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1.
Behav Brain Res ; 471: 115068, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38830386

ABSTRACT

Alcohol-Related Brain Damage (ARBD) manifests predominantly as cognitive impairment and brain atrophy with the hippocampus showing particular vulnerability. Fasudil, a Rho kinase (ROCK) inhibitor, has established neuroprotective properties; however, its impact on alcohol-induced cognitive dysfunction and hippocampal structural damage remains unelucidated. This study probes Fasudil's neuroprotective potential and identifies its mechanism of action in an in vivo context. Male C57BL/6 J mice were exposed to 30% (v/v, 6.0 g/kg) ethanol by intragastric administration for four weeks. Concurrently, these mice received a co-treatment with Fasudil through intraperitoneal injections at a dosage of 10 mg/kg/day. Fasudil was found to mitigate alcohol-induced spatial and recognition memory deficits, which were quantified using Y maze, Morris water maze, and novel object recognition tests. Concurrently, Fasudil attenuated hippocampal structural damage prompted by chronic alcohol exposure. Notably, Fasudil moderated alcohol-induced disassembly of the actin cytoskeleton and microtubules-mechanisms central to the maintenance of hippocampal synaptic integrity. Collectively, our findings indicate that Fasudil partially reverses alcohol-induced cognitive and morphological detriments by modulating cytoskeletal dynamics, offering insights into potential therapeutic strategies for ARBD.

2.
BMC Plant Biol ; 24(1): 464, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802756

ABSTRACT

Saline-sodic stress can limit the absorption of available zinc in rice, subsequently impacting the normal photosynthesis and carbohydrate metabolism of rice plants. To investigate the impact of exogenous zinc application on photosynthesis and carbohydrate metabolism in rice grown in saline-sodic soil, this study simulated saline-sodic stress conditions using two rice varieties, 'Changbai 9' and 'Tonghe 899', as experimental materials. Rice seedlings at 4 weeks of age underwent various treatments including control (CT), 2 µmol·L-1 zinc treatment alone (Z), 50 mmol·L-1 saline-sodic treatment (S), and 50 mmol·L-1 saline-sodic treatment with 2 µmol·L-1 zinc (Z + S). We utilized JIP-test to analyze the variations in excitation fluorescence and MR820 signal in rice leaves resulting from zinc supplementation under saline-sodic stress, and examined the impact of zinc supplementation on carbohydrate metabolism in both rice leaves and roots under saline-sodic stress. Research shows that zinc increased the chloroplast pigment content, specific energy flow, quantum yield, and performance of active PSII reaction centers (PIABS), as well as the oxidation (VOX) and reduction rate (Vred) of PSI in rice leaves under saline-sodic stress. Additionally, it decreased the relative variable fluorescence (WK and VJ) and quantum energy dissipation yield (φDO) of the rice. Meanwhile, zinc application can reduce the content of soluble sugars and starch in rice leaves and increasing the starch content in the roots. Therefore, the addition of zinc promotes electron and energy transfer in the rice photosystem under saline-sodic stress. It enhances rice carbohydrate metabolism, improving the rice plants' ability to withstand saline-sodic stress and ultimately promoting rice growth and development.


Subject(s)
Carbohydrate Metabolism , Chlorophyll , Oryza , Seedlings , Zinc , Oryza/metabolism , Oryza/drug effects , Zinc/metabolism , Seedlings/metabolism , Seedlings/drug effects , Carbohydrate Metabolism/drug effects , Chlorophyll/metabolism , Fluorescence , Photosynthesis/drug effects , Plant Leaves/metabolism , Plant Leaves/drug effects
3.
J Mol Neurosci ; 73(4-5): 225-236, 2023 May.
Article in English | MEDLINE | ID: mdl-36930428

