Stellate Ganglion Block Attenuates LPS-Induced Acute Lung Injury by Activating Sirt3 Regulation of Oxidative Stress and Inflammation.

Stellate ganglion blocks (SGBs) has been applied in clinics to alleviate pain-related syndromes for almost a century. In recent years, it has been reported that SGB can attenuate acute lung injury (ALI) in animals. However, the details of these molecular mechanisms remain complex and unclear. In this study, rats were randomly divided into four groups: group C (receiving no treatment), group NS (receiving the intratracheal instillation of normal saline), group L (receiving the intratracheal instillation of LPS) and group LS (receiving SGB after the intratracheal instillation of LPS). The pathological damage of lung tissue, arterial blood gases, the differentiation of alveolar macrophages (AMs) and inflammatory cytokines (IL-1ß, IL-6, IL-10) were detected. Furthermore, the oxidative stress indexes (ROS, CYP-D, T-SOD, Mn-SOD and CAT) in serum and the levels of Sirt3 signaling-associated proteins (JAK2/STAT3, NF-κb p65, CIRP and NLRP3) in the lungs were measured. The results revealed that SGB could attenuate lung tissue damage, improve pulmonary oxygenation, promote the differentiation of AMs to the M2 phenotype, decrease the secretion of IL-1ß and IL-6, and increase the secretion of IL-10. Meanwhile, SGB was found to inhibit the production of ROS and CYP-D, and enhance the activities of T-SOD, Mn-SOD and CAT. Furthermore, SGB upregulated Sirt3 and downregulated JAK2/STAT3 and NF-κb p65 phosphorylation, CIRP and NLRP3. Our work revealed that SGB could attenuate LPS-induced ALI by activating the Sirt3-mediated regulation of oxidative stress and pulmonary inflammation; this may shed new light upon the protection of SGB and provide a novel prophylactic strategy for LPS-induced ALI.

Exosomes derived from uMSCs promote hair regrowth in alopecia areata through accelerating human hair follicular keratinocyte proliferation and migration.

Alopecia areata (AA) is a complex genetic disease that results in hair loss due to an autoimmune-mediated attack on the hair follicle. Mesenchymal stem cells (MSCs) have great potential to induce hair regeneration due to their strong secretion ability and multidirectional differentiation. Recent studies have revealed that the therapeutic potential of MSCs comes from their secretion ability, which can produce large amounts of bioactive substances and regulate the key physiological functions of subjects. The secretion products of MSCs, such as vesicles, exosomes, and conditioned media, have significant advantages in preparing of biological products derived from stem cells. Human umbilical cord mesenchymal stem cells (uMSCs) are the best choice for exosome production. uMSCs are obtained from the human umbilical cord. The umbilical cord is easy to obtain, and the efficiency of uMSCs isolation and culture higher than that of obtaining MSCs from bone marrow or adipose tissue. In this study, we investigated the effects of exosomes released from uMSCs in AA mice. In summary, due to easy isolation and cultivation, simple preparation, and convenient storage, it is possible to obtain uMSCs, or uMSCs exosomes for research and clinical treatment.

Temporal and Spatial Evolution of Eichmann Lake Wetland in Aksu River Basin and Its Response to Ecological Water Supply.

Timely understanding and quantitative analysis of the changing trend in natural ecosystems in arid and semi-arid areas and their response to the ecological water supply process are of great significance for maintaining the health of oasis ecosystems. Taking the Eichmann Lake wetland of the Aksu River Basin in Xinjiang as the research area, the temporal-spatial distribution characteristics of the lake and the response of ecological water in recent years were studied based on remote sensing images and monitoring data. The results show that: (1) The water surface area of Eichmann Lake is shrinking, from 61.57 km2 in 1996 to 27.76 km2 in 2020. The changes in water surface area have experienced three stages: rapid decline, slow decline, and slow recovery. After the ecological water supply, the water surface area has obvious seasonal changes with hysteresis; (2) In areas with a low average water level, the ecological water supply has a significant impact on the groundwater level. The higher the water supply is, the higher the groundwater level will be. There is a significant lag effect between the change in the groundwater level and the response of the ecological water supply, which is 1-2 months; (3) The response characteristics of different natural vegetation to the ecological water supply were different in interannual, seasonal, and spatial contexts. The response of Populus euphratica to the ecological water supply is obvious, and its growth is the best within the range of 100-500 m from the water supply outlet. This research can provide the basis for the rational allocation of the Aksu River Basin's water resources, and also act as a valuable reference for the restoration and reconstruction of surrounding vegetation in the Aksu River irrigation area.

