ABSTRACT
OBJECTIVE: To investigate changes of myeloid differentiation factor 2 (MD2) in inflammation-induced pain and acupuncture-mediated analgesia. METHODS: Mice were randomly divided into three groups by a random number table method: saline group (n=16), complete Freund's adjuvant (CFA) group (n=24) and CFA+electroacupuncture (EA) group (n=26). Inflammation-induced pain was modelled by injecting CFA to the plantar surface of the hind paw of mice and EA was applied to bilateral Zusanli (ST 36) to alleviate pain. Only mice in the CFA+EA group received EA treatment (30 min/d for 2 weeks) 24 h after modelling. Mice in the saline and CFA groups received sham EA. von-Frey test and Hargreaves test were used to assess the pain threshold. Brain and spinal tissues were collected for immunofluorescence staining or Western blotting to quantify changes of MD2 expression. RESULTS: CFA successfully induced plantar pain and EA significantly alleviated pain 3 days after modelling (P<0.01). Compared with the CFA group, the number of MD2+/c-fos+ neurons was significantly increased in the dorsal horn of the spinal cord 7 and 14 days after EA, especially in laminae I - IIo (P<0.01). The proportion of double positive cells to the number of c-fos positive cells and the mean fluorescence intensity of MD2 neurons were also significantly increased in laminae I - IIo (P<0.01). Western blotting showed that the level of MD2 was significantly decreased by EA only in the hippocampus on day 7 and 14 (both P<0.01) and no significant changes were observed in the cortex, thalamus, cerebellum, or the brainstem (P<0.05). Fluorescence staining showed significant decrease in the level of MD2 in periagueductal gray (PAG) and locus coeruleus (LC) after CFA injection on day 7 (P<0.01 for PAG, P<0.05 for LC) and EA significantly reversed this decrease (P<0.01 for PAG, P<0.05 for LC). CONCLUSION: The unique changes of MD2 suggest that EA may exert the analgesic effect through modulating neuronal activities of the superficial laminae of the spinal cord and certain regions of the brain.
ABSTRACT
BACKGROUND: Dreaming sometimes occurs during sedation. It has been reported that factors such as different anesthetics, depth of anesthesia, age, sex, and preoperative psychological state may affect dreams. Ciprofol and remimazolam are novel choices for painless endoscopy. Herein, we aimed to investigate dreaming during gastrointestinal endoscopy under propofol, ciprofol, and remimazolam anesthesia respectively. METHODS: This is a prospective, parallel-design double-blind, single-center clinical trial. Three hundred and sixty subjects undergoing elective painless gastroscopy, colonoscopy, or gastroenteroscopy will be enrolled. Eligible subjects will undergo propofol-, ciprofol-, or remimazolam-induced anesthesia to finish the examination. Interviews about the modified Brice questionnaire will be conducted in the recovery room. Incidence of dreaming is set as the primary outcome. Secondary outcomes include type of dreams, improvement of sleep quality, evaluation of patients, incidence of insufficient anesthesia, and intraoperative awareness. Safety outcomes are the incidences of hypotension and hypoxia during examination and adverse events during recovery. DISCUSSION: This study may observe different incidences of dreaming and diverse types of dreams, which might lead to different evaluations to the anesthesia procedure. Based on the coming results, anesthesiologists can make a better medication plan for patients who are going to undergo painless diagnosis and treatment. TRIAL REGISTRATION: This trial was registered at the Chinese Clinical Trial Registry on May 18, 2023 (registration number ChiCTR2300071565).