ABSTRACT

Posttraumatic stress disorder (PTSD) is a persistent and severe psychological and mental disorder resulting from experiences of serious trauma or stress and is suffered by many individuals. Previous studies have shown that pretreatment with sevoflurane is efficient in reducing the incidence of PTSD. However, we require a more comprehensive understanding of the specific mechanisms by which sevoflurane works. Enhancer of zeste homolog 2 (EZH2) has been reported to be regulated by sevoflurane, and to improve patient cognition. In this study, we aimed to explore the mechanisms of sevoflurane and the role of EZH2 in PTSD cases. We explored the effects of sevoflurane and EPZ-6438 (inhibitor of EZH2) on rat behavior, followed by an investigation of EZH2 mRNA and protein expression. The effects of sevoflurane and EZH2 on neuronal survival were assessed by western blotting and TUNEL staining, while western blotting was used to examine the expression of PSD95 and the AKT/mTOR proteins. Sevoflurane preconditioning restored EZH2 expression and significantly inhibited apoptosis by regulating phosphorylation of the AKT/mTOR pathway. Synaptic plasticity was also significantly improved. These results suggest that pretreatment with sevoflurane could play an important role in PTSD prevention by regulating EZH2 expression.


Subject(s)
Proto-Oncogene Proteins c-akt , Stress Disorders, Post-Traumatic , Rats , Animals , Sevoflurane/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Stress Disorders, Post-Traumatic/drug therapy , Enhancer of Zeste Homolog 2 Protein/genetics , Rats, Sprague-Dawley , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Hippocampus/metabolism , Apoptosis , Neuronal Plasticity
4.
J Clin Med ; 12(3)2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36769799

ABSTRACT

Background: Patients with Crohn's disease (CD) undergoing bowel resection often suffer from depression and acute pain, which severely impairs their recovery. We aimed to investigate the effects of S-ketamine preconditioning on postoperative depression in patients with CD undergoing a bowel resection with mild to moderate depression and to observe whether it can relieve postoperative pain and anti-inflammation. Methods: A total of 124 adult patients were randomized into one of the two groups. Patients in the S-ketamine group received a 0.25 mg/kg S-ketamine intravenous drip under general anesthesia induction, followed by a continuous infusion of S-ketamine with 0.12 mg/kg/h for more than 30 min through target-controlled infusion. Patients in the placebo group received 0.9% saline at an identical volume and rate. The primary outcome measure was the 17-item Hamilton depression Scale (HAMD-17). The secondary outcomes were scores on the following questionnaires: a nine-item patient health questionnaire (PHQ-9); a quality of recovery (QoR-15) form; and a numeric rating scale (NRS). Additional secondary outcomes included the levels of C-reactive protein (CRP) and interleukin 6 (IL-6) on postoperative days (PODs) 1, 3, and 5, the length of hospital stay, and opioid use throughout the hospital stay. Results: The scores of PHQ-9 and HAMD-17 in the S-ketamine group were lower than those in the placebo group on postoperative days (PODs) 1, 2, and 7 (p < 0.05). The scores of QoR-15 in the S-ketamine group were higher than those in the placebo group on postoperative days (PODs) 3 and 5 (p < 0.05). The NRS scores of PACU, postoperative days 1 and 2 in the S-ketamine group were lower than those in the placebo group (p < 0.05). There was no significant difference in the CRP and IL-6 levels on postoperative days (PODs) 1, 3, and 5, postoperative complications, and hospital stay between the two groups (p > 0.05). Conclusions: The trial indicated that the intraoperative administration of low-dose S-ketamine could alleviate mild-to-moderate depressive symptoms and postoperative pain in patients with Crohn's disease undergoing bowel resection without worsening their safety.