Ultrasound-guided Multiple Nerve Blocks: A Safe and Effective Anesthetic Modality in Geriatric Hip Fracture Patients.

OBJECTIVES: The aim was to compare the feasibility of ultrasound-guided multiple nerve blocks (fascia iliaca compartment block+sacral plexus block+superior cluneal nerve block) with general anesthesia in geriatric hip fracture patients. METHODS: Ninety-four patients were randomly divided into 2 groups: group N received ultrasound-guided multiple nerve blocks and group G received general anesthesia. Primary outcome measures included perioperative Pain Threshold Index (PTI) and Numerical Rating Scale. Secondary outcome measures comprised the following: (1) perioperative Delirium Index and Short Portable Mental Status Questionnaire; (2) perioperative Comfort Index; (3) perioperative opioid consumption (within 72 hours postoperatively); and (4) postoperative side effects (within 72 h postoperatively). RESULTS: Eighty-seven patients completed the study. Baseline PTI was comparable between the groups. However, intraoperative PTI was significantly lower in group N than in group G. Preoperative and postoperative Comfort Index scores were comparable between the groups. Moderate delirium (24 to 72 h postoperatively) was significantly higher than the baseline in group G. Early moderate delirium (24 h postoperatively) was significantly higher in group G than in group N. Severe delirium was comparable between the groups and within each group. High intraoperative PTI was associated with high opioid consumption. The intravenous sufentanil dose in group G was twice of that in group N. Incidence of nausea and vomiting was similar between the groups. DISCUSSION: Ultrasound-guided multiple nerve blockade may be an alternative to the common anesthetic procedures used for geriatric hip fracture patients. It provided satisfactory intraoperative pain management and reduced early postoperative cognitive disorders.

Demalonylation of DDX3 by Sirtuin 5 promotes antiviral innate immune responses.

Rationale: Hosts defend against viral infection by sensing viral pathogen-associated molecular patterns and activating antiviral innate immunity through TBK1-IRF3 signaling. However, the underlying molecular mechanism remains unclear. Methods: SiRNAs targeting Sirt1-7 were transfected into macrophages to screen the antiviral function. Sirt5 deficient mice or macrophages were subjected to viral infection to assess in vivo and in vitro function of Sirt5 by detecting cytokines, viral replicates and survival rate. Immunoprecipitation, WesternBlot and luciferase reporter assay were used to reveal molecular mechanism. Results: In this study, we functionally screened seven Sirtuin family members, and found that Sirtuin5 (Sirt5) promotes antiviral signaling and responses. Sirt5 deficiency leads to attenuated antiviral innate immunity in vivo and in vitro upon viral infection by decreasing TBK1-IRF3 activation and type I IFN production. Sirt5 overexpression increased antiviral innate immunity. Mechanism investigation revealed that Sirt5 interacts with DDX3 and demalonylates DDX3, which is critical for TBK1-IRF3 activation. Mutation of the demalonylation lysine sites (K66, K130, and K162) of DDX3 increased ifnß transcription. Furthermore, the acetylation on lysine 118 of DDX3 positively regulated ifnß transcription, whereas Sirt5 could not deacetylate this site. Conclusion: Sirt5 promotes anti- RNA and DNA virus innate immune responses by increasing TBK1 signaling through demalonylating DDX3, which identifies a novel regulatory pathway of antiviral innate immune response.

Propofol reduces hypoxia­induced autophagic cell death through downregulating HIF 1α in alveolar epithelial type II cells of rats.