Subject(s)
Anesthesia , Intraoperative Awareness , Propofol , Humans , Propofol/adverse effects , Prospective Studies , Endoscopy, Gastrointestinal/adverse effects , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Norepinephrine infusion decreases hypotension after spinal anesthesia during cesarean section. This study aimed to compare the efficacy of norepinephrine infusion and ephedrine bolus against post-spinal hypotension in parturients. METHODS: In this double-blinded, randomized controlled clinical trial, parturients scheduled for elective cesarean section were randomly allocated to receive norepinephrine infusion (0.05 µg·kg-1·min-1) just before spinal anesthesia continuing for 30 min or ephedrine bolus (0.15âmg/kg) just before spinal anesthesia. A rescue bolus (5 µg norepinephrine for the norepinephrine group, and 5 mg ephedrine for the ephedrine group) was administered whenever hypotension occurred. Our primary outcome was the incidence of hypotension within 30 min of spinal anesthesia administration. Secondary outcomes included maternal and neonatal outcomes 30 min after spinal block, and neonatal cerebral oxygenation 10 min after birth. RESULTS: In total, 190 patients were enrolled; of these patients, 177 were included in the final analysis. Fewer patients suffered hypotension in the norepinephrine group than in the ephedrine group (29.5% vs. 44.9%, odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.28-0.95, Pâ=â0.034). Moreover, the tachycardia frequency was lower in the norepinephrine group than in the ephedrine group (OR: 0.22, 95% CI: 0.11-0.44, Pâ<â0.001), and patients suffered less nausea and vomiting (OR: 0.28, 95% CI: 0.11-0.70, Pâ=â0.004). There was no difference in Apgar scores and umbilical arterial blood gas analysis between the two groups. However, neonatal cerebral regional saturations were significantly higher after birth in the norepinephrine group than in the ephedrine group (mean difference: 2.0%, 95% CI: 0.55%-3.45%, Pâ=â0.008). CONCLUSION: In patients undergoing elective cesarean section with spinal anesthesia, norepinephrine infusion compared to ephedrine bolus resulted in less hypotension and tachycardia, and exhibited potential neonatal benefits. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02542748; https://clinicaltrials.gov/ct2/show/record/NCT02542748.
Subject(s)
Anesthesia, Spinal , Hypotension , Anesthesia, Spinal/adverse effects , Cesarean Section/adverse effects , Double-Blind Method , Female , Humans , Hypotension/drug therapy , Hypotension/prevention & control , Infant, Newborn , Phenylephrine , Pregnancy , Randomized Controlled Trials as Topic , Vasoconstrictor Agents/therapeutic useABSTRACT
BACKGROUND: Transcutaneous electric acupoint stimulation (TEAS) has shown benefits when used peri-operatively. However, the role of numbers of areas with acupoint stimulation is still unclear. Therefore, we report the protocol of a randomized controlled trial of using TEAS in elderly patients subjected to gastrointestinal surgery, and comparing dual-acupoint and single-acupoint stimulation. METHODS/DESIGN: A multicenter, randomized, controlled, three-arm design, large-scale trial is currently undergoing in four hospitals in China. Three hundred and forty-five participants are randomly assigned to three groups in a 1:1:1 ratio, receiving dual-acupoint TEAS, single-acupoint TEAS, and no stimulation, respectively. The primary outcome is incidence of pulmonary complications at 30 days after surgery. The secondary outcomes include the incidence of pulmonary complications at 3 days after surgery; the all-cause mortality within 30 days and 1 year after surgery; admission to the intensive care unit (ICU) and length of ICU stay within 30 days after surgery; the length of postoperative hospital stay; and medical costs during hospitalization after surgery. DISCUSSION: The result of this trial (which will be available in September 2019) will confirm whether TEAS before and during anesthesia could alleviate the postoperative pulmonary complications after gastrointestinal surgery in elderly patients, and whether dual-acupoint stimulation is more effective than single-acupoint stimulation. TRIALS REGISTRATIONS: ClinicalTrials.gov, ID: NCT03230045 . Registered on 10 July 2017.
Subject(s)
Acupuncture Points , Digestive System Surgical Procedures , Electroacupuncture/methods , Gastrointestinal Tract/surgery , Respiratory Tract Diseases/prevention & control , Age Factors , Aged , China , Digestive System Surgical Procedures/adverse effects , Digestive System Surgical Procedures/economics , Digestive System Surgical Procedures/mortality , Electroacupuncture/adverse effects , Electroacupuncture/economics , Electroacupuncture/mortality , Female , Health Care Costs , Humans , Intensive Care Units , Length of Stay , Male , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Respiratory Tract Diseases/economics , Respiratory Tract Diseases/etiology , Respiratory Tract Diseases/mortality , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA) is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC) function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA). EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG) level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG) can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG)-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.
