ABSTRACT
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis mediated by anti-NMDAR antibody. Current studies have found that most patients with anti-NMDAR encephalitis have a good prognosis after immunotherapy and tumor therapy, but there are still 4.5%-36.4% patients with relapse. It is important to identify the risk factors for the prevention of relapse. This article aims to review the relapse risk factors of NMDAR encephalitis in order to provide help for the prevention of relapse.
ABSTRACT
Objective:To evaluate the role of N-methyl-D-aspartate receptors (NMDA receptors) in sevoflurane anesthesia-caused necroptosis in hippocampal neurons of aged mice.Methods:Ninety clean-grade healthy male C57BL/6 mice, aged 18 months, weighing 27-30 g, were divided into 3 groups ( n=30 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S) and sevoflurane anesthesia plus NMDA receptor antagonist memantine hydrochloride group (group S+ M). Mice inhaled 3% sevoflurane for 2 h for 3 consecutive days in S group and S+ M group, and memantine hydrochloride 20 mg/kg was intraperitoneally injected at 1 h before each inhalation of sevoflurane in S+ M group.Mice only inhaled pure oxygen for 2 h in group C. Ten mice of each group were selected on 1 day before anesthesia and 3 and 7 days after anesthesia to perform Morris water maze test.The mice were sacrificed immediately after Morris water maze test, and hippocampus was removed for microscopic examination of pathological changes (with a light microscope) and for determination of the necroptosis rate of neurons and cytoplasmic free calcium concentration([Ca 2+ ] i)(by flow cytometry), and expression of NMDA receptor subtypes GluN2A, GluN2B and receptor-interacting protein kinase 1 (RIP1) (by Western blot). Results:Compared with group C, the escape latency was significantly prolonged, and the frequency of crossing the original platform was decreased, and the [Ca 2+ ] i and neuronal necroptosis rate in the hippocampus were increased at each time point after anesthesia, and the expression of GluN2A, GluN2B and RIP1 was up-regulated( P<0.05), and the pathologic changes were accentuated in S group and S+ M group.Compared with group S, the escape latency was significantly shortened, and the frequency of crossing the original platform was increased, and the [Ca 2+ ] i and neuronal necroptosis rate in the hippocampus were decreased at each time point after anesthesia, and the expression of GluN2A, GluN2B and RIP1 was down-regulated ( P<0.05), and the pathologic changes were attenuated in group S+ M. Conclusions:NMDA receptors are involved in the process of cognitive dysfunction induced by sevoflurane anesthesia in aged mice, and the mechanism may be related to the promotion of necrptosis in hippocampal neurons.
ABSTRACT
Herpes simplex virus encephalitis (HSE) is a common form of viral encephalitis, often with a single-phase course. A case of HSE with abnormal mental behavior as the main manifestation, admitted in Peking University Shenzhen Hospital in Octorber 2020, which improved after sufficient antiviral treatment was reported. After 2 months, abnormal mental behavior with memory deterioration recurred. It was considered as anti-N-methyl-D-aspartate receptor antibody combined with anti-glutamic decarboxylase antibody double-positive encephalitis, and improved after rituximab treatment. At present, there is no clinical report of such double antibody positive autoimmune encephalitis secondary to HSE. The purpose of this case report is to raise clinician awareness of post-HSE autoimmune encephalitis.