Propofol (2,6­diisopropylphenol) exerts protective effects on alveolar epithelial type II (ATII) cells, partly through attenuating hypoxia­induced apoptosis. Autophagy is involved in the activation of apoptosis. Therefore, the present study investigated the modulating effect of propofol against autophagy in ATII cells under hypoxia. Western blot analysis was performed to detect the protein expression of the autophagy molecular marker, microtubule­associated protein 1 light chain 3 (LC3)­II, under various conditions. The effects of propofol on the accumulation of other autophagy­associated proteins and apoptosis­associated proteins were also determined using western blot analysis. The interactions between proteins were determined by co­immunoprecipitation. Apoptosis of the ATII cells was monitored using FITC­conjugated AV/PI staining. Furthermore, hypoxia­inducible factor 1α (HIF 1α) small interfering (si) RNA was designed to construct si­HIF 1α ATII cells. The efficiency of interference was measured using reverse transcription­quantitative polymerase chain reaction and western blot analyses. Following pre­treatment with propofol, the hypoxia­induced accumulation of LC3­II, HIF 1α and B­cell lymphoma­2 interacting protein 3 (Bnip3) were markedly decreased, accompanied with the activation of mammalian target of rapamycin. In addition, cleaved­poly ADP­ribose polymerase was suppressed, and hypoxia­induced autophagic cell death was inhibited by propofol pre­treatment. HIF 1α was inhibited by si­HIF 1α, which simultaneously suppressed Bnip3 and LC3­II under hypoxia. Taken together, propofol reduced hypoxia­induced autophagic cell death through reducing the expression of HIF 1α in ATII cells, indicating a novel strategy for modulating autophagy via propofol in hypoxic ATII cells.

TLR4-Upregulated IL-1ß and IL-1RI Promote Alveolar Macrophage Pyroptosis and Lung Inflammation through an Autocrine Mechanism.

Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome (MODS) following pulmonary infection. Alveolar macrophages (AM) are at the center of the pathogenesis of the development of ALI. Interleukin-1ß (IL-1ß) is one of the key pro-inflammatory mediators, and its maturation is tightly controlled by the formation and activation of the inflammasome. The biological effects of IL-1ß are mediated through IL-1 receptor (IL-1R). In this study, we investigated the influence of LPS-induced IL-1ß release and IL-1RI upregulation on the development of lung inflammation. We demonstrated that in AM, LPS-TLR4 signaling not only activates Nlrp3 inflammasome activation and subsequent release of IL-1ß, but also up-regulates IL-1RI expression on AM surface through MyD88 and NF-κB dependent signaling. The upregulated IL-1RI, therefore, sensitizes AM to IL-1ß and results in pyroptosome formation, which in turn leads to AM pyroptosis, a type of caspase-1-dependent inflammatory cell death. We further showed that AM pyroptosis exaggerates lung inflammation. The present study demonstrates a novel mechanism underlying LPS-induced innate immunity; that is, a secondary upregulation of IL-1ß-IL-1RI signaling is responsible for AM pyroptosis and augmented lung injury in response to LPS.

Electrical Impedance Tomography-guided PEEP Titration in Patients Undergoing Laparoscopic Abdominal Surgery.

The aim of the study is to utilize electrical impedance tomography (EIT) to guide positive end-expiratory pressure (PEEP) and to optimize oxygenation in patients undergoing laparoscopic abdominal surgery.Fifty patients were randomly assigned to the control (C) group and the EIT (E) group (n = 25 each). We set the fraction of inspired oxygen (FiO2) at 0.30. The PEEP was titrated and increased in a 2-cm H2O stepwise manner, from 6 to 14 cm H2O. Hemodynamic variables, respiratory mechanics, EIT images, analysis of blood gas, and regional cerebral oxygen saturation were recorded. The postoperative pulmonary complications within the first 5 days were also observed.We chose 10 cm H2O and 8 cm H2O as the "ideal" PEEP for the C and the E groups, respectively. EIT-guided PEEP titration led to a more dorsal shift of ventilation. The PaO2/FiO2 ratio in the E group was superior to that in the C group in the pneumoperitoneum period, though the difference was not significant (330 ±â€Š10 vs 305.56 ±â€Š4 mm Hg; P = 0.09). The C group patients experienced 8.7% postoperative pulmonary complications versus 5.3% among the E group patients (relative risk 1.27, 95% confidence interval 0.31-5.3, P = 0.75).Electrical impedance tomography represents a new promising technique that could enable anesthesiologists to assess regional ventilation of the lungs and optimize global oxygenation for patients undergoing laparoscopic abdominal surgery.