ABSTRACT
OBJECTIVE: To report the 12-month results of the first human uterus transplantation case using robot-assisted uterine retrieval. This type of transplantation may become a treatment for permanent uterine factor infertility. DESIGN: Case study. SETTING: University hospital. PATIENT(S): A 22-year-old woman with complete müllerian agenesis who underwent a previous surgery for vaginal reconstruction. The live uterine donor was her mother. INTERVENTION(S): The uterus transplantation procedure consisted of robot-assisted uterine procurement, orthotopic replacement and fixation of the retrieved uterus, revascularization, and end-to-side anastomoses of bilateral hypogastric arteries and ovarian-uterine vein to the bilateral external iliac arteries and veins. MAIN OUTCOME MEASURE(S): Data from preoperative investigations, surgery, and follow-up (12 months). RESULT(S): The duration of the donor and recipient surgeries were 6 and 8 hours, 50 minutes, respectively. No immediate perioperative complications occurred in the recipient or donor. The recipient experienced menarche 40 days after transplant surgery, and she has had 12 menstrual cycles since the surgery. No rejection episodes occurred in the recipient. CONCLUSION(S): These results demonstrate the feasibility of live-donor uterine transplantation with a low-dose immunosuppressive protocol and the role of DaVinci robotic assistance during human uterine procurement. CLINICAL TRIAL REGISTRATION NUMBER: XJZT12Z06.
Subject(s)
46, XX Disorders of Sex Development/surgery , Congenital Abnormalities/surgery , Hysterectomy/methods , Mullerian Ducts/abnormalities , Ovary/blood supply , Robotic Surgical Procedures/methods , Uterus/transplantation , Veins/transplantation , Female , Humans , Mullerian Ducts/surgery , Ovary/transplantation , Plastic Surgery Procedures/methods , Treatment Outcome , Young AdultABSTRACT
Our study aims to investigate the effects of the inhalation of subanesthestic doses of sevoflurane combined with oxygen on sepsis. Male Sprague-Dawley rats or Male ICR/Km mice underwent caecal ligation and puncture (CLP) or intraperitoneal injection of lipopolysccharide (LPS) to induce sepsis, while sham rats were used as control. Then, rats were treated with the inhalation of sevoflurane in oxygen; and air or 100% oxygen was used as control. Seven-day survival, lung injury and inflammatory factors were assessed. In this in vitro experiment, we obtained RAW264.7 macrophages and human peripheral blood mononuclear cells (PBMCs) incubated by LPS or plasma from septic patients to explore the NF-κB pathway in the effect of the inhalation of sevoflurane combined with oxygen in sepsis. In this study, we found that the inhalation of 0.5 MAC of sevoflurane in 60% oxygen was the best protocol for protecting against lethality resulting from sepsis and ALI, and there was a time window for these protective effects. We also founded that 0.5 MAC of sevoflurane in 60% oxygen inhibited the nuclear translocation of NF-κB in human PBMCs induced by LPS or plasma from septic patients. The subanesthesia dose sevoflurane in 60% oxygen may reduce sepsis-induced inflammatory responses in animals and in PBMCs, and the inhibition to the activation of the NF-κB pathway may contribute to this protection.
ABSTRACT
BACKGROUND: Sepsis is a major cause of mortality in Intensive Care Units. Anesthetic dose isoflurane and 100% oxygen were proved to be beneficial in sepsis; however, their application in septic patients is limited because long-term hyperoxia may induce oxygen toxicity and anesthetic dose isoflurane has potential adverse consequences. This study was scheduled to find the optimal combination of isoflurane and oxygen in protecting experimental sepsis and its mechanisms. METHODS: The effects of combined therapy with isoflurane and oxygen on lung injury and sepsis were determined in animal models of sepsis induced by cecal ligation and puncture (CLP) or intraperitoneal injection of lipopolysaccharide (LPS) or zymosan. Mouse RAW264.7 cells or human peripheral blood mononuclear cells (PBMCs) were treated by LPS to probe mechanisms. The nuclear factor kappa B (NF-κB) signaling molecules were examined by Western blot and cellular immunohistochemistry. RESULTS: The 0.5 minimum alveolar concentration (MAC) isoflurane in 60% oxygen was the best combination of oxygen and isoflurane for reducing mortality in experimental sepsis induced by CLP, intraperitoneal injection of LPS, or zymosan. The 0.5 MAC isoflurane in 60% oxygen inhibited proinflammatory cytokines in peritoneal lavage fluids (tumor necrosis factor-alpha [TNF-ß]: 149.3 vs. 229.7 pg/ml, interleukin [IL]-1ß: 12.5 vs. 20.6 pg/ml, IL-6: 86.1 vs. 116.1 pg/ml, and high-mobility group protein 1 [HMGB1]: 323.7 vs. 449.3 ng/ml; all P< 0.05) and serum (TNF-ß: 302.7 vs. 450.7 pg/ml, IL-1ß: 51.7 vs. 96.7 pg/ml, IL-6: 390.4 vs. 722.5 pg/ml, and HMGB1: 592.2 vs. 985.4 ng/ml; all P< 0.05) in septic animals. In vitro experiments showed that the 0.5 MAC isoflurane in 60% oxygen reduced inflammatory responses in mouse RAW264.7 cells, after LPS stimulation (all P< 0.05). Suppressed activation of NF-κB pathway was also observed in mouse RAW264.7 macrophages and human PBMCs after LPS stimulation or plasma from septic patients. The 0.5 MAC isoflurane in 60% oxygen also prevented the increases of phospho-IKKß/ß, phospho-IκBß, and phospho-p65 expressions in RAW264.7 macrophages after LPS stimulation (all P< 0.05). CONCLUSION: Combined administration of a sedative dose of isoflurane with 60% oxygen improves survival of septic animals through reducing inflammatory responses.
