Search

Background: Serum hypoxia-inducible factor 1alpha (HIF-1α) is a key regulator in hypoxic and ischemic brain injury. We determined the relationship between serum HIF-1α levels and long-term prognosis plus severity of intracerebral hemorrhage (ICH).Methods: A total of 97 ICH cases and 97 healthy controls were enrolled. Glasgow Coma Scale (GCS) score and hematoma volume were used to assess hemorrhagic severity. Glasgow Outcome Scale (GOS) score of 1-3 at post-stroke 90 days was defined as a poor outcome.Results: Serum HIF-1α levels of ICH patients were significantly higher than those of healthy controls (median, 218.8 vs 105.4 pg/mL; P<0.001) and were substantially correlated with GCS score (r=-0.485, P<0.001), hematoma volume (r=0.357, P<0.001) and GOS score (r=-0.436, P<0.001). Serum HIF-1α levels >239.4 pg/mL discriminated patients at risk of 90-day poor outcome with sensitivity of 65.9% and specificity of 79.3% (area under the receiver operating characteristic curve, 0.725; 95% confidence interval, 0.625-0.811; P<0.001). Moreover, serum HIF-1α levels >239.4 pg/mL were independently associated with a poor 90-day outcome (odds ratio, 5.133; 95% confidence interval, 1.117-23.593; P=0.036).Conclusion: Serum HIF-1α, in close correlation with hemorrhagic severity and poor 90-day outcome, may serve as a potential prognostic biomarker for ICH. [ABSTRACT FROM AUTHOR]

Background: Brain cortex leptin messenger riboneucleic acid (mRNA) expression and serum leptin level are up-regulated in ischemic mouse brain, as well as in rat brain with traumatic brain injury. Elevated leptin plasma levels predict cerebral hemorrhagic stroke independently of traditional risk factors. The goal of this study was to investigate change in plasma leptin level after intracerebral hemorrhage (ICH) and to evaluate its relation with disease outcome. Methods: Eighty-six patients admitted within 6 hrs after ICH and 30 healthy controls were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7 after ICH. Its concentration was measured by enzyme-linked immunosorbent assay (ELISA). Results: After ICH, plasma leptin level in patients increased during the 6-hour period immediately, peaked in 24 hours, decreased gradually thereafter, and was substantially higher than that in healthy controls during the 7-day period. Plasma leptin levels were highly associated with initial Glasgow coma scores, ICH volumes, presences of intraventricular hemorrhage, and survival rates (all P < 0.05). A multivariate analysis selected plasma leptin level related to plasma C-reactive protein level (standardized coefficient, 0.293; P = 0.003). A multivariate analysis showed baseline plasma leptin level as a good predictor for 1-week mortality (odds ratio, 1.228; 95% confidence interval, 1.070-1.409; P = 0.003). A receiver operating characteristic curve identified that a baseline plasma leptin level greater than 34.1 ng/mL predicted 1-week mortality of patients with 75.0% sensitivity and 85.2% specificity (P < 0.001). Area under curve of GCS score was statistically significantly larger than that of plasma leptin level (P = 0.035), but ICH volume''s area under curve not (P = 0.078). Conclusions: Increased plasma leptin level is found after ICH and may contribute to inflammatory process of ICH, in association with a poor clinical outcome. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Oxymatrine is extracted from the traditional Chinese herb Sophora flavescens Ait, possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, and has been used for the treatment of chronic viral hepatitis and many other diseases. Aims of the study: This study aimed to investigate the effects of oxymatrine on inflammatory response mediated by Toll-like receptor4 (TLR4) and nuclear factor kappa-B (NF-κB), oxidative injury induced by 12/15 lipoxygenase (12/15-LOX), phosphorylated p38 mitogen activated protein kinase (phosphor-p38 MAPK) and cytosolic phospholipase A2 (cPLA2), and neuronal cell apoptosis in rat brain with intracerebral hemorrhage (ICH). Materials and methods: Wistar rats were treated intraperitoneally with 60 or 120mg/kg of oxymatrine daily for 5 days following ICH. The rats were sacrificed at hour 2, 6, 12, 24, 48, 72, and 120 after ICH. The gene expressions of TLR-4 and NF-κB, the levels of TNF-alpha, interleukin-1beta, interleukin-6, 12/15-LOX, phospho-p38 MAPK and cPLA2, and the number of apoptotic neuronal cells in rat brain were determined. Results: Oxymatrine at 120mg/kg significantly suppressed gene expressions of TLR-4 and NF-κB, decreased levels of TNF-alpha, interleukin-1beta and interleukin-6, inhibited synthesis of 12/15-LOX, phospho-p38 MAPK and cPLA2 protein, and mitigated apoptotic neuronal changes following ICH in rat. Conclusion: Oxymatrine at 120mg/kg following ICH inhibits inflammatory responses, oxidative injury, and neuronal cell apoptosis in rats. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Ginkgolide B (GB) is one of the ginkgolides that have been isolated from leaves and root bark of the Chinese tree Ginkgo biloba L. (Ginkgoaceae), and is a specific and potent antagonist of platelet activating factor. There is a large body of data showing that GB possesses a markedly neuroprotective property against ischemia-induced impairment in vivo and in vitro. Recently it has been found that GB can inhibit the inflammation in the rat brain tissues with ischemia/reperfusion injury and in the astrocytes treated with lipopolysaccharide, as well as protect neurons against beta-amyloid 25–35 and ischemia-induced apoptosis. However, there have been few reports on the influence of GB on intracerebral hemorrhage (ICH). This study was to investigate the effects of intraperitoneal GB on neuronal cell apoptosis, inflammatory cytokines and Toll-like receptor4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway after ICH. Materials and methods: Wistar rats obtained an intraperitoneal injection of 5, 10 and 20mg/kg GB after ICH once a day till day 5. Rats were sacrificed by decapitation at hour 2, 6 and 12, as well as day 1, 2, 3 and 5 after ICH. Gene expressions of TLR-4 and NF-κB, concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) as well as number of apoptotic neuronal cells in hemorrhagic rat brain tissues were determined. Results: The administration of 10 and 20mg/kg GB could significantly suppress gene expressions of TLR-4 and NF-κB, lessen concentrations of TNF-α, IL-1β and IL-6 as well as reduce number of apoptotic neuronal cells in hemorrhagic rat brain tissues by Least-significant Difference test (P <0.05), but the administration of 5mg/kg GB not (P >0.05). However, a clear concentration-response relationship was not found. Conclusions: GB may inhibit TLR4/NF-κB-dependent inflammatory responses, and furthermore lessen neuronal cell apoptosis after ICH, which may support the use of G. biloba extracts for the treatment of ICH. [Copyright &y& Elsevier]