Chitosan aerosol inhalation alleviates lipopolysaccharide- induced pulmonary fibrosis in rats.

PURPOSE: Pulmonary fibrosis (PF) is an insidiously progressive scarring disorder of the alveoli and is associated with high mortality. Currently, therapies available are associated with restricted efficacy and side effects. This study aimed to investigate the effect of chitosan aerosol inhalation on lipopolysaccharide (LPS)-induced pulmonary remodeling and fibrosis in rats. METHODS: A rat model of PF was established by intratracheal injection of LPS (5 mg/kg). Chitosan was nebulized to rats from day 4 to 28 after LPS injection. We analyzed the effect of chitosan on LPS-induced pulmonary remodeling and fibrosis by hematoxylin-eosin staining (HE), Masson staining, and the determination of the hydroxyproline content. The expression intensities of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed by western blots. RESULTS: Histological assessments showed that chitosan aerosol inhalation attenuated the fibrotic changes in LPS-induced PF in rats. Compared with the LPS group, the fibrosis parameters were significantly improved in the LPS + chitosan group (LCh group), although not as good as those of the control group. The expressions of MMP-3 and TIMP-1 in the LCh group were markedly less than that of the LPS group on the 28th day. CONCLUSIONS: Our findings show that chitosan aerosol inhalation inhibits the expression of MMP-3 and TIMP-1, and ameliorates LPS-induced pulmonary remodeling and fibrosis in rats.

Dexmedetomidine for the management of awake fibreoptic intubation.

BACKGROUND: Awake fibreoptic intubation (AFOI) frequently requires sedation, anxiolysis and relief of discomfort without impairing ventilation and depressing cardiovascular function. The goal is to allow the patient to be responsive and co-operative. Medications such as fentanyl, remifentanil, midazolam and propofol have been reported to assist AFOI; however,these agents are associated with cardiovascular or respiratory adverse effects. Dexmedetomidine has been proposed as an alternative to facilitate AFOI. OBJECTIVES: The primary objective of this review is to evaluate and compare the efficacy and safety of dexmedetomidine in the management of patients with a difficult or unstable airway undergoing awake fibreoptic intubation (AFOI). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2012, Issue 5), MEDLINE (1966 to May 2012) through Ovid, EMBASE (1980 to May 2012) and Web of Science (1945 to May 2012); we screened the reference lists of all eligible trials and reviews to look for further trials and contacted authors of trials to ask for additional information. We searched for ongoing trials at http://www.controlledtrials.com/ and http://clinicaltrials.gov/ . We reran our search of all databases listed above on 21 November 2013. SELECTION CRITERIA: We included published and unpublished randomized controlled trials, regardless of blinding or language of publication, in participants 18 years of age or older who were scheduled for an elective AFOI because of an anticipated difficult airway. Participants received dexmedetomidine or control medications. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data on study design, participants, interventions and outcomes. We assessed risk of bias using The Cochrane Collaboration's tool. We estimated risk ratios (RRs) or mean differences (MDs) with 95% confidence internals (CIs) for outcomes with sufficient data; for other outcomes, we performed a qualitative analysis. MAIN RESULTS: We identified four randomized controlled trials (RCTs), which included 211 participants. The four trials compared dexmedetomidine with midazolam, fentanyl, propofol or a sodium chloride placebo, respectively. The trials showed low or unclear risk of bias primarily because information provided on allocation concealment and other potential sources of bias was inadequate. Owing to clinical heterogeneity and potential methodological heterogeneity, it was impossible to conduct a full meta-analysis. We described findings from individual studies or presented them in tabular form. Limited evidence was available for assessment of the outcomes of interest for this review. Results of the limited included trials showed that dexmedetomidine significantly reduced participants' discomfort with no significant differences in airway obstruction, low oxygen levels or treatment-emergent cardiovascular adverse events noted during AFOI compared with control groups. When the search was rerun (from May 2012 to November 2013), it was noted that four studies are awaiting assessment. We will deal with these studies when we update the review. AUTHORS' CONCLUSIONS: Small, limited trials provide weak evidence to support dexmedetomidine as an option for patients with an anticipated difficult airway who undergo AFOI. The findings of this review should be further corroborated by additional controlled investigations.

Rescue of cAMP response element-binding protein signaling reversed spatial memory retention impairments induced by subanesthetic dose of propofol.

AIMS: The intravenous anesthetic propofol caused episodic memory impairments in human. We hypothesized propofol caused episodic-like spatial memory retention but not acquisition impairments in rats and rescuing cAMP response element-binding protein (CREB) signaling using selective type IV phosphodiesterase (PDEIV) inhibitor rolipram reversed these effects. METHODS: Male Sprague-Dawley rats were randomized into four groups: control; propofol (25 mg/kg, intraperitoneal); rolipram; and rolipram + propofol (pretreatment of rolipram 25 min before propofol, 0.3 mg/kg, intraperitoneal). Sedation and motor coordination were evaluated 5, 15, and 25 min after propofol injection. Invisible Morris water maze (MWM) acquisition and probe test (memory retention) were performed 5 min and 24 h after propofol injection. Visible MWM training was simultaneously performed to resist nonspatial effects. Hippocampal CREB signaling was detected 5 min, 50 min, and 24 h after propofol administration. RESULTS: Rolipram did not change propofol-induced anesthetic/sedative states or impair motor skills. No difference was found on the latency to the platform during the visible MWM. Propofol impaired spatial memory retention but not acquisition. Rolipram reversed propofol-induced spatial memory impairments and suppression on cAMP levels, CaMKIIα and CREB phosphorylation, brain-derived neurotropic factor (BDNF) and Arc protein expression. CONCLUSIONS: Propofol caused spatial memory retention impairments but not acquisition inability possibly by inhibiting CREB signaling.

Dexmedetomidine versus morphine or fentanyl in the management of children after tonsillectomy and adenoidectomy: a meta-analysis of randomized controlled trials.

OBJECTIVES: The primary objective of this review was to evaluate and compare the efficacy and safety of dexmedetomidine hydrochloride with the efficacy and safety of opioids for postoperative management of children after tonsillectomy and adenoidectomy. METHODS: We searched the Cochrane Central Register of Controlled Trials (Central) in the Cochrane Library (most recent issue), Medline (1966 to date) through Ovid, Embase (1980 to date), and Web of Science (1945 to date). The number of patients who required rescue analgesics (morphine or fentanyl) in the postanesthesia care unit, the number of patients with emergence agitation, the number of patients with postoperative nausea and vomiting, the time to eye-opening in response to verbal stimuli, and the time to extubation were analyzed. RESULTS: We included 5 trials, consisting of 482 patients in total. There were no significant differences in the number of patients who required rescue analgesics in the postanesthesia care unit, the number of patients with emergence agitation, the number of patients with postoperative nausea and vomiting, or the time to extubation between patients who received dexmedetomidine and those who received opioids. Compared with opioids, dexmedetomidine was associated with a significantly decreased time to eye-opening in response to verbal stimuli (mean difference, -2.11 minutes; 95% confidence interval, -3.32 to -0.91 minutes; p = 0.0006). CONCLUSIONS: Intraoperative use of dexmedetomidine was as effective as opioids in preventing postoperative pain and emergence agitation in children who had undergone tonsillectomy and adenoidectomy.

MicroRNA-466l inhibits antiviral innate immune response by targeting interferon-alpha.

Effective recognition of viral infections and subsequent triggering of antiviral innate immune responses are essential for the host antiviral defense, which is tightly regulated by multiple regulators, including microRNAs (miRNAs). A previous study showed that miR-466l upregulates IL-10 expression in macrophages by antagonizing RNA-binding protein tristetraprolin-mediated IL-10 mRNA degradation. However, the ability of miR-466l to regulate antiviral immune responses remains unknown. Here, we found that interferon-alpha (IFN-α) expression was repressed in Sendai virus (SeV)- and vesicular stomatitis virus (VSV)-infected macrophages and in dendritic cells transfected with miR-466l expression. Moreover, multiple IFN-α species can be directly targeted by miR-466l through their 3' untranslated region (3'UTR). This study has demonstrated that miR-466l could directly target IFN-α expression to inhibit host antiviral innate immune response.

Autologous transplantation of peripheral blood-derived circulating endothelial progenitor cells attenuates endotoxin-induced acute lung injury in rabbits by direct endothelial repair and indirect immunomodulation.

BACKGROUND: Studies have demonstrated the role of circulating endothelial progenitor cells (EPCs) in maintaining normal endothelial function and in endothelial repairing. This study was aimed to observe the protective effects of autologous transplantation of circulating EPCs against endotoxin-induced acute lung injury in rabbits and to investigate the underlying mechanisms. METHODS: One-hundred-and-fifty rabbits were enrolled. After acute lung injury was induced by endotoxin, autologous circulating EPCs, endothelial cell, or normal saline were transfused intravenously, respectively. Pao(2)/FiO(2) ratios, concentrations of plasma nitric oxide, malonyldialdehyde, and activity of superoxide dismutase were examined. The lung wet-to-dry weight ratios were counted; polymorphonuclear cell ratios and areas of hyaline membrane formation and hemorrhage were measured. The levels of interleukin-1ß, E-selectin, intercellular adhesion molecule-1, interleukin-10, vascular endothelial growth factor protein, and inducible nitric oxide synthase protein were analyzed. RESULTS: Pao(2)/FiO(2) ratios were significantly increased with EPC transfusion. Infiltration of polymorphonuclear cells, lung wet-to-dry weight ratios, and area of hyaline membrane and hemorrhage in lung tissue were significantly decreased after EPC transplantation. Plasma level of nitric oxide and malondialdehyde were significantly inhibited, and the activity of superoxide dismutase was enhanced in the EPC-treated animals. EPC transplantation significantly increased level of interleukin-10 and vascular endothelial growth factor protein and reduced levels of interleukin-1ß, E-selectin, intercellular adhesion molecule-1, and inducible nitric oxide synthase in injury lung tissues. CONCLUSIONS: Autologous transplantation of circulating EPCs can partly restore the pulmonary endothelial function and effectively attenuate endotoxin-induced acute lung injury by direct endothelial repair and indirect immunomodulation of antioxidation and antiinflammation.

Hydroxyethyl starch for cardiovascular surgery: a systematic review of randomized controlled trials.

PURPOSE: The objective of this study was to appraise the safety profiles of HES preparations and to find out which HES preparation was the most acceptable in cardiovascular surgery through a comparison with control solutions. METHODS: Pertinent randomized controlled trials were selected through a search of Pubmed, Embase, and Cochrane Controlled Trials Register. Quantitative and qualitative analysis was carried out to evaluate blood loss, blood transfusion, renal function, complications, reoperation, and mortality. RESULTS: A total of 3,234 patients from 52 randomized controlled trials were included. HES preparations versus control solutions in blood loss: HES 130 kD vs. albumin (SMD -0.61, 95% CI -0.82, -0.40), HES 200 kD vs. albumin (SMD -0.01, 95% CI -0.29, 0.28), HES 450 kD vs. albumin (SMD 0.47, 95% CI 0.26, 0.68). When comparing control solutions with HES preparations, 50% (HES 450 kD), 40.9% (HES 200 kD), and 18.2% (HES 130 kD) of the comparisons showed more blood/blood products infusion with HES than with control solutions. A numerically lower mortality rate seemed to be related to HES preparations (2.68 vs 4.23%). No difference was found in terms of complications, renal failure, or reoperation. CONCLUSIONS: Perioperative administration of HES preparations is comparatively safe. The data appraising safety profiles of HES preparations are insufficient to make direct comparisons among themselves. As the third generation of HES preparations, HES 130 kD showed a trend toward lower blood loss and transfusion rates and is a suitable choice for cardiovascular surgery.

Role of mast cell activation in inducing microglial cells to release neurotrophin.