Subject(s)
Anesthesia/methods , Inflammation/drug therapy , Isoflurane/therapeutic use , Lung Injury/drug therapy , Oxygen/therapeutic use , Sepsis/drug therapy , Sepsis/immunology , Adult , Animals , Blotting, Western , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Female , Humans , Leukocytes, Mononuclear/metabolism , Lipopolysaccharide Receptors/metabolism , Lipopolysaccharides/pharmacology , Lung Injury/immunology , Lung Injury/metabolism , Male , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Peroxidase/metabolism , RAW 264.7 Cells , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: Blood transfusion saves lives but may also increase the risk of injury. The objective of this review was to evaluate the possible adverse effects related to transfusion of red blood cell (RBC) concentrates stored for prolonged periods. DATA SOURCES: The data used in this review were mainly from PubMed articles published in English up to February 2015. STUDY SELECTION: Clinical and basic research articles were selected according to their relevance to this topic. RESULTS: The ex vivo changes to RBC that occur during storage are collectively called storage lesion. It is still inconclusive if transfusion of RBC with storage lesion has clinical relevance. Multiple ongoing prospective randomized controlled trials are aimed to clarify this clinical issue. It was observed that the adverse events related to stored RBC transfusion were prominent in certain patient populations, including trauma, critical care, pediatric, and cardiac surgery patients, which leads to the investigation of underlying mechanisms. It is demonstrated that free hemoglobin toxicity, decreasing of nitric oxide bioavailability, and free iron-induced increasing of inflammation may play an important role in this process. CONCLUSION: It is still unclear whether transfusion of older RBC has adverse effects, and if so, which factors determine such clinical effects. However, considering the magnitude of transfusion and the widespread medical significance, potential preventive strategies should be considered, especially for the susceptible recipients.
Subject(s)
Erythrocyte Transfusion/adverse effects , Blood Preservation/adverse effects , Erythrocytes/metabolism , Erythrocytes/physiology , Humans , Nitric Oxide/metabolism , Time FactorsABSTRACT
OBJECTIVE: To study the role of brain responses to thermal stimulation in outcome prediction of patients in either vegetative or minimally conscious states. METHODS: We performed a prospective study with 22 patients and used functional magnetic resonance imaging (fMRI) and EEG reactivity (EEG-R) tests in conjunction with thermal stimulation. We conducted thermal stimulation on patients by stimulating either their feet (fMRI) or hands (EEEG-R) with warm water (42±2°C). Each patient received a 1-year follow-up. RESULTS: Among the 22 patients, 1 was lost to follow- up, 10 had improved outcomes, and the remaining 11 patients showed no improvement. Thermal stimulation induced three different fMRI brain activation patterns: (1) high-order activation in 4 patients, (2) primary activation in 6 patients, and (3) no activation in 11 patients. Eight of the 10 patients with either high-order or primary activation had an improved outcome. Contrastingly, only 2 of the 11 patients with no activation pattern showed improvement. EEG-R was elicited in 11 patients and 9 of them showed improved outcomes. However, among the 10 patients with no EEG-R, 9 patients did not improve. CONCLUSIONS: Using fMRI and EEG to measure brain responses to thermal stimulation is capable of predicting patient outcomes with a high degree of predictive accuracy. SIGNIFICANCE: Thermal stimulation can be used as an objective and quantifiable somatosensory stimulation mode for clinical EEG-R and fMRI tests.