ABSTRACT
Objective:To explore the clinical characteristics, therapeutic effect and prognosis of movement disorders in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.Methods:The prospectively collected data of hospitalized 163 patients with anti-NMDAR encephalitis admitted to Xuanwu Hospital, Capital Medical University from June 2012 to October 2019 were analyzed. According to the presence of movement disorders, the patients were divided into movement disorders group (75 cases, 46.0%) and non-movement disorders group (88 cases, 54.0%). Patients were followed up for six months and 12 months after immunotherapy. The clinical manifestations, auxiliary examinations, treatment and prognosis of the two groups were compared.Results:Among 163 patients with anti-NMDAR encephalitis, 91 patients (55.8%) were male and 72 patients (44.2%) were female, with an age of 26(19, 34) years. In the 75 patients of the movement disorders group, 50 patients (66.7%) presented with orofacial dyskinesia, 45 patients (60%) with limb stereotypies, 28 patients (37.3%) with choreoathetosis, nine patients (12.0%) with ballism, seven patients (9.3%) with bradykinesia, five patients (6.7%) with tremor, and 13 patients (17.3%) with status dystonicus. Compared with the non-movement disorders group, the movement disorders group had a higher proportion of ovarian teratoma (14.7% vs 3.4%), modified Rankin Scale score of 3-5 before immunotherapy (76.0% vs 33.0%), abnormal electroencephalogram (89.3% vs 77.3%), increased lumbar puncture pressure (53.3% vs 34.1%), cerebrospinal fluid (CSF) pleocytosis (73.3% vs 51.1%), strong positive NMDAR antibody of CSF (44.0% vs 25.0%), admitting to intensive care unit (60.0% vs 9.1%), treated with intravenous immunoglobulin (80.0% vs 40.9%), plasma exchange (36.0% vs 3.4%), and immunosuppressive therapy (37.2% vs 17.0%); had shorter days from the onset to the beginning of immunotherapy [20(10, 33) d vs 35(15, 77) d]; had longer days from the beginning of immunotherapy to the improvement [34(20, 60) d vs 20(15, 35) d]; and there were significant differences of above items between the two groups ( P<0.05). There was no significant difference in the prognosis and relaps between the two groups at six and 12 months after immunotherapy. Conclusions:Nearly a half of patients with anti-NMDAR encephalitis had movement disorders with multiple phenotypes. The severity of movement disorders was related to the severity of the disease. After active immunotherapy and symptomatic treatment, movement disorders improved with the improvement of primary disease in majority of patients.
ABSTRACT
Objective:To analyze the clinical characteristics of patients with double-positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody and anti-N-methyl-D-aspartate receptor (NMDAR) antibody, so as to raise awareness of such diseases and improve the prognosis.Methods:Eighteen patients (double positive group) with positive serum anti-MOG antibody and cerebrospinal fluid anti-NMDAR antibody in Huashan Hospital, Fudan University from March 2017 to March 2020 were retrospectively analyzed. Using the SPSS software for simple random sampling, anti-MOG group(20 cases) and anti-NMDAR group (20 cases) were randomly selected at the same time for comparison. The anti-MOG group referred to the patients only with positive serum anti-MOG antibody. While the anti-NMDAR group referred to the patients whose cerebrospinal fluid anti-NMDAR antibody was positive. The clinical characteristics, laboratory examination results, radiological characteristics and prognosis of the three groups were collected and analyzed.Results:There was no statistically significant difference in demographic data among the three groups ( P>0.05). The symptoms of patients in the double-positive group were divided into two categories by cluster analysis, which corresponded to the symptom groups obtained by cluster analysis of the anti-MOG group and the anti-NMDAR group, and the same result was verified by correspondence analysis. Compared with the anti-MOG group, the incidence of epilepsy (10/18 vs 3/20, P=0.016), psychosis and behavior change (8/18 vs 0/20, P=0.001), visual disturbances (8/18 vs 17/20, P=0.016), dysarthria/dysphagia (8/18 vs 1/20, P=0.007) was significantly different in the double-positive group ( P<0.017). Compared with the anti-NMDAR group, the incidence of ataxia (8/18 vs 19/20, P=0.001), psychosis and behavior change (12/18 vs 1/20, P<0.001) was significantly different in the double-positive group. There was no statistically significant difference in the combination rate of thyroid peroxidase antibody, thyroglobulin antibody and antinuclear antibody between two groups, and the cerebrospinal fluid pressure, white blood cell count, protein, glucose, chloride and positive rate of oligoclonal band were also not statistically different between two groups ( P>0.017; P<0.017 indicates statistically significant difference by Bonferroni corrected multiple comparisons). Compared with the anti-NMDAR group, whether the brain magnetic resonance imaging had lesions was different in double positive group (18/18 vs 8/20, P<0.001). The initial modified Rankin Scale (mRS) scores before treatment were different among the double positive group, anti-MOG group and anti-NMDAR group (3.72±0.96, 2.75±0.97, 3.95±0.76, respectively, F=10.004, P<0.001), but there was no statistically significant difference in the scores after six-month treatment (1.22±1.44, 0.40±0.75, 1.20±1.24, respectively, F=3.153, P=0.051), and the recurrence rate of the disease was different among the three groups (8/18, 14/20, 5/20, respectively, χ2=10.004, P=0.017). Conclusions:Anti-MOG antibodies and anti-NMDAR antibodies could exist at the same time, showing clinical phenotype overlap, which was a new syndrome called the overlapping syndrome of myelin oligodendrocyte glycoprotein antibody-associated disease and NMDAR encephalitis, MNOS. The condition of MNOS patients was more severe than that of patients with MOG antibody-associated disease (MOGAD), but patients with MNOS, MOGAD, and anti-NMDAR encephalitis all responded well to immunosuppressive therapy. It was suggested that early second-line immunotherapy should be given to reduce the recurrence rate in patients with MNOS and MOGAD.