5.
Plant Physiol Biochem ; 185: 112-122, 2022 Aug 15.
Article in English | MEDLINE | ID: mdl-35671588

ABSTRACT

The effectiveness of iron is reduced in saline conditions, which can easily lead to iron deficiency and inhibit photosynthesis in rice. In this study, 4-week-old Fe-deficient rice seedlings were treated under saline sodic stress (50 mM) to different concentrations (0, 0.2%, 0.4%, 0.8%, 1.6%, and 3.2%) of foliar iron fertilizer (FeEDDHA). Differences in prompting fluorescence and the MR820 signal of rice leaves after 7 days of treatment were probed using the JIP-test. The results show that the performances of the two rice varieties were in general agreement. Under iron deficiency and soda salinity stress conditions, rice growth was inhibited, and the pigment content, specific energy flux, quantum yield, performance of the active PSII reaction center (PIABS) and the oxidation (Vox) and reduction rates (Vred) of PSI were reduced. These indicators first increase and then decrease with increasing iron fertiliser concentrations. The best results were obtained with the Fe3 treatment (0.8%). Fluorescence parameters such as the relative variable fluorescence (WK and VJ) and the quantum yield of energy dissipation (φDo) showed opposite trends. This suggests that iron deficiency/excess and soda saline stress disrupt the electron and energy transport in the photosystem. Appropriate iron fertilization concentration can repair the photosynthetic electron transport chain, improve electron transport efficiency and promote balanced energy distribution. Therefore, we suggest that moderate amounts of Fe are beneficial for improving the electron and energy transport properties of the photosystem, while spraying high concentrations of Fe fertilizer has a negative effect on improving salt tolerance in rice.


Subject(s)
Iron Deficiencies , Oryza , Chlorophyll , Fertilizers , Fluorescence , Iron/pharmacology , Oryza/metabolism , Photosynthesis , Photosystem II Protein Complex/metabolism , Plant Leaves/metabolism , Seedlings/metabolism
6.
Math Biosci Eng ; 18(6): 9357-9380, 2021 10 27.
Article in English | MEDLINE | ID: mdl-34814349

ABSTRACT

This paper is about the existence of traveling wave solutions for a delayed nonlocal dispersal SIR epidemic model with the critical wave speed. Because of the introduction of nonlocal dispersal and the generality of incidence function, it is difficult to investigate the existence of critical traveling waves. To this end, we construct an auxiliary system and show the existence of traveling waves for the auxiliary system. Employing the results for the auxiliary system, we obtain the existence of traveling waves for the delayed nonlocal dispersal SIR epidemic model with the critical wave speed under mild conditions.


Subject(s)
Epidemics , Models, Biological , Incidence , Travel
7.
Mediators Inflamm ; 2020: 8191079, 2020.
Article in English | MEDLINE | ID: mdl-33061831

ABSTRACT

Disrupted immune response is an important feature of many neurodegenerative conditions, including sepsis-associated cognitive impairment. Accumulating evidence has demonstrated that immune memory occurs in microglia, which has a significant impact on pathological hallmarks of neurological diseases. However, it remains unclear whether immune memory can cause subsequent alterations in the brain immune response and affect neurobehavioral outcomes in sepsis survivors. In the present study, mice received daily intraperitoneal injection of low-dose lipopolysaccharide (LPS, 0.1 mg/kg) for three consecutive days to induce immune memory (immune tolerance) and then were subjected to sham operation or cecal ligation and puncture (CLP) 9 months later, followed by a battery of neurobehavioral and biochemical studies. Here, we showed that repeated low-dose LPS injection-induced immune memory protected mice from sepsis-induced cognitive and affective impairments, which were accompanied by significantly decreased brain proinflammatory cytokines and immune response. In conclusion, our study suggests that modulation of brain immune responses by repeated LPS injections confers neuroprotective effects by preventing overactivated immune response in response to subsequent septic insult.


Subject(s)
Immunity, Innate/physiology , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/immunology , Neuroprotective Agents/immunology , Sepsis/immunology , Animals , Cecum/injuries , Cytokines/blood , Fluorescent Antibody Technique , Ligation/adverse effects , Male , Mice , Mice, Inbred C57BL , Neuroprotective Agents/administration & dosage , Open Field Test , Punctures/adverse effects , Sepsis/blood
8.
Brain Behav Immun ; 89: 133-144, 2020 10.
Article in English | MEDLINE | ID: mdl-32505714

ABSTRACT

Neuroinflammation plays a key role in the progression of many neurodegenerative diseases, yet the underlying mechanism remains largely unexplored. Using an animal model of neuroinflammation induced by repeated lipopolysaccharide (LPS) injections, we found selectively reduced expression of parvalbumin (PV) but not somatostatin (SST) in the medial prefrontal cortex (mPFC). The reduced PV expression resulted in decreased intensities of vesicular GABA transporter and PV buttons, suggesting disinhibition in the mPFC. These further induced abnormal mPFC neural activities and consequently contributed to cognitive impairments. In addition, gamma oscillations supported by PV interneuron function were positively associated with time spent with the novel object in the novel object recognition test. Notably, down-regulation of neuroinflammation by microglia inhibitor minocycline or boosting gamma oscillations by dopamine 4 receptor agonist RO-10-5824 improved cognitive performance. In conclusion, our study proposes neural network disturbance as a likely mechanistic linker between neuroinflammation and cognitive impairments in neurodegeneration and possibly other psychiatric disorders.