Subject(s)
Brain/physiopathology , Consciousness Disorders/physiopathology , Adolescent , Adult , Aged , Brain Mapping , Electroencephalography , Female , Hot Temperature , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Physical Stimulation , Prognosis , Prospective Studies , Recovery of Function , Young AdultABSTRACT
BACKGROUND: Sudden cardiac arrest is a leading cause of death worldwide. Three-fourths of cardiac arrest patients die before hospital discharge or experience significant neurological damage. Hydrogen-rich saline, a portable, easily administered, and safe means of delivering hydrogen gas, can exert organ-protective effects through regulating oxidative stress, inflammation, and apoptosis. We designed this study to investigate whether hydrogen-rich saline treatment could improve survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation, and the mechanism responsible for this effect. METHODS: Sprague-Dawley rats were subjected to 8 minutes of cardiac arrest by asphyxia. Different doses of hydrogen-rich saline or normal saline were administered IV at 1 minute before cardiopulmonary resuscitation, followed by injections at 6 and 12 hours after restoration of spontaneous circulation, respectively. We assessed survival, neurological outcome, oxidative stress, inflammation biomarkers, and apoptosis. RESULTS: Hydrogen-rich saline treatment dose dependently improved survival and neurological function after cardiac arrest/resuscitation. Moreover, hydrogen-rich saline treatment dose dependently ameliorated brain injury after cardiac arrest/resuscitation, which was characterized by the increase of survival neurons in hippocampus CA1, reduction of brain edema in cortex and hippocampus, preservation of blood-brain barrier integrity, as well as the decrease of serum S100ß and neuron-specific enolase. Furthermore, we found that the beneficial effects of hydrogen-rich saline treatment were associated with decreased levels of oxidative products (8-iso-prostaglandin F2α and malondialdehyde) and inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, and high-mobility group box protein 1), as well as the increased activity of antioxidant enzymes (superoxide dismutase and catalase) in serum and brain tissues. In addition, hydrogen-rich saline treatment reduced caspase-3 activity in cortex and hippocampus after cardiac arrest/resuscitation. CONCLUSIONS: Hydrogen-rich saline treatment improved survival and neurological outcome after cardiac arrest/resuscitation in rats, which was partially mediated by reducing oxidative stress, inflammation, and apoptosis.
Subject(s)
Brain Injuries/drug therapy , Brain/drug effects , Cardiopulmonary Resuscitation , Fluid Therapy/methods , Heart Arrest/therapy , Hydrogen/administration & dosage , Neuroprotective Agents/administration & dosage , Sodium Chloride/administration & dosage , Administration, Intravenous , Animals , Antioxidants/metabolism , Apoptosis/drug effects , Biomarkers/blood , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/pathology , Brain/metabolism , Brain/pathology , Brain Injuries/blood , Brain Injuries/pathology , Caspase 3/metabolism , Cytokines/blood , Dinoprost/analogs & derivatives , Dinoprost/blood , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Administration Schedule , Heart Arrest/diagnosis , Inflammation Mediators/blood , Male , Malondialdehyde/blood , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Oxidative Stress/drug effects , Phosphopyruvate Hydratase/metabolism , Rats , Rats, Sprague-Dawley , S100 Calcium Binding Protein beta Subunit/blood , Time FactorsABSTRACT
N-myc downstream-regulated gene 2 (Ndrg2) is a newly identified molecule that is mainly expressed in astrocytes within the central nervous system (CNS) and is involved in the proliferation and activation of astrocytes. 17ß-estradiol (E2) is one of the most important circulating hormones, and in the CNS, astrocytes are a target and potential mediator of the action of E2. Our most recent study found that DPN, an estrogen receptor (ER) ß-specific agonist, activated the Ndrg2 promoter and elevated endogenous NDRG2 protein expression in MCF7, HSG and T-47D cells. However, whether E2 regulates Ndrg2 expression in astrocytes remains unknown. Here, we conducted both in vivo and in vitro experiments and found that ERß co-localized with NDRG2 in astrocytes. Furthermore, in primary cultured astrocytes, we demonstrated that E2 up-regulated Ndrg2 mRNA and protein expression in a dose- and time-dependent manner and that the ERß agonist DPN but not the ERα agonist PPT up-regulated Ndrg2 expression. In vivo, we found that in the hippocampus of adult ovariectomized (OVX) female mice, Ndrg2 mRNA and protein expression were significantly decreased compared with those in normal adult female mice. After the OVX mice received continuous subcutaneous injections of 50µg/kg E2, 100µg/kg E2 or the ERß agonist DPN for 10 days, the Ndrg2 expression significantly increased compared with that of the OVX mice. Our results indicate that E2 may affect astrocytes by regulating Ndrg2 expression.
