Abstract Our study aims to explore whether transplantation of exogenous NSCs could be an effective means to deal with neuronal death. In this study, horseradish peroxidase (HRP) nerve tracing and rat olfactory bulb injury model were established; olfactory function was evaluated; HRP nerve tracing assay was conducted; primary NSCs was prepared, identified, differentiated into astrocytes, and used for treatment SD rats with injured olfactory bulb. Results showed that the foraging time was longer in the disconnected olfactory bulb group than the undisconnected group; HRP nerve tracing showed negative TMB staining in the disconnected olfactory bulb injury site and positive TMB staining in the corresponding undisconnected olfactory bulb site, which confirmed the successful establishment of the rat olfactory bulb disconnected injury model. The primary rat cortical-derived NSCs were confirmed positive by Nestin immunofluorescence staining, and then transplanted to the olfactory nerve of olfactory bulb disconnected rats after Brdu labeling. The foraging time in the NSCs transplanted group was shorter than that in the untransplanted group, and the transplanted NSCs migrated from the olfactory nerve to the site of olfactory bulb injury, showing positive cells for Nestin and Brdu staining in the olfactory bulb anterior nucleus, and a large number of positive cells for GFAP staining in the lateral edge of the olfactory ventricle (olfactory bulb inner sublayer and granular layer, etc.). In this study, we found that transplanted exogenous NSCs exerted a migratory repair effect on olfactory bulb dissociation injury in rats, providing a reference for clinical treatment of olfactory nerve injury.
AIM:To investigate the effects of N-acetylcysteine (NAC) on endoplasmic reticulum (ER) stress and tissue injury during liver ischemia reperfusion injury (IRI). METHODS:Mice were injected with NAC (300 mg/kg) intraperitoneally 2 h before ischemia.Real-time polymerase chain reaction and western blotting determined ER stress molecules (GRP78, ATF4 and CHOP).To analyze the role of NAC in reactive oxygen species (ROS)-mediated ER stress and apoptosis, lactate dehydrogenase (LDH) was examined in cultured hepatocytes treated by H2O2 or thapsigargin (TG).RESULTS: NAC treatment significantly reduced the level of ROS and attenuated ROS-induced liver injury after IRI, based on glutathione, malondialdehyde, serum alanine aminotransferase levels, and histopathology.ROS-mediated ER stress was significantly inhibited in NAC-treated mice.In addition, NAC treatment significantly reduced caspase-3 activity and apoptosis after reperfusion, which correlated with the protein expression of Bcl-2 and Bcl-xl.Similarly, NAC treatment significantly inhibited LDH release from hepatocytes treated by H2O2 or TG. CONCLUSION:This study provides new evidence for the protective effects of NAC treatment on hepatocytes during IRI.Through inhibition of ROS-mediated ER stress, NAC may be critical to inhibit the ER-stressrelated apoptosis pathway.
Objective
To explore the neuroprotective mechanism of minocycline in facial motoneurons by studying the neuroprotective effect of minocycline on expression of glial cell-derived neurotrophic factor (GDNF) in rats after facial nerve ischemia.
Methods
One hundred and twenty male Sprague-Dawley rats were randomly divided into sham-operated (SH) group, petrosal artery interruption (PAI) group and minocyline treated (MC) group (n=40). Facial nerve ischemia models in the later two groups were established by occluding the tympanic segment of the petrosal artery. The rats in MC group were given intragastric injection of minocycline (60 mg/kg) each day, while rats in the PAI and SH groups were given the same amount of normal saline. The animals were executed 3, 7, 14, 28 days after ischemia. The histopathological changes of facial neurons were observed by hematoxylin and eosin (HE) staining. The apoptosis changes in facial motoneurons were detected by Terminal deoxynucleoside transferase mediated-dUTP nick end labeling (TUNEL). The protein expression of GDNF was measured by immunohistochemistry staining and Western blotting.
Results
HE staining results showed that MC group had less severe nerve damage (shrank neuronal somas, condensation of cytoplasm and unconspicuous axon) than PAI group. The TUNEL results showed that the number of apoptotic cells in MC group was significantly fewer than that in PAI group at each time point (P<0.05). Immunohistochemistry and Western blotting indicated increased GDNF protein expression in the PAI group and MC group as compared with that in the SH group, and the GDNF expression in MC group was significantly higher than that in PAI group (P<0.05).
Conclusion
Minocycline could play a strong neuroprotective effect on facial motoneurons of rats after facial nerve ischemia by enhancing GDNF expression and inhibiting facial motoneurons apoptosis.
Key words:
Minocycline; Facial nerve; Ischemia injury; Apoptosis; Glial cell line-derived neurotrophic factor
Abstract Background and purpose Hypertension significantly contributes to stroke. Previous research has indicated a connection between daytime napping and stroke. Research on the connection between daytime napping duration and first stroke in hypertensive individuals is lacking nevertheless. Methods This research, which ran from 24 August 2013 to 31 December 2022, recruited 11,252 individuals with hypertension and without a history of stroke from the China Stroke Primary Prevention Trial. To determine the relationship between daytime napping duration and stroke onset in hypertensive individuals, we conducted analyses for threshold effects, multivariate‐adjusted Cox proportional hazard regression models, and Kaplan–Meier survival curves. Results The duration of daytime napping (<75 min) was positively correlated with stroke risk; beyond 75 min, the risk did not increase further. When compared to hypertensive individuals who napped for 1–30 min, daytime napping 31–60 min (hazard ratio [HR] = 1.27, 95% confidence interval [CI] = 1.06–1.53) and >60 min (HR = 1.37, 95% CI = 1.14–1.65) were substantially related with a greater risk of first stroke. Additionally, this correlation was absent in cases of hemorrhagic stroke, but present in cases of ischemic stroke, specifically for hypertensive individuals who napped for 31–60 min or >60 min ( p < 0.05). Kaplan–Meier survival curves displayed that hypertensive individuals who extended daytime napping had an elevated incidence of stroke. Conclusions Hypertensive individuals who take longer daytime naps (>30 min) are at an elevated risk of stroke onset, particularly ischemic stroke, irrespective of other factors.
