[Role of extracellular-signal regulated kinase cascade on cerebral ischemia and ischemic preconditioning in hippocampal neuron in gerbils].

AIM: To investigate the role of extracellular-signal regulated kinase (ERK) cascade on cerebral ischemia and ischemic preconditioning in hippocampal neuron. METHODS: Male gerbils were randomly divided into sham group (SH), ischemia/reperfusion group (I/ R), ischemia preconditioning group (IP), specific antagonist of ERK-PD98059 (PD), solvent control groups (VE group), PD98059 combined with IP group (PIP). Forebrain ischemia was induced by occlusion of bilateral common carotid arteries and confirmed by isoelectricity of EEG. Observations were carried out in each group 15 min, 2 h, 4 h, 6 h, 1 d, 3 d, 5 d and 7 d after ischemia. Open field test was used to examine the spontaneous motor activity, the survival and apoptotic neurons, Fos and NF-kappaB masculine neurons in hippocampal CA1 region were counted, the expression of HSP70 in hippocampal CA1 region and p-ERK in hippocampal CA3/DG regions were detected by SABC immunocytochemical technique. RESULTS: The spontaneous motor activity, the number of apoptotic neurons and NF-kappaB masculine neurons at 1 d, 3 d, 5 d, 7 d in CA1 region were much less in IP group than in I/R group (P < 0.01). The number of Fos masculine neurons at 15 min, 2 h, 4 h, 6 h, 1 d in CA1 region were significant more in IP group than in I/R group (P < 0.01). The expressions of p-ERK and HSP70 were significantly higher in IP group than in I/R group. The number of Fos masculine neurons at each point were more and apoptotic neurons at 1 d, 3 d were less in PD group than in I/R group. Results of observation in PIP group were within IP group and I/R group. CONCLUSION: Activation of ERK in CA3/DG regions were related to ischemic tolerance. Induction of the expression of Fos and HSP70, decreasing of the product of NF-kB which might be one of the molecule mechanisms playing an important role in neural protection of ischemic preconditioning.

[Effects of propofol on the changes in cytoskeleton and cellular permeability of human umbilical vascular endothelial cells monolayer induced by lipopolysaccharide].

OBJECTIVE: To investigate the effects of propofol on the changes in actin cytoskeleton and permeability of cultured human umbilical vascular endothelial cells (HUVECs) monolayer induced by lipopolysaccharide (LPS). METHODS: HUVECs were randomly assigned to one of the following seven groups: no additives (negative control), LPS alone (1 mg/L and 10 mg/L), propofol alone (4 mg/L), introlipid alone, LPS (10 mg/L ) combination with propofol (4 mg/L) and LPS (10 mg/L ) together with introlipid (4 mg/L). Changes in filtration coefficients (Kf) and osmotic reflection coefficients (sigma) were measured, and changes in filamentous actin (F-actin) measured by F-actin fluorometry, and expression of nitrotyrosine analyzed by immunocytochemistry were observed in cultured HUVECs. RESULTS: Compared with the control group, the LPS alone group Kf values were significantly increased and the sigma values decreased,the F-actin content was decreased and the expression of nitrotyrosine was increased (all P<0.01), especially in the high dose LPS alone group. The co-treatment of propofol and LPS significantly reduced levels of LPS-enhanced nitrotyrosine protein, and significantly attenuated the changes in Kf and sigma values (all P<0.01), while introlipid group had no such beneficial effects. CONCLUSION: Propofol rather than introlipid, significantly inhibit LPS-induced increase in permeability of HUVECs and alterations in F-actin organization. The scavenging actions of propofol on peroxynitrite may be helpful to attenuate endothelial barrier dysfunction as shown in our current study.

Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, reduces acute lung injury in endotoxemic rats.

OBJECTIVE: Rosiglitazone, a potent agonist of peroxisome proliferator-activated receptor (PPAR)-gamma, exerts anti-inflammatory effects in vitro and in vivo. This study was designated to determine the effects of rosiglitazone on endotoxin-induced acute lung injury in rats. DESIGN: Prospective, experimental study. SETTING: University research laboratory. SUBJECTS: Thirty-six male Wistar rats. INTERVENTIONS: All the animals were randomly assigned to one of six groups (n = 6 per group) and were given either lipopolysaccharide (6 mg/kg intravenously) or saline, pretreated with rosiglitazone (0.3 mg/kg intravenously) or vehicle (10% dimethyl sulphoxide) 30 mins before lipopolysaccharide. The selective PPAR-gamma antagonist GW9662 (0.3 mg/kg intravenously) or its vehicle (10% dimethyl sulphoxide) was given 20 mins before rosiglitazone. MEASUREMENTS AND MAIN RESULTS: Endotoxemia for 4 hrs induced evident lung histologic injury and edema, both of which were significantly attenuated by rosiglitazone pretreatment. The protective effects of rosiglitazone were correlated with the reduction by 71% of the increase of myeloperoxidase activity and the reduction by 84% of the increase of malondialdehyde in the lung tissue. The pulmonary hyperproduction of nitric oxide was reduced by 82% of the increase related to lipopolysaccharide challenge. Pretreatment with rosiglitazone also markedly suppressed lipopolysaccharide-induced expression of inducible nitric oxide synthase messenger RNA and protein in the lung, as demonstrated by reverse transcription-polymerase chain reaction or Western blot analysis. Immunohistochemical analysis revealed that rosiglitazone inhibited the formation of nitrotyrosine, a marker for peroxynitrite reactivity, in the lung tissue. In addition, the specific PPAR-gamma antagonist GW9662 antagonized the effects of rosiglitazone. CONCLUSIONS: This study provides evidence, for the first time, that the PPAR-gamma agonist rosiglitazone significantly reduces endotoxin-induced acute lung injury in rats.

Propofol facilitates the development of long-term depression (LTD) and impairs the maintenance of long-term potentiation (LTP) in the CA1 region of the hippocampus of anesthetized rats.

Memory is sensitive to the short-acting anesthetic (2,6-diisopropylphenol) propofol, but the underlying mechanism is little known. Here, we have examined the effects of propofol on synaptic plasticity in the CA1 region of the hippocampus of anesthetized rats. We found that low dose of propofol (20 mg/kg, i.p.) did not affect the basal transmission, but enhanced prominently the development of long-term depression (LTD) and impaired the maintenance of long-term potentiation (LTP). The impairment of LTP maintenance and enhancement of LTD development may contribute to propofol-induced deficits in memory following propofol anesthesia.