Subject(s)
Astrocytes/metabolism , Estradiol/pharmacology , Estrogens/pharmacology , Proteins/metabolism , Adaptor Proteins, Signal Transducing , Animals , Astrocytes/drug effects , Cells, Cultured , Estrogen Receptor beta/agonists , Estrogen Receptor beta/metabolism , Female , Hippocampus/metabolism , Mice , Mice, Inbred C57BL , RNA, Messenger/metabolism , Up-RegulationABSTRACT
INTRODUCTION: Accurate assessment of prognosis for patients with unresponsive wakefulness syndrome (UWS; formerly vegetative state) may help clinicians and families guide the type and intensity of therapy; however, there is no suitable and accurate means to predict the outcome so far. We aimed to develop a simple bedside scoring system to predict the likelihood of awareness recovery in patients with UWS. METHODS: We prospectively enrolled 56 patients (age range 10 to 73 years) with UWS 3 to 12 weeks post-onset. We collected demographic data and performed neurological, serological and neurophysiological tests at study entry. Each patient received a one year follow-up, during which awareness recovery was assessed by experienced physicians on the basis of clinical criteria. Univariate and multivariable analyses were employed to assess the relationships between predictors and awareness recovery. RESULTS: A total of 56 participants were included in the study; of these, 24 patients recovered awareness, 3 with moderate disabilities, 8 with severe disabilities, 12 were in a minimally conscious state, and 1 died after recovery. During the study, 23 patients remained in UWS and 9 died in UWS. Motor response, type of brain injury, electroencephalogram reactivity, sleep spindles and N20 were shown to be independent predictors for awareness recovery. Based on their coefficients in the model, we assigned these predictors with 1 point each and created a 5-point score for prediction of awareness recovery. The resulting score showed good predictive accuracy in the derivation cohort. The area under the receiver operating characteristic curve for the score was 0.918 with 87.50% sensitivity. CONCLUSION: This simple bedside prognostic score can be used to predict the probability of awareness recovery in UWS, thus provide families and clinicians with useful outcome information.
Subject(s)
Neurophysiological Monitoring/methods , Persistent Vegetative State/classification , Adolescent , Adult , Aged , Brain Injuries/complications , Child , Electroencephalography , Evoked Potentials/physiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Persistent Vegetative State/physiopathology , Phosphopyruvate Hydratase/blood , Predictive Value of Tests , Prognosis , Prospective Studies , ROC Curve , Severity of Illness Index , Young AdultABSTRACT
Estrogen has been shown to have neuroprotective effects in numerous experimental studies involving young and adult animals. However, several clinical trials have found that in aged postmenopausal women who received estrogen replacement therapy, there did not appear to be a reduction in the incidence of stroke. The aim of this study was to investigate the effects of physiological dosages of estrogen on aged female mice subjected to ischemia-reperfusion injury. Adult ovariectomized (OVX) female mice and 22-month-old female mice received daily subcutaneous injections of 100 µg/kg or 300 µg/kg 17ß-estradiol (E2) at the back of the neck for four weeks, and the expression levels of estrogen receptor (ER) α and ß in the cerebral cortex were determined using real-time PCR and Western blotting analyses. To mimic ischemic stroke, the mice received middle cerebral artery occlusion (MCAO) treatment for 1h followed by a 24-h reperfusion period. The mice were then subjected to neurological deficit testing and infarct volume evaluation. The aged mice showed higher neurological deficit scores and larger infarct volumes compared with the adult mice. Both the lower and higher physiological dosages of E2 significantly improved the neurological test scores and decreased the infarct volume in the adult mice; however, E2 showed no neuroprotective effects in the aged mice. Furthermore, the protein expression of ERα and ERß in the cerebral cortex was significantly decreased in the aged mice compared with the adult mice, and this decrease was not rescued by E2 treatment. These results indicate that the down-regulation of ERα and ERß in the cerebral cortex may contribute to the loss of estrogen efficacy against ischemic injury in aged females and may point to new therapies for ischemic stroke in aged postmenopausal women.