ABSTRACT
Objective:To evaluate the role of spinal P2Y1R in the development of remifentanil-induced hyperalgesia in rats with incisional pain (IP) and the relationship with the function of NR1 and NR2B in spinal cord.Methods:Forty-eight healthy adult male Sprague-Dawley rats, aged 10-12 weeks, weighing 250-280 g, in which intrathecal catheters were successfully placed, were divided into 6 groups ( n=8 each) using a random number table method: control group (group C), P2Y1R antagonist MRS2179 group (group M), remifentanil group (group R), remifentanil plus MRS2179 group (group R+ M), IP plus remifentanil group (group I+ R) and IP plus remifentanil plus MRS2179 group (group I+ R+ M). In group C, normal saline 10 μl was intrathecally injected, and 10 min later normal saline was infused for 60 min via the tail vein at a rate of 0.1 ml·kg -1·min -1.In group M, MRS2179 0.6 nmol/kg was intrathecally injected, and 10 min later normal saline was infused for 60 min via the tail vein at a rate of 0.1 ml·kg -1·min -1.In group R, normal saline 10 μl was intrathecally injected, and 10 min later remifentanil was infused for 60 min via the tail vein at a rate of 1 μg·kg -1·min -1.In group R+ M, MRS2179 0.6 nmol/kg was intrathecally injected, and 10 min later remifentanil was infused for 60 min at a rate of 1 μg·kg -1·min -1 via the tail vein.In group I+ R, normal saline 10 μl was intrathecally injected, 10 min later remifentanil was infused for 60 min via the tail vein at a rate of 1 μg·kg -1·min -1, and IP was established at 10 min after onset of remifentanil infusion.In group I+ R+ M, MRS2179 0.6 nmol/kg was intrathecally injected, 10 min later remifentanil was infused via the tail vein for 60 min at a rate of 1 μg·kg -1·min -1, and IP was established at 10 min after onset of remifentanil infusion.The mechanical paw withdrawal threshold (MWT), thermal paw withdrawal latency (TWL), and the number of paw lifts on the cold plate were measured at 24 h before infusion of remifentanil or normal saline and at 2, 6, 24, and 48 h after the end of infusion.The animals were sacrificed after the last measurement of the pain threshold, L 4-6 segments of the spinal cord were removed for determination of the expression of P2Y1R, phosphorylated NR1 (p-NR1), NR1, phosphorylated NR2B (p-NR2B) and NR2B (by Western blot), for calculation of the ratios of p-NR1/NR1 and p-NR2B/NR2B, and for detection of expression of P2Y1R mRNA, NR1 mRNA and NR2B mRNA (by real-time polymerase chain reaction). Results:Compared with group C, MWT was significantly decreased, TWL was shortened, the number of paw lifts on the cold plate was increased, the expression of P2Y1R protein and mRNA, NR1 protein and mRNA, p-NR1, NR2B protein and mRNA and p-NR2B was up-regulated, and p-NR1/NR1 ratio and p-NR2B/NR2B ratio were increased in group R ( P<0.01). Compared with group R, MWT was significantly increased, TWL was prolonged, the number of paw lifts on the cold plate was decreased, the expression of P2Y1R, p-NR1, NR1 protein and mRNA, p-NR2B, NR2B protein and mRNA was down-regulated, and p-NR1/NR1 ratio and p-NR2B/NR2B ratio were decreased in group R+ M ( P<0.05 or 0.01). Compared with group I+ R, MWT was significantly increased, TWL was prolonged, the number of paw lifts on the cold plate was decreased, the expression of P2Y1R, p-NR1, NR1 protein and mRNA, p-NR2B, NR2B protein and mRNA was down-regulated, and p-NR1/NR1 ratio and p-NR2B/NR2B ratio were decreased in group I+ R+ M ( P<0.01). Conclusion:Spinal P2Y1R can enhance the function of NR1 and NR2B, which may be involved in the development of remifentanil-induced hyperalgesia in rats with IP.