The brain-derived neurotrophic factor (BDNF) plays a critical role in pain hypersensitivity. BDNF is the ligand of P2X4 receptors (P2X4R) in the microglia. The causative factors involving the P2X4R over expression in the microglia remains unclear. Mast cell activation has a close relation with pain hypersensitivity. However, the underlying mechanism between mast cell activation and pain hypersensitivity is unknown. The present study aimed to elucidate the mechanism by which mast cell activation promoted the expression of P2X4R in the microglia. The results of present study showed that mast cell activation markedly promoted the expression of P2X4R and BDNF in microglial cells, which significantly enhanced the release of BDNF from microglial cells upon exposure to adenosine triphosphate. Mast cell-derived tryptase activated PAR2 that resulted in promoting the expression of P2X4R in microglial cells. Pretreatment with antibodies against tryptase or PAR2, or using tryptase-deficient HMC-1 cells or PAR2-deficient microglial cells abolished the increase in P2X4R expression and BDNF release. Increase in mitogen activated protein kinase phosphorylation was observed in the processes of mast cell-induced BDNF release and P2X4R expression. We conclude that mast cell activation has the capacity to promote the expression of P2X4R and BDNF in microglial cells.

[Changes in alpha2-adrenergic receptors gene expression after high-level spinal cord injury in Wistar rats].

OBJECTIVE: To evaluate the change in alpha(2)-adrenergic receptors (alpha(2)-ARs) gene expression after high-level injury of the spinal cord (SCI), aiming as developing a more effective perioperative anesthetic management for high-level SCI patients. METHODS: Adult male Wistar rats were anesthetized and severe spinal crush injury at T4 was produced using modified Allens device. The expression of alpha(2)-ARs mRNA at different levels of spinal cord in normal control rats (C), injured segment (I), above (A) and below (B) the site of injured segment, were measured by reverse transcription-polymerase chain reaction (RT-PCR) 1 day, 3 days, 1 week, 2 weeks, 3 weeks and 4 weeks, respectively after SCI. RESULTS: Compared with group C (sham group), in group A the expression of alpha(2)-ARs mRNA decreased 1 day after SCI (P<0.05) and dropped to the nadir 2 weeks later (P<0.01), but the expression was restored to the normal level 4 weeks later. In group I the lowering of alpha(2)-ARs mRNA expression occurred immediately after SCI and down to the lowest value 1 week later (P<0.01), and did not recover to normal level 4 weeks later (P<0.05). In group B downregulation of alpha(2)-ARs mRNA expression was detected 1 day after SCI (P<0.05), but it was upregulated 1 week later reaching the normal level, which was maintained for 4 weeks. CONCLUSION: In a chronic SCI rat model, alpha(2)-ARs gene expression is downregulated in the injured segment, but returns to the normal level above and below the injured segment. The changes in alpha(2)-ARs may be a pivotal factor contributing to a series of abnormal responses after high-level SCI.

[Effect of high level spinal cord injury on rat heart function].

OBJECTIVE: To study the effects of high level spinal cord injury (SCI) on rat heart, and investigate the role of endothelin-1 (ET-1) in the harmful effects on heart after SCI. METHODS: Forty-eight male SD rats were randomly divided into six groups of 8 animals each: control group; 4-hour group: 4 th hour after injury to spinal cord at cervical 7 level; 12-hour group: 12 th hour after injury to 7 spinal cord at C7 level; 24-hour group with same injury; 48-hour group and 72-hour group, all with same injury. Mean arterial pressure (MAP), heart rate (HR), left ventricle systolic pressure (LVSP), and left ventricular maximum velocities of contraction (+/-dp/dt max) were recorded in each group. Lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB) and ET-1 contents in the myocardium. were also measured. Specimens of the myocardium were harvested for ultrastructure examination with transmission electron microscopy. RESULTS: Hemodynamics variables including HR, MAP, LVSP and+/-dp/dtmax were significantly decreased in all the injury groups compared with that of control group (P<0.05 or P<0.01). These variables in 12-hour group showed lowest values among all the groups (all P<0.01). But the values of cardiac enzymes were much higher in five injury groups compared with that of control group (P<0.05 or P<0.01). ET-1 contents in serum and cardiac tissue raised markedly after the injury was inflicted to the animals (P<0.05), reaching peak at 12 hours (P<0.01). Ultrastructural examination of the myocardial tissue demonstrated that there were mild dissolution of myocardial fibrils and vacuolation of mitochondria at 12 hours after injury. CONCLUSION: High level SCI could induce myocardial injuries and an excessive production of ET-1 in circulation and myocardial tissue might play a role in myocardial damage after injury of the spinal cord at a high level.