Subject(s)
Brain Ischemia/drug therapy , Estradiol/therapeutic use , Estrogens/therapeutic use , Neuroprotective Agents/therapeutic use , Age Factors , Animals , Brain Ischemia/etiology , Brain Ischemia/physiopathology , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Cerebral Infarction/drug therapy , Cerebral Infarction/etiology , Cerebral Infarction/pathology , Estradiol/blood , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Estrogen Replacement Therapy , Estrogens/blood , Female , Infarction, Middle Cerebral Artery/complications , Mice, Inbred C57BL , Neuroprotective Agents/blood , Ovariectomy , PostmenopauseABSTRACT
BACKGROUND: Because neuroprotective effects of estrogen remain controversial, we aimed to investigate the effect of different doses of estradiol (E2) on cerebral ischemia using both in vivo and in vitro experiments. RESULTS: PC12 cells were cultured at physiological (10 nM and 20 nM) or pharmacological (10 µM and 20 µM) dosages of E2 for 24 hours (h). The results of 5-bromodeoxyuridine (Brdu) incorporation and flow cytometric analysis showed that physiological doses of E2 enhanced cell proliferation and pharmacological doses of E2 inhibited cell proliferation. After the cells were exposed to oxygen and glucose deprivation (OGD) for 4 h and reperfusion for 20 h, the results of 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, flow cytometric analysis and Western blot analysis showed that physiological doses of E2 enhanced cell viability, reduced cell apoptosis and decreased the expression of pro-apoptotic protein caspase-3. In contrast, pharmacological doses of E2 decreased cell viability and induced cell apoptosis. In vivo, adult ovariectomized (OVX) female rats received continuous subcutaneous injection of different doses of E2 for 4 weeks. Transient cerebral ischemia was induced for 2 h using the middle cerebral artery occlusion (MCAO) technique, followed by 22 h of reperfusion. The results of Garcia test, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that 6 µg/kg and 20 µg/kg E2 replacement induced an increase in neurological deficit scores, a decrease in the infarct volume and a reduction in the expression of caspase-3 when compared to animals in the OVX group without E2 treatment. However, 50 µg/kg E2 replacement treatment decreased neurological deficit scores, increased the infarct volume and the expression of caspase-3 when compared to animals in the control group and 6 up/kg or 20 µg/kg E2 replacement group. CONCLUSION: We conclude that physiological levels of E2 exhibit neuroprotective effects on cerebral ischemia; whereas, pharmacological or supraphysiological doses of E2 have damaging effects on neurons after cerebral ischemia.
Subject(s)
Brain/drug effects , Estradiol/administration & dosage , Infarction, Middle Cerebral Artery/pathology , Neuroprotective Agents/administration & dosage , Animals , Blotting, Western , Brain/metabolism , Brain/pathology , Brain Ischemia/metabolism , Brain Ischemia/pathology , Caspase 3/analysis , Caspase 3/biosynthesis , Cell Survival/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Flow Cytometry , Infarction, Middle Cerebral Artery/metabolism , Neurons/drug effects , Neurons/metabolism , PC12 Cells , Rats , Rats, Sprague-Dawley , Recovery of Function/drug effects , Reperfusion Injury/metabolism , Reperfusion Injury/pathologyABSTRACT
Vibroacoustic disease, a progressive and systemic disease, mainly involving the central nervous system, is caused by excessive exposure to low-frequency but high-intensity noise generated by various heavy transportations and machineries. Infrasound is a type of low-frequency noise. Our previous studies demonstrated that infrasound at a certain intensity caused neuronal injury in rats but the underlying mechanism(s) is still largely unknown. Here, we showed that glial cell-expressed TRPV4, a Ca(2+)-permeable mechanosensitive channel, mediated infrasound-induced neuronal injury. Among different frequencies and intensities, infrasound at 16 Hz and 130 dB impaired rat learning and memory abilities most severely after 7-14 days exposure, a time during which a prominent loss of hippocampal CA1 neurons was evident. Infrasound also induced significant astrocytic and microglial activation in hippocampal regions following 1- to 7-day exposure, prior to neuronal apoptosis. Moreover, pharmacological inhibition of glial activation in vivo protected against neuronal apoptosis. In vitro, activated glial cell-released proinflammatory cytokines IL-1ß and TNF-α were found to be key factors for this neuronal apoptosis. Importantly, infrasound induced an increase in the expression level of TRPV4 both in vivo and in vitro. Knockdown of TRPV4 expression by siRNA or pharmacological inhibition of TRPV4 in cultured glial cells decreased the levels of IL-1ß and TNF-α, attenuated neuronal apoptosis, and reduced TRPV4-mediated Ca(2+) influx and NF-κB nuclear translocation. Finally, using various antagonists we revealed that calmodulin and protein kinase C signaling pathways were involved in TRPV4-triggered NF-κB activation. Thus, our results provide the first evidence that glial cell-expressed TRPV4 is a potential key factor responsible for infrasound-induced neuronal impairment.