ABSTRACT
Objective@#To evaluate the role of 2B-containing NMDA receptors (NR2B) in sevoflurane anesthesia-induced cognitive dysfunction in aged rats.@*Methods@#Thirty-two healthy male Sprague-Dawley rats, aged 18 months, weighing 570-630 g, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S), sevoflurane anesthesia plus NR2B specific inhibitor Ro 25-6981 group (group S+ RO) and Ro 25-6981 group (group RO). S and S+ RO groups inhaled 3% sevoflurane for 4 h. Ro 25-6981 1 mg/kg was intraperitoneally injected at 15 min before inhaling sevoflurane in group S+ RO.Morris water maze test was performed at 2 days after the end of anesthesia to assess cognitive function.The rats were then sacrificed, and hippocampal tissues were obtained for determination of the expression and phosphorylation of ERK1/2 by Western blot.@*Results@#Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was reduced, the time of staying at the original platform quadrant was shortened, and the phosphorylation of ERK1/2 was decreased in group S (P<0.05), and no significant change was found in the escape latency in S+ RO and RO groups (P>0.05). Compared with group S, the escape latency was significantly shortened, the frequency of crossing the original platform was increased, the time of staying at the original platform quadrant was prolonged, and the phosphorylation of ERK1/2 was increased in group S+ RO(P<0.05). There was no significant difference in ERK1/2 expression among the four groups (P>0.05).@*Conclusion@#The mechanism by which sevoflurane anesthesia induces cognitive dysfunction is related to up-regulating the expression of NR2B and inhibiting the activity of ERK1/2 in aged rats.
ABSTRACT
Objective To evaluate the role of 2B-containing NMDA receptors(NR2B)in sevoflu-rane anesthesia-induced cognitive dysfunction in aged rats.Methods Thirty-two healthy male Sprague-Dawley rats,aged 18 months,weighing 570-630 g,were divided into 4 groups(n＝8 each)using a ran-dom number table method: control group(group C),sevoflurane anesthesia group(group S),sevoflurane anesthesia plus NR2B specific inhibitor Ro 25-6981 group(group S+RO)and Ro 25-6981 group(group RO).S and S+RO groups inhaled 3％sevoflurane for 4 h.Ro 25-6981 1 mg/kg was intraperitoneally injec-ted at 15 min before inhaling sevoflurane in group S+RO.Morris water maze test was performed at 2 days af-ter the end of anesthesia to assess cognitive function.The rats were then sacrificed,and hippocampal tis-sues were obtained for determination of the expression and phosphorylation of ERK1/2 by Western blot.Results Compared with group C,the escape latency was significantly prolonged,the frequency of crossing the original platform was reduced,the time of staying at the original platform quadrant was shortened,and the phosphorylation of ERK1/2 was decreased in group S(P＜0.05),and no significant change was found in the escape latency in S+RO and RO groups(P>0.05).Compared with group S,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the time of staying at the original platform quadrant was prolonged,and the phosphorylation of ERK1/2 was increased in group S+RO(P＜0.05).There was no significant difference in ERK1/2 expression among the four groups(P>0.05).Conclusion The mechanism by which sevoflurane anesthesia induces cognitive dysfunction is re-lated to up-regulating the expression of NR2B and inhibiting the activity of ERK1/2 in aged rats.
ABSTRACT
Objective@#To investigate the clinical features, treatment strategies and long term outcomes of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.@*Methods@#The data of clinical features, auxiliary examinations, treatments and prognosis in children with anti-NMDAR encephalitis in Xiangya Hospital of Central South University from March 2014 to October 2017 were collected and retrospectively analyzed. A total of 71 patients were enrolled, including 33 males and 38 females. The youngest age of onset was 4 months old, and the age of onset was (9±4) years. The first-line immunotherapy treatment for anti-NMDAR encephalitis was short course corticosteroid (high-dose impulse therapy and oral maintenance therapy for 1 month in acute period) and (or) immunoglobulin. The clinical evaluation was performed 2 weeks after first-line immunotherapy treatment. The second-line immunotherapy treatment, including rituximab and (or) cyclophosphamide, would be started if the symptoms did not improve significantly and the modified Rankin scale (mRS) score ≥3. All patients were followed up and evaluated for prognosis. T-test, Mann-Whitney U, Chi square test and Fisher′s exact probability method were used for comparison between good outcome group and poor outcome group, first-line immunotherapy group and first-line immunotherapy combined with second-line immunotherapy group.