Abstract Nitric oxide (NO), a free radical with signaling functions in the CNS, is implicated in some developmental processes, including neuronal survival, precursor proliferation, and differentiation. However, neuronal nitric oxide synthase (nNOS) ‐derived NO and inducible nitric oxide synthase (iNOS) ‐derived NO play opposite role in regulating neurogenesis in the dentate gyrus after cerebral ischemia. In this study, we show that focal cerebral ischemia reduced nNOS expression and enzymatic activity in the hippocampus. Ischemia‐induced cell proliferation in the dentate gyrus was augmented in the null mutant mice lacking nNOS gene (nNOS−/−) and in the rats receiving 7‐nitroindazole, a selective nNOS inhibitor, after stroke. Inhibition of nNOS ameliorated ischemic injury, up‐regulated iNOS expression, and enzymatic activity in the ischemic hippocampus. Inhibition of nNOS increased and iNOS inhibitor decreased cAMP response element‐binding protein phosphorylation in the ipsilateral hippocampus in the late stage of stroke. Moreover, the effects of 7‐nitroindazole on neurogenesis after ischemia disappeared in the null mutant mice lacking iNOS gene (iNOS−/−). These results suggest that reduced nNOS is involved in ischemia‐induced hippocampal neurogenesis by up‐regulating iNOS expression and cAMP response element‐binding protein phosphorylation.
Acute postoperative pain following radical mastectomy is a high risk for prolonged convalescence and potential persistent pain in patients with breast cancer. The present study was designed to observe the effect of intraoperative use of dexmedetomidine on acute postoperative pain following radical mastectomy under general anesthesia. Forty-five patients were enrolled into the study and divided into two groups that were maintained with propofol/remifentanil/Ringer's solution or propofol/remifentanil/Dexmedetomidine followed by morphine-based patient-controlled analgesia. During the first 24 h following surgery, patients receiving dexmedetomine had lower NRS pain scores, decreased morphine consumption, longer time to first morphine request as well as a trending decreased incidence of adverse effects when compared to those received Ringer's solution. In conclusion, the present study finds that intraoperative use of dexmedetomidine could promote analgesic property of postoperative morphine.
Numerous studies have demonstrated that hepatic fibrosis, a progressive condition as an endpoint of multiple chronic hepatic diseases, is largely characterized with the extensive activation of hepatic stellate cells (HSCs). The precise effect of miR-488-5p in HSCs during hepatic fibrosis has not been elucidated.In our study, qRT-PCR was applied to assess the level of miR-488-5p in activated HSCs stimulated by TGF-β1. We built murine liver fibrosis models with carbon tetrachloride (CCl4), high-fat diet (HFD) and bile duct ligation (BDL). In vitro, the effects of miR-488-5p in HSCs were examined through cell proliferation assay and apoptosis. Luciferase reporter assay was applied to identify the underlying target of miR-488-5p. In vivo, the effects of miR-488-5p were explored through mouse liver fibrosis models.The reduction of miR-488-5p in the activated HSCs induced by TGF-β1 and three mouse hepatic fibrosis models were identified. The in vitro functional experimentations verified that miR-488-5p restrained expression of fibrosis-related markers and proliferative capacity in HSCs. Mechanically, we identified that miR-488-5p inhibited tet methylcytosine dioxygenase 3 (TET3) expression via straightly binding onto the 3' UTR of its mRNA, which sequentially restrained the TGF-β/Smad2/3 pathway. TET3 inhibition induced by the overexpression of miR-488-5p reduced extracellular matrix deposition, which contributed to mitigating mouse liver fibrosis.We highlight that miR-488-5p restrains the activation of HSCs and hepatic fibrosis via targeting TET3 which is involved in the TGF-β/Smad2/3 signaling pathway. Collectively, miR-488-5p is identified as a potential therapeutic target for hepatic fibrosis.
Intraoperative dexemdetomidine (DEX) with or without loading dose is well-established to improve postoperative pain control in patient-controlled analgesia (PCA). This study was designed to compare the pro-analgesia effect between the 2 in patients received general anesthesia.Seventy patients shceduced abdominal surgery under general anesthesia were randomly assigned into 3 groups which were maintained using propofol/remifentanil/Ringer solution (PRR), propofol/remifentanil/dexmedetomidine with (PRDw) or without (PRDo) a loading dose of dexmedetomidine before induction.PRDw/o patients displayed a greater Romsay sedation score measured immediately after surgery. When compared with PRR patients, those from the PRDw/o group had an increased time to first request of postoperative morphine and decreased 24 hours total morphine consumption. No significant difference was observed between patients from the PRDw and PRDo groups with respect to these parameters.The present study suggests that the administration of a DEX loading dose does not affect the pro-analgesic effect of intraoperative use of DEX on morphine-based PCA.
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