Subject(s)
Behavior, Animal/radiation effects , Neuroglia/radiation effects , Neurons/radiation effects , Sound/adverse effects , TRPV Cation Channels/metabolism , Animals , Apoptosis/radiation effects , Blotting, Western , CA1 Region, Hippocampal/metabolism , CA1 Region, Hippocampal/radiation effects , Immunohistochemistry , In Situ Nick-End Labeling , Male , Maze Learning/radiation effects , Mechanoreceptors/metabolism , Neuroglia/metabolism , Neurons/metabolism , RNA Interference , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , TransfectionABSTRACT
Hemopexin (HPX) is a plasma protein with the strongest binding capacity to heme and widely involved in modulation of a variety of physiological and pathological processes. The main physiological function of HPX is to bind and transport free toxic heme. Recent studies indicate that HPX also plays roles of anti-oxidant, anti-apoptosis, immune regulation and organic protection. In addition, HPX participates in regulation of cell differentiation and extracellular matrix reconstruction. In recent years, a great deal of progress has been made in studies of the mechanisms of HPX protective effects and on possible clinical application. In the past few years, especially, a number of proteomic studies have demonstrated that HPX could be served as positive molecular biomarkers for cancers of lung, liver, kidney, colon, and uterine myoma as well as osteoarthritis. In this review, recent progress in the biochemical characteristics and function of HPX and its possible clinical applications are summarized.
Subject(s)
Heme Oxygenase (Decyclizing) , Heme , Hemopexin/chemistry , Hemopexin/metabolism , HumansABSTRACT
Autophagy, a process for the degradation of protein aggregates and dysfunctional organelles, is required for cellular homeostasis and cell survival in response to stress and is implicated in endogenous protection. Ischemic preconditioning is a brief and nonlethal episode of ischemia, confers protection against subsequent ischemia-reperfusion through the up-regulation of endogenous protective mechanisms. Emerging evidence shows that autophagy is associated with the protective effect of ischemic preconditioning. This review summarizes recent progress in research on the functions and regulations of the autophagy pathway in preconditioning-induced protection and cellular survival.
Subject(s)
Autophagy , Ischemic Preconditioning , Animals , Cell Survival , Humans , Ischemic Preconditioning/methods , Signal TransductionABSTRACT
INTRODUCTION: Adolescent scar contracture kyphoscoliosis is a very rare disease. METHODS AND RESULTS: Here, we present the case of a 21-year-old man who was scalded due to ebullient water when he was 10 years old. Moreover, kyphoscoliosis was found when he was 12 years old and developed rapidly. Thereafter, no management was proposed before his consultation at our center. On examination, kyphoscoliosis was detected in thoracolumbar, the trunk deviated to the right on standing view, extensive contractured scar presented on the right side of the back, abdomen, chest wall, hip, right thighs and armpit anterior, especially in the right flank. A one-stage correction was deemed too risky, we therefore released contractured scar during the first stage with the defect of soft tissue protected by vacuum sealing drainage and then performed skeletal traction with halo and bilateral femoral pins. A reasonable correction was achieved without any neurological deficits 1 month after traction. Next, a second-stage operation was taken to translate a free anterolateral thigh myocutaneous flap to overlay the extensive defect of soft tissue. 1.5 months later, a third posterior segmental pedicle screw instrumented fusion with Smith-Peterson osteotomy between T9 and L2 was performed. Postoperative recovery was uneventful and as there were no complications, he was discharged 10 days after the third surgery. At 2-year follow-up the patient's outcome is excellent with balance and correction of the deformity. CONCLUSION: Based this grand round case and relevant literature, we discuss the different options for the treatment of adolescent scar contracture scoliosis.