@*Results@#The more common clinical manifestations were psychiatric symptoms (n=61, 86%), dyskinesia (n=55, 77%) and convulsions (n=51, 72%). Two cases (3%) had tumors. Electroencephalogram (EEG), cerebro-spinal fluid (CSF) and brain magnetic resonance imaging (MRI) studies were abnormal in 83% (59/71), 39% (27/69) and 38% (27/71) patients, respectively. For the treatment regimens, all the 71 patients underwent first-line immunotherapy, resulting in improvement within 14 days in 40 cases (56%), and 1 case (1%) died. The rest 30 cases (42%) received second-line immunotherapy. The patients were followed up for 5.0-41.8 months, with a median of 19.3 months. At the last follow-up, 49 cases (69%) recovered completely, 15 cases (21%) had mild disability, 6 cases (8%) had severe disability, 1 case (1%) died and 3 cases (4%) had relapse. There were significant differences between the groups with good prognosis and poor prognosis on admission to pediatric intensive care unit (PICU) and consciousness disorder (10/64 vs. 5/7, 39/64 vs. 7/7, P=0.047, 0.004). There were significant differences between first-line immunotherapy group and the first-line combined second-line immunotherapy group on admission to PICU, consciousness disorder, sleep disorder and first mRS score (12% (5/41) vs. 33% (10/30), 44% (18/41) vs. 93% (28/30), 56% (23/41) vs. 90% (27/30), 3 (1-5) vs. 4 (3-5), respectively; χ2=4.645, 18.555, 9.560, Z=5.184, P=0.031, <0.01, 0.002, <0.01, respectively).@*Conclusions@#Anti-NMDAR encephalitis can occur in all ages of children. The most common clinical manifestations are psychotic symptoms, dyskinesia and convulsions. Paraneoplastic cases are less common in children. Immunotherapy is effective. The second-line immunotherapy should be given after the failure of first-line therapy (mRS score≥3).
ABSTRACT
Antibody-related central nervous system (CNS) autoimmune diseases are a frontier of neuroimmunology.CNS viral infections including herpes simplex encephalitis and Japanese encephalitis can induce anti-N-methyl-D-aspartic acid receptor encephalitis with a double-peak presentation.Pathogenic antibody is the specific diagnostic biomarker which renders the establishment of new autoimmune entities.However,the pathogenicity and clinical relevance of some new antibodies need further evaluation.The challenge from cases with overlapping antibodies or antibody-negative limbic encephalitis can be solved with the reference to the diagnostic criteria and recommendation.
ABSTRACT
Anti-N-methyl-D-aspartate receptor (NMDAR) antibody is an autoimmune encephalitis antibody associated with Anti-NMDAR encephalitis.Since the discovery of the antibody in 2007,the basic research and clinical application of the antibody in the field of neuroimmunology have gradually increased.This article reviews the progress of anti-NMDAR antibody overview,the relationship between anti-NMDAR antibody and encephalitis,and the laboratory detection of anti-NMDAR antibody,so as to provide a reference for clinical diagnosis and treatment.
ABSTRACT
Epilepsy,a group of chronic neurological disorders characterized by spontaneous and recurrent seizures and learning and memory impairments,results in transient brain dysfunction due to sudden abnormal discharge of brain neurons.The pathogenesis of epilepsy is very complicated and has not yet been fully elucidated.The imbalance between excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) neurotransmitters in the central nervous system and changes in ionic functions of N-methyl-D-aspartate receptors directly induce epileptic seizures.The endocannabinoid system plays an important role in retrograde synaptic transmission and exerts the anti-epileptic effect in cannabinoid receptor 1 (CBR1) dependent manner by regulating the synaptic transmission of glutamatergic and GABAergic neurons and homeostatsis of ionic channel function.Elucidating the specific mechanism of action of CBR1 signaling pathway in epilepsy,can provide an effective theoretical basis and novel drug's target for clinical treatment of epilepsy.
