Disturbance of capillary perfusions due to leukocyte adhesion, disseminated intravascular coagulat ion, tissue edema is critical components in the pathophysiology of sepsis. Alterations in brain microcirculation during sepsis are not clearly understood. The aim of this study is to gain an improved understanding of alterations through direct visualization of brain microcirculations in an experimental endotoxemi a using intravital microscopy (IVM). Endotoxemia was induced in Lewis rats with Lipopolysaccharide (LPS, 15 mg/kg i.v.). The dura mater was removed via a cranial window to expose the pial vessels on the brain surface. Using fluorescence dyes, plasma extravasation of pial venous vessels and leukocyte-endothelial interaction were visualized by intravital microscopy 4 h after LPS administration. Plasma cytokine levels of IL1-β, IL-6, IFN-γ, TNF-α and KC/GRO were evaluated after IVM. A sign ificant plasma extravasation of the pial venous vessels was found in endotoxemia rats compared to control animals. In addition , a significantly increased number of leukocytes adherent to the pial venous endothelium was observed in septic animals. Endotoxemia also induced a significant elevation of plasma cytokine levels of IL1-β, IL-6, IFN-γ, TNF-α and KC/GRO. Endotoxemia increased permeability in the brain pial vessels accompanied by an increase of leukocyte-endothelium interactions and an increase of inflammatory cytokines in the plasma., J. Zhou ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Acute renal failure (ARF) is mainly characterized by acute tubular necrosis. No significant change was found for mortality rates over the past few decades despite significant advances in supportive care. In recent years, great effort has been focused on traditional and herbal medicine, which is much less toxic than those agents conventionally used and which is nowadays considered as a novel therapeutic agent for ARF. However, the effect of ginsenosides (GS) administered orally on ARF has not been reported yet and little is known about its cellular and molecular mechanism. The purpose of the study is to investigate the protective effect of ginsenoside in rats with ARF on the changes of tyrosine hydroxylase immunoreactivity (TH-IR) as well as on the involvement of mitogen-activated protein kinases (MAPK) in the locus coeruleus. In our assay, glycerol-induced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced the serum blood urea nitrogen, creatinine level, and lipid peroxidation, restored the GSH level and the normal renal morphology. Immunohistochemistry showed that an obvious increase of TH-IR was further enhanced in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the locus coeruleus. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, and ginsenoside can also activate the brain catecholaminergic neurons in the locus coeruleus. Our future attention will be focused to the question whether there is a correlation between the renal protective effect of ginsenosides against acute renal failure and the activation of tyrosine hydroxylase in the locus coeruleus., H. A. Zhang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Generation of reactive oxygen species significantly contributes to the pathogenesis of acute renal failure (ARF) induced by myoglobin release. Ginsenosides (GS), the principal active ingredients of ginseng, is considered as an extremely good antioxidative composition of Chinese traditional and herbal drugs. The purpose of the present study was to investigate the protective effect of ginsenoside in rats with ARF on the changes of cholinergic nervous system in the kidney as well as on the involvement of mitogen-activated protein kinases (MAPK) in the hypothalamic paraventricular nuclei (PVN). In our assay, glycerolinduced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced lipid peroxidation, restored the superoxide dismutase (SOD) level. Meanwhile, the obvious increase of choline acetyltransferase-immunoreactivity (ChAT-IR) in the proximal convoluted tubular cells (PCT) was observed by immunohistochemistry in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the hypothalamic paraventricular nuclei. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, reduce the renal oxidative stress, and ginsenoside can also activate the cholinergic system in PCT, simultaneously MAPK signal pathway in the PVN was also activated., J. Zhou, H. A. Zhang, Y. Lin, H. M. Liu, Y. M. Cui, Y. Xu, N. Zhao, J. M. Ma, K. Fan, C. L. Jiang., and Obsahuje bibliografii
Whole cell patch-clamp recordings from GABAergic cells of thalamic reticular nucleus (RTN) in thalamocortical slices made from postnatal day 6 (P6) to 10 (P10) were used to investigate the pattern of rebound bursts (RBs) triggered by an injection of hyperpolarizing current into RTN cells. The number of RBs in the RTN and the overlying Na+/K+ spikes changed in an agedependent manner. The generation of RBs depended largely on the amplitude of the after-hyperpolarizations (AHPs). RB patterns in response to hyperpolarizing current injection into relay cells were markedly different from RB patterns in RTN cells with an after-depolarization. GABAA receptor antagonist bicuculline methiodide (BMI) changed burst firing patterns, increasing the duration of RB and decreasing the amplitude of AHP in RTN cells. Furthermore, local puffs of NMDA in the presence of BMI induced RBs. K+ channel blocker 4-aminopyridine partially mimicked the effect of BMI on AHPs. The shapes of RBs were altered by a selective CaMKII inhibitor KN-62, but not by an inactive analog KN-04., X. Wang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy