase of the association of p65/ER, and reversed the SAH-induced increase of the p65 binding on iNOS promoter. Conclusions-E

Background and Purpose-Accumulation of iron after intracerebral hemorrhage causes free radical formation and oxidative damage resulting in liquefaction. The aim of this study was the investigation of molecular mechanisms underlying estrogen-mediated neuroprotective effect against iron-induced brain injury in vivo. Methods-Age-matched male and female Sprague-Dawley rats were stereotaxically infused with either ferrous citrate (FC) or saline (10 L) into the right caudate nucleus. Beta-estradiol 3-benzoate (E 2 ) capsule was implanted subcutaneously at 24 hours before infusion of FC. The severity of brain injury and neurological deficits were measured by histological quantification and forelimb asymmetry test, respectively. The role of thioredoxin (Trx) in E 2 -mediated neuroprotective effect was examined by intrastriatal administration of a Trx reductase inhibitor, 5,5-dithiobis-(2-nitrobenzoic acid), and small interfering RNA. Results-FC induced greater brain injury in male rats than females. E 2 treatment reduced FC-induced brain injury in both sexes. E 2 significantly increased protein level and activity of Trx in the caudate nucleus of females but not males. Administration of female rats with 5,5-dithiobis-(2-nitrobenzoic acid) or Trx small interfering RNA to the caudate nucleus decreased the protective effect of E 2 against FC-induced injury. The protein and mRNA levels of estrogen receptor␣, but not estrogen receptor␤, were more abundant in the caudate nucleus of female rats. Conclusions-Increase of brain Trx activity might play an important role in the E 2 -mediated neuroprotective effect against FC-induced brain injury in female rats. Understanding of the sex differences in the Trx-mediated neuroprotective effect by E 2 might help in improving treatment of brain dysfunction after hemorrhagic stroke and/or head trauma. (Stroke. 2010;41:160-165.)

This study examined the role of exogenous heat shock protein 72 (Hsp72) in reversing sepsis-induced liver dysfunction. Sepsis was induced by cecal ligation and puncture. Liver function was determined on the basis of the enzymatic activities of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT). Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP) protein expressions were analyzed using Western blotting. Results showed GOT and GPT levels increased during sepsis, and levels were restored following the administration of human recombinant Hsp72 (rhHsp72). Increased liver tissue apoptosis was observed during sepsis, and normal apoptosis resumed on rhHsp72 administration. The Bcl-2/Bax ratio, cleaved caspase-3, caspase-9, and PARP protein expressions in the liver tissues were upregulated during sepsis and normalized after rhHsp72 treatment. We conclude that, during sepsis, exogenous Hsp72 restored liver dysfunction by inhibiting apoptosis via the mitochondria-initiated caspase pathway.