ABSTRACT
Objective To evaluate the effect of dexmedetomidine on the expression of NR1 subunit-containing NMDA receptors and GIuR2 subunit-containing AMPA receptors during hypoxic injury to rat hippocampal neurons.Methods The hippocampal neurons were isolated from Wistar rats within 24 h after birth and divided into 3 groups (n=24 each) using a random number table:control group (group C),hypoxia group (group H) and dexmedetomidine group (group D).The cells were subjected to hypoxia for 6 h to establish the model of neuronal hypoxic injury in H and D groups.In group D,0.1 μmol/L dexmedetomidine was added at 6 h of hypoxia and neurons were incubated for 3 h,and then the culture medium was replaced with a normal medium and neurons were incubated for 24 h.The neuronal viability was measured by CCK-8 assay,the leakage of LDH was detected,and the leakage rate was calculated.The expression of NR1 subunits-containing NMDA receptors and GluR2 subunits-containing AMPA receptors was detected by Western blot.The concentration of calcium ion in cytoplasm was measured using Fluo-3AM.Results Compared with group C,the neuronal viability was significantly decreased,the LDH leakage rate was increased,the expression of NR1 subunits-containing NMDA receptors in the membrane was up-regulated,the expression of GluR2 subunits-containing AMPA receptors was down-regulated,and the concentration of calcium ion in cytoplasm was increased in H and D groups (P＜0.05).Compared with group H,the neuronal viability was significantly increased,the LDH leakage rate was decreased,the expression of NR1 subunits-containing NMDA receptors in the membrane was down-regulated,the expression of GluR2 subunitscontaining AMPA receptors was up-regulated,and the concentration of calcium ion in cytoplasm was decreased in group D (P＜0.05).Conclusion The mechanism by which dexmedetomidine reduces hypoxic injury to rat hippocampal neurons may be related to inhibiting up-regulation of the expression of NR1 subunits-containing NMDA receptors in the membrane and down-regulation of the expression of GluR2 subunitscontaining AMPA receptors.
ABSTRACT
Objective To investigate the effect of rhynchophylline on mRNA expression of excitatory amino acid transporter 2 (EAAT2 ) and N-methyl-D-aspartic acid receptor 2B (NR2B) after astrocyte oxygen-glucose deprivation. Methods The subcultured third generation astrocytes from the hippocampus were inoculated into 6-well plates, and they were divided into blank control group, hypoxia-ischemia group,low-dose rhynchophylline group (0. 02 mg/ml) and high-dose rhynchophylline group (0. 2 mg/ml) after the cells were attached to the wall and grew out protrusion. The total RNAs in each group were extracted.Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of EAAT2 and NR2B mRNA in astrocytes of each group. Results Compared with the blank control group, the expression levels of NR2B and EAAT2 mRNA in astrocytes of the ischemia-hypoxia group were significantly higher (all P < 0. 05 ). The expression levels of NR2B and EAAT2 mRNA in the low-dose rhynchophylline group were lower than those in ischemia-hypoxia group, but there was no significant difference. The expression levels of NR2B and EAAT2 mRNA in the high-dose rhynchophylline group were significantly lower than the ischemia-hypoxia group and the low-dose rhynchophylline group (all P < 0. 05).Conclusion The expression of EAAT2 and NR2B mRNA in astrocytes of hippocampus cultured in vitro was significantly increased after ischemia and hypoxia, and rhynchophylline intervention could significantly reduce its expression in a concentration dependent manner.
ABSTRACT
Objective To evaluate the effect of dexmedetomidine on Src-mediated NR2A tyrosine phosphorylation in hippocampal neurons subjected to hypoxia-reoxygenation (H/R) in mice.Methods C57 mice at 18 days of gestation were sacrificed by pulling neck,fetal mice were obtained by caesarean section,and hippocampal neurons were isolated.Neurons were cultured in culture medium for 7 days and then divided into 3 groups (n =30 each) using a random number table method:control group (group C),H/R group and dexmedetomidine group (D group).Hippocampal neurons were exposed to 95％ N2-5％ CO2 in an incubator at 37 ℃ for 4 h followed by reoxygenation with 95％ O2-5％ CO2 for 24 h to establish the model of H/R.Dexmedetomidine was given at a final concentration of 1 μ mol/L,and neurons were incubated for 4 h before establishing the model.The viability of hippocampal neurons was measured by MTT assay,TUNEL staining was used to observe apoptosis in hippocampal neurons,and the expression of c-Src,phosphorylated Src Y416 (p-Src Y416),NR2A,phosphorylated NR2A Y1325 (p-NR2A Y1325) and cleaved caspase-3.was determined by Western blot.Apoptosis index was calculated.Results Compared with group C,the viability of hippocampal neurons was significantly decreased,apoptosis index was increased,and the expression of p-Src Y416,p-NR2A Y1325 and cleaved caspase-3 was up-regulated in group H/R (P＜0.05).Compared with group H/R,the viability of hippocampal neurons was significantly increased,apoptosis index was decreased,and the expression of p-Src Y416,p-NR2A Y1325 and cleaved caspase-3 was down-regulated in group D (P＜0.05).There was no significant difference in the expression of c-Src and NR2A among three groups (P＞0.05).Conclusion Dexmedetomidine can inhibit apoptosis in hippocampal neurons subjected to H/R,and the mechanism may be associated with decreasing Src-mediated NR2A tyrosine phosphorylation in mice.