Subject(s)
Cognitive Dysfunction , Parvalbumins , Animals , Cognitive Dysfunction/chemically induced , Interneurons/metabolism , Neural Networks, Computer , Parvalbumins/metabolism , Prefrontal Cortex/metabolism
9.
J Card Fail ; 26(10): 885-894, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32105821

ABSTRACT

BACKGROUND: Cognitive dysfunction after heart failure (HF) is characterized by neuroinflammation, which plays an important role in the occurrence and development of cognitive dysfunction. Recent studies have shown that an intestinal flora imbalance may also trigger neuroinflammation in Alzheimer's disease. The present study was designed to reveal that intestinal flora dysbiosis caused by HF aggravates neuroinflammation-associated cognitive impairment. METHODS AND RESULTS: Adult male Sprague-Dawley rats were fed daily for 2 weeks with probiotics or placebo until the day of surgery. HF was then triggered by 8 weeks of sustained coronary artery occlusion. 16S rDNA sequencing was used to confirm intestinal flora dysbiosis after HF and demonstrate that the changes paralleled intestinal pathology scores. The permeability of the blood-brain barrier was increased after HF, and such an increase in permeability may increase the levels of inflammatory cytokines caused by intestinal flora disorders. The changes in the intestinal flora caused by probiotics significantly reduced the level of neuroinflammation. In addition, probiotic administration considerably improved the impaired spatial memory in HF rats. CONCLUSIONS: We conclude that intestinal flora dysbiosis plays a potential role in aggravating the impaired cognition associated with neuroinflammation and that these effects may be attenuated by probiotics.


Subject(s)
Cognitive Dysfunction , Gastrointestinal Microbiome , Heart Failure , Probiotics , Animals , Cognitive Dysfunction/etiology , Dysbiosis/complications , Heart Failure/etiology , Male , Rats , Rats, Sprague-Dawley
11.
Am J Transl Res ; 11(12): 7614-7626, 2019.
Article in English | MEDLINE | ID: mdl-31934305

ABSTRACT

Neuroinflammation plays a key role in the progression and pathogenesis of postoperative cognitive dysfunction, but it does not always occur in the local response to primary injury. In this study, we revealed that probiotics alleviate cognitive dysfunction associated with neuroinflammation in cardiac surgery. Rats were administered a probiotic or placebo once a day by gavage for 2 weeks until the day of surgery. Cardiac surgery was induced by ischemia/reperfusion of the left coronary artery. Key factors, such as the gut microbiome, the gut barrier and the blood-brain barrier (BBB), were systematically investigated to determine whether changes in the gut microbiome lead to neuroinflammation. We used 16S rDNA sequencing to confirm that cardiac surgery induced intestinal flora dysbiosis by altering the number of organisms rather than the structure in the cecum microbiome, which occurs at the same time as damage to the gut barrier. Cardiac surgery also increased BBB permeability, suggesting that disruption of the microbiome may increase the likelihood of neuroinflammation. Probiotics-induced alterations in the intestinal flora significantly reduced the level of inflammatory cytokines (IL-6 and IL-1ß). Importantly, we found that the administration of probiotics significantly improved spatial memory impairment in rats after cardiac surgery, as measured by the Morris water maze. Overall, dysbiosis of the gut flora may aggravate cognitive impairment associated with neuroinflammation after cardiac surgery, and probiotics may attenuate this effect.

12.
BMC Anesthesiol ; 18(1): 130, 2018 09 18.
Article in English | MEDLINE | ID: mdl-30223773

ABSTRACT

BACKGROUND: A right-sided double-lumen tube (R-DLT) tends to obstruct the right upper lobe intraoperatively due to anatomical distortion during surgery. If the R-DLT is poorly matched with the patient's airway anatomy, it will not be possible to correctly replace the tube with a fiberoptic bronchoscope (FOB). In our study, we aimed to explore an efficient method for difficult repositioning caused by right upper lobe occlusion during surgery: repositioning the R-DLT from the right main bronchus into the left main bronchus. The current study was designed to assess the efficacy and safety of this method. METHODS: Sixty adult patients scheduled to undergo left-sided thoracic surgery were randomly assigned to two groups. With the patient in the right lateral position during surgery, the R-DLT was pulled back to the trachea while being rotated 90° clockwise; it was then either rotated 90° clockwise for placement into the left main bronchus (Group L) or rotated 90° anticlockwise and returned to the right main bronchus (Group R) using FOB guidance. The primary outcomes included clinical performance, which was measured by intubation time, and the quality of lung collapse. A secondary outcome was safety, which was determined according to bronchial injury and vocal cord injury. RESULTS: The median intubation time (IQR [range]) required for placement of a R-DLT into the left main bronchus was shorter than the time required for placement into the right main bronchus (15.0 s [IQR, 12.0 to 20.0 s]) vs 23.5 s [IQR, 14.5 to 65.8 s], P = 0.005). The groups showed comparable overall results for the quality of lung collapse during the total period of one-lung ventilation (P = 1.000). The numbers of patients with bronchial injuries or vocal cord injuries were also comparable between groups (Group R, 11/30 vs. Group L 8/30, P = 0.580 for bronchus injuries; Group R, 15/30 vs. Group L 13/30, P = 0.796 for vocal cord injuries). CONCLUSIONS: Repositioning a R-DLT from the right main bronchus into the left main bronchus had good clinical performance without causing additional injury. This may be an efficient method for the difficult repositioning of a R-DLT due to right upper lobe occlusion during surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-15006933 , registered on 15 August 2015.


Subject(s)
Airway Obstruction/prevention & control , Bronchoscopes , Bronchoscopy/instrumentation , Intraoperative Care/methods , Intubation, Intratracheal/instrumentation , Postoperative Complications/prevention & control , Aged , Airway Obstruction/etiology , Bronchoscopes/adverse effects , Bronchoscopes/trends , Bronchoscopy/adverse effects , Bronchoscopy/trends , Female , Hoarseness/etiology , Hoarseness/prevention & control , Humans , Intubation, Intratracheal/adverse effects , Intubation, Intratracheal/trends , Male , Middle Aged , Pharyngitis/etiology , Pharyngitis/prevention & control , Postoperative Complications/etiology , Single-Blind Method
13.
Appl Math Model ; 58: 47-64, 2018 Jun.
Article in English | MEDLINE | ID: mdl-32287942

ABSTRACT

In this paper, we extend the model of Liu and Zhang (Math Comput Model 54:836-845, 2011) by incorporating three control terms and apply optimal control theory to the resulting model. Optimal control strategies are proposed to minimize both the disease burden and the intervention cost. We prove the existence and uniqueness of optimal control paths and obtain these optimal paths analytically using Pontryagin's Maximum Principle. We analyse our results numerically to compare various strategies of proposed controls. It is observed that implementation of three controls is most effective and less expensive among all the strategies. Thus, we conclude that in order to reduce tuberculosis threat all the three controls must be taken into consideration concurrently.

14.
Bound Value Probl ; 2018(1): 42, 2018.
Article in English | MEDLINE | ID: mdl-34171003

ABSTRACT

In this paper, a susceptible-vaccinated-exposed-infectious-recovered (SVEIR) epidemic model for an infectious disease that spreads in the host population through horizontal transmission is investigated, assuming that the horizontal transmission is governed by an unspecified function f ( S , I ) . The role that temporary immunity (vaccinated-induced) and treatment of infected people play in the spread of disease, is incorporated in the model. The basic reproduction number R 0 is found, under certain conditions on the incidence rate and treatment function. It is shown that the model exhibits two equilibria, namely, the disease-free equilibrium and the endemic equilibrium. By constructing a suitable Lyapunov function, it is observed that the global asymptotic stability of the disease-free equilibrium depends on R 0 as well as on the treatment rate. If R 0 > 1 , then the endemic equilibrium is globally asymptotically stable with the help of the Li and Muldowney geometric approach applied to four dimensional systems. Numerical simulations are also presented to illustrate our main results.

15.
Neurochem Res ; 43(2): 420-429, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29168092

ABSTRACT

Oxidative stress caused by mitochondrial dysfunction during reperfusion is a key pathogenic mechanism in cerebral ischemia-reperfusion (IR) injury. Propofol (2,6-diisopropylphenol) has been proven to attenuate mitochondrial dysfunction and reperfusion injury. The current study reveals that propofol decreases oxidative stress injury by preventing succinate accumulation in focal cerebral IR injury. We evaluated whether propofol could attenuate ischemic accumulation of succinate in transient middle cerebral artery occlusion in vivo. By isolating mitochondria from cortical tissue, we also examined the in vitro effects of propofol on succinate dehydrogenase (SDH) activity and various mitochondrial bioenergetic parameters related to oxidative stress injury, such as the production of reactive oxidative species, membrane potential, Ca2+-induced mitochondrial swelling, and morphology via electron microscopy. Propofol significantly decreased the ischemic accumulation of succinate by inhibiting SDH activity and inhibited the oxidation of succinate in mitochondria. Propofol can decrease membrane potential in normal mitochondria but not in ischemic mitochondria. Propofol prevents Ca2+-induced mitochondrial swelling and ultrastructural changes to mitochondria. The protective effect of propofol appears to act, at least in part, by limiting oxidative stress injury by preventing the ischemic accumulation of succinate.


Subject(s)
Ischemia/drug therapy , Oxidative Stress/drug effects , Propofol/pharmacology , Reperfusion Injury/prevention & control , Succinic Acid/pharmacology , Animals , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Ischemia/pathology , Male , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Neuroprotective Agents/pharmacology , Rats, Wistar , Reactive Oxygen Species/metabolism , Reperfusion/methods
16.
J Clin Anesth ; 39: 77-81, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28494914

ABSTRACT

STUDY OBJECTIVE: The purpose of the present study was to investigate whether exogenous melatonin supplementation could ameliorate early postoperative cognitive decline (POCD) in aged patients undergoing hip arthroplasty with spinal anesthesia. DESIGN: Prospective cohort study. SETTING: Department of Anesthesiology, Jinling Hospital, Nanjing University, Nanjing, China. PATIENTS: One hundred and thirty-nine patients with ASA I-III, older than 65yr of age (mean age: 74.5±5.5; gender: male 53 and female 86), scheduled for hip arthroplasty were included in the present study. INTERVENTIONS: Patients were randomized to receive 1mg oral melatonin or placebo daily 1h before bedtime one day before surgery and for another 5 consecutive days postoperatively. MEASUREMENTS: The subject assessment, including Mini-Mental State Examination (MMSE) score, subjective sleep quality, general well-being, postoperative fatigue, and visual analogue scale for pain were evaluated pre-operatively and at days 1, 3, 5, and 7 after surgery. MAIN RESULTS: The MMSE score in the control group decreased significantly after surgery when compared with its own preoperative value or the melatonin group at days 1, 3, and 5. However, the MMSE score in the melatonin group remained unchanged during the 7days of monitoring. In addition, significant postoperative impairments of subjective sleep quality, general well-being, and fatigue were found in the control group when compared with the melatonin group. CONCLUSION: Peroperative melatonin supplementation might improve early POCD, suggesting restoration of normal circadian function with good sleep quality may be one of the key factors in preventing or treating POCD.


Subject(s)
Arthroplasty, Replacement, Hip/methods , Cognitive Dysfunction/prevention & control , Melatonin/administration & dosage , Postoperative Complications/prevention & control , Aged , Aged, 80 and over , Anesthesia, Spinal/methods , China , Circadian Rhythm/drug effects , Cognitive Dysfunction/etiology , Cohort Studies , Fatigue/epidemiology , Female , Follow-Up Studies , Humans , Male , Postoperative Complications/epidemiology , Prospective Studies , Sleep/drug effects , Time Factors
17.
Inflammation ; 40(2): 387-400, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27913953

ABSTRACT

Sepsis-associated encephalopathy (SAE) is a common complication associated with poor prognosis in septic patients, but the underlying mechanism remains unclear. We hypothesized that disturbed neuregulin 1 (NRG1)-ErbB4 signaling in the parvalbumin interneurons was involved in sepsis-induced cognitive impairment in a mouse model of SAE. The SAE model was induced by cecal ligation/perforation (CLP). Animals were randomly divided into the following six groups: sham + vehicle group, sham + NRG1 group, CLP + vehicle group, CLP + NRG1 group, CLP + NRG1 + AG1478 (ErbB4 inhibitor) group, and CLP + minocycline group. Behavioral tests and in vivo electrophysiology were performed at the indicated time points. The brain tissues were harvested to determine the levels of hippocampcal cytokines, IBA1-positive cells, NRG1, ErbB4, and parvalbumin. In the present study, sepsis induced the anxiety-like behavior and hippocampal-dependent cognitive impairment, as reflected by significantly increased distance spent in the open field test and decreased freezing time to context in the fear conditioning test. The abnormal behavioral changes co-occurred with significant increases in hippocampal IBA1-positive cells, IL-1ß and IL-6 levels, and decreased NRG1, ErbB4, parvalbumin expressions, and evoked gamma activity. NRG1 treatment attenuated the sepsis-induced cognitive impairment and the associated biochemical markers, which were abolished by AG1478 administration. Notably, minocycline treatment attenuated neuroinflammation and mimicked the beneficial effects of NRG1 treatment. In summary, we provided additional evidence that the disruption of NRG1-ErbB4 signaling in the parvalbumin interneurons mediated by neuroinflammation might lead to abnormal gamma oscillations and thus contribute to cognitive impairment in a mouse model of SAE.


Subject(s)
Encephalitis/pathology , Hippocampus/metabolism , Hippocampus/physiopathology , Neuregulin-1/metabolism , Receptor, ErbB-4/metabolism , Sepsis-Associated Encephalopathy/physiopathology , Animals , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Disease Models, Animal , Down-Regulation , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Gamma Rhythm , Hippocampus/chemistry , Interneurons/metabolism , Mice , Parvalbumins , Quinazolines/pharmacology , Quinazolines/therapeutic use , Receptor, ErbB-4/antagonists & inhibitors , Signal Transduction/drug effects , Tyrphostins/pharmacology , Tyrphostins/therapeutic use
18.
Oncol Lett ; 11(2): 1398-1400, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26893749

ABSTRACT

A 72-year-old male with a history of prostate cancer and high prostate specific antigen levels underwent 99mtechnetium-methylene diphosphonate (99mTc-MDP) single-photon emission computed tomography/computed tomography (SPECT/CT), to identify bone metastasis. The patient possessed no previous history of serious illnesses or surgical procedures and no family history of malignancies. A whole-body CT scan revealed an intense MDP uptake in the right inguinal region on the anterior view, but not in the posterior view, which was suspected to be a metastatic lesion. However, there was no evidence of bone metastasis on the CT scan. In addition, an increased 99mTc-MDP uptake was indicated on the SPECT images in the right inguinal region, which appeared to be separate from the main bladder activity. CT images of the pelvis revealed an inferior tongue-like extension of the bladder into the right inguinal region. Fused SPECT/CT axial images indicated the circular accumulation of the 99mTc-MDP in the medial right groin, with well-defined walls that connected the accumulation to the bladder. The final diagnosis was a bladder hernia (T2N0M0), which may have been responsible for the misdiagnosis of bone metastasis due to the use of radiopharmaceuticals (99mTc-MDP) that were mainly excreted through urination. Considering the comprehensive situation of the patient, radical prostatectomy was performed. The bladder hernia was subsequently monitored by follow-up examination every 3 months, and remains alive and under follow-up to date.