ABSTRACT
Objective To evaluate the effect of propofol on subunit 2B-containing N-methyl-D-aspartate receptor (NR2B)/calcium/calmodulin-dependent protein kinase Ⅱ alpha (CaMKⅡα) signaling pathway in brain injury induced by hepatic ischemia-reperfusion (I/R) in preadolescent mice.Methods Sixty-four healthy clean-grade C57BL/6 mice,aged 2 weeks,weighing 4-6 g,were randomized into 4 groups (n=16 each) using a random number table method:sham operation group (S group),hepatic I/R group (HI/R group),propofol control group (P group),and propofol plus hepatic I/R group (P+ HI/R group).The model of 70％ liver I/R injury was established by clamping the left and middle lobe vascular trunk in anesthetized mice.Propofol 20 mg/kg was intraperitoneally injected before operation at 30 min before establishing the model in P and P+HI/R groups.The equal volume of normal saline was given instead in P and P + HI/R groups.Eight mice of each group were sacrificed at 6h of reperfusion,hippocampal tissues were obtained for examination of pathological changes of hippocampal tissues and for determination of neuronal apoptosis (by TUNEL) and expression of NR2B,phosphorylated NR2B (p-NR2B),CaMKⅡα and phosphorylated CaMKⅡα (p-CaMKⅡα) (by Western blot).The remaining 8 mice in each group were used for Morris water maze test at 1 month after establishing the model.Apoptosis index was calculated.Results Compared with group S,the escape latency was significantly prolonged,the percentage of the time of staying at the original platform quadrant was decreased,the expression of p-NR2B and p-CaMKⅡα was up-regulated,and apoptosis index was increased in HI/R and P+HI/R groups (P＜0.05),and no significant change was found in the parameters mentioned above in group P (P＞0.05).Compared with group HI/R,the escape latency was significantly shortened,the percentage of the time of staying at the original platform quadrant was increased,the expression of p-NR2B and p-CaMKⅡα was down-regulated,and apoptosis index was decreased (P＜0.05),and the pathological changes of hippocampal tissues were significantly attenuated in group P+HI/R.Conclusion The mechanism by which propofol reduces brain injury induced by hepatic I/R may be related to inhibiting NR2B/CaMKⅡα signaling pathway in preadolescent mice.
ABSTRACT
Objective To evaluate the effect of propofol on the expression of programmed death-ligand-1 (PD-L1) in pancreatic cancer cells and the relationship with NMDA/Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ)/hypoxia-inducible factor-1α (HIF-1α) pathway.Methods Human pancreatic cancer cells were divided into 5 groups (n=16 each) by a simple random sampling method:control group (group C),propofol group (group P),KN93 (CaMK Ⅱ inhibitor) group,MK801 (NMDA receptor antagonist) group and propofol plus rapastinel (NMDA receptor agonist) group (group PR).Cells were cultured in DMEM supplemented with 10％ fetal bovine serum in group C.Cells were incubated for 8 h with 50 μmol/L propofol in group P.Cells were incubated for 8 h with 10 μmol/L KN93 in group KN93.Cells were incubated for 8 h with 500 μmol/L MK801 in group MK801.Cells were incubated for 8 h with 50 μmol/L propofol and 20 μmol/L rapastinel in group PR.After the end of treatment in each group,the cell viability was measured using CCK8 assay,the expression of PD-L1,HIF-1α,CaMK Ⅱ and phosphorylated CaMK Ⅱ (p-CaMK Ⅱ) was detected by Western blot,and intracellular calcium concentrations were determined by Fluo3/AM probe.Results Compared with group C,the cell viability was significantly decreased,the expression of PD-L1,HIF-1α and p-CaMK Ⅱ was down-regulated,and intracellular calcium concentrations were decreased in P,KN93 and MK801 groups (P＜0.05),and no significant change was found in group PR (P＞0.05).Compared with group P,the cell viability was significantly enhanced,the expression of PD-L1,HIF-1α and p-CaMK Ⅱ was up-regulated,and intracellular calcium concentrations were increased in group PR (P＜0.05).Conclusion The mechanism by which propofol inhibits the malignant potential of pancreatic cancer cells may be related to inhibiting NMDA/CaMK Ⅱ/HIF-1α pathway and down-regulating PD-L1 expression.
ABSTRACT
Objective To evaluate the effect of dexmedetomidine on remifentanil-induced miniature excitatory postsynaptic currents (mEPSCs) mediated by N-methyl-D-aspartate (NMDA) receptors in spinal dorsal horn neurons of rats.Methods Thirty male Sprague-Dawley rats,aged 14-18 days,weighing 50-60 g,were used in the study.Their lumbar segments of the spinal cord were immediately removed and sliced.A total of 180 slices were selected and divided into 5 groups (n=36 each) using a random number table:blank control group (group C),remifentanil group (group R),low-dose dexmedetomidine group (group L),moderate-dose dexmedetomidine group (group M) and high-dose dexmedetomidine group (group H).Spinal cord slices were incubated in artificial cerebrospinal fluid (ACSF) for 90 min in group C.Spinal cord slices were incubated for 90 min in ACSF with remifentanil at the final concentration of 4 nmol/L in group R.Spinal cord slices were incubated for 90 min in ACSF with remifentanil at the final concentration of 4 nmol/L and dexmedetomidine at the final concentrations of 2,4 and 6 nmol/L in L,M and H groups,respectively.The whole-cell patch-clamp technique was used to record the amplitude and time interval of NMDA receptors-mediated mEPSCs.Results Compared with group C,the amplitude of mEPSCs was significantly increased,and the time interval of mEPSCs was shortened in the other 4 groups (P＜ 0.05).Compared with group R,the amplitude of mEPSCs was significantly decreased,and the time interval of mEPSCs was prolonged in L,M and H groups (P＜0.05).Compared with group L,the amplitude of mEPSCs was significantly decreased,and the time interval of mEPSCs was prolonged in M and H groups (P＜0.05).Compared with group M,the amplitude of mEPSCs was significantly decreased,and the time interval of mEPSCs was prolonged in group H (P ＜ 0.05).Conclusion Dexmedetomidine weakens remifentanil-induced enhancement in the function of NMDA receptors in spinal dorsal horn neurons probably via the presynaptic and postsynaptie mechanisms in rats.
ABSTRACT
Objective To evaluate the effect of dexmedetomidine on remifentanil-induced miniature excitatory postsynaptic currents (mEPSCs) of N-methyl-D-aspartate (NMDA) receptors in spinal dorsal horn neurons of rats.Methods Thirty male Sprague-Dawley rats,aged 14-18 days,weighing 50-60 g,were used in the study.Their lumbar segments of the spinal cord were immediately removed and sliced.The 180 slices were divided into 5 groups (n =36 each) using a random number table:blank control group (group C),remifentanil group (group R),low-dose dexmedetomidine group (group L),moderate-dose dexmedetomidine group (group M) and high-dose dexmedetomidine group (group H).Spinal cord slices were incubated in artificial cerebrospinal fluid (ACSF) for 90 min in group C.Spinal cord slices were incubated for 90 min in ACSF with remifentanil at the final concentration of 4 nmol/L in group R.Spinal cord slices were incubated for 90 min in ACSF with remifentanil at the final concentration of 4 nmol/L and dexmedetomidine at the final concentrations of 2,4 and 6 nmol/L in L,M and H groups,respectively.The whole-cell patch-clamp technique was used to record the amplitude and time interval of mEPSCs of NMDA receptors.Results Compared with group C,the amplitude of mEPSCs was significantly increased,and the time interval of mEPSCs was shortened in the other 4 groups (P＜0.05).Compared with group R,the amplitude of mEPSCs was significantly decreased,and the time interval of mEPSCs was prolonged in L,M and H groups (P＜0.05).Compared with group L,the amplitude of mEPSCs was significantly decreased,and the time interval of mEPSCs was prolonged in M and H groups (P＜0.05).Compared with group M,the amplitude of mEPSCs was significantly decreased,and the time interval of mEPSCs was prolonged in group H (P＜0.05).Conclusion Dexmedetomidine weakens remifentanil-induced enhancement in the function of NMDA receptors in spinal dorsal horn neurons probably via the presynaptic and postsynaptic mechanisms in rats.
ABSTRACT
Objective To investigate the frequency of autoimmune encephalitis (AE) in limbic encephalitis (LE) syndrome and compare its clinical features with viral encephalitis.Methods Patients diagnosed with LE syndrome who admitted to Huashan Hospital between December 2015 and June 2016 were enrolled and screened for autoantibodies associated with AE (anti-N-methyl-D-aspartate receptor, anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, anti-gamma-amino-butyric acid B-receptor, anti-leucine-rich glioma inactivated 1 and anti-contactin-associated protein-like 2 antibodies) in cerebrospinal fluid (CSF) and serum. Their clinical features