19.
Injury ; 47(2): 408-12, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26604036

ABSTRACT

PURPOSE: The purpose of the present study was to test whether older red blood cells (RBCs) transfusion results in an increased risk of postoperative delirium (POD) and various in-hospital postoperative complications in elderly patients undergoing hip fracture surgery. MATERIALS AND METHODS: Patients (≥65 years) who underwent hip fracture surgery were enrolled, 179 patients were divided into two groups according to the storage time of the RBCs. The shorter storage time of RBCs transfusion group comprised patients who received RBCs ≤14 days old and the longer storage time of RBCs transfusion group comprised patients who received RBCs >14 days old. The blood samples were collected before anaesthesia induction, 4 and 24 h after RBCs transfusion for the determination of proinflammatory mediators, malondialdehyde, and superoxide dismutase activity. RESULTS: There was no difference in the baseline characteristics, the incidence of POD, and the in-hospital postoperative complications between the shorter storage time of RBCs transfusion group and the longer storage time of RBCs transfusion groups (P>0.05). Compared with the shorter storage time of RBCs transfusion group, the longer storage time of RBCs transfusion caused significantly longer duration of POD (P<0.05). There were significantly increased plasma levels of IL-8 and malondialdehyde at 24 h and IL-1ß at 4 h after RBCs transfusion in the POD group compared with the non-POD group (P<0.05). CONCLUSION: Transfusion of the longer storage RBCs is not associated with a higher incidence of POD or in-hospital postoperative complications, but with longer duration of POD in elderly patients undergoing hip fracture surgery.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Delirium , Erythrocyte Transfusion , Hip Fractures/surgery , Malondialdehyde/blood , Postoperative Complications/psychology , Superoxide Dismutase/blood , Aged , Arthroplasty, Replacement, Hip/psychology , Biomarkers/blood , Delirium/blood , Delirium/etiology , Female , Hemoglobins/analysis , Hip Fractures/complications , Humans , Male , Pilot Projects , Postoperative Complications/blood , Prospective Studies , Time Factors , Treatment Outcome
20.
Mol Med Rep ; 11(4): 3009-14, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25523640

ABSTRACT

Hypothermia is an effective neuroprotective treatment for brain injury caused by intracerebral hemorrhage (ICH). It is reported to reduce brain edema and neuronal cell death. Thrombin, a coagulation protease released from blood clots, is critical in brain edema formation following ICH. Protease activated receptor­1 (PAR­1), matrix metalloproteinase­9 (MMP­9) and aquaporin 4 (AQP4) are edema­associated mediators that have been implicated in ICH pathology. In the present study, thrombin was used to induce brain edema in adult male Sprague­Dawley rats. Differences between a focal mild hypothermic group (33±0.5˚C) and a normothermic group (37˚C) were investigated. Following hypothermia, brain water content and blood­brain barrier (BBB) disruption was assessed at 6, 24 and 48 h and subsequently at 3, 5 and 7 days. At the same time, the mRNA and protein expression of PAR­1, MMP­9 and AQP4 were also determined. It was identified that brain water content and BBB disruption increased at 6 h and reached a maximal level at 24 h in the normothermic group. The mRNA and protein expression levels of PAR­1, MMP­9 and AQP4 started to increase at 24 h and reached a maximal level at 48 h. Focal mild hypothermia tended to significantly reduce brain water content, BBB disruption and PAR­1, MMP­9 and AQP expression at 24 and 48 h. The present data suggest that focal mild hypothermia is an effective treatment for edema formation through moderation of the mRNA and protein expression of PAR­1, MMP­9 and AQP4.


Subject(s)
Aquaporin 4/genetics , Brain Edema/genetics , Gene Expression , Hypothermia, Induced , Matrix Metalloproteinase 9/genetics , Receptor, PAR-1/genetics , Animals , Aquaporin 4/metabolism , Blood-Brain Barrier/metabolism , Brain Edema/chemically induced , Brain Edema/metabolism , Brain Edema/therapy , Disease Models, Animal , Male , Matrix Metalloproteinase 9/metabolism , Permeability , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Receptor, PAR-1/metabolism , Thrombin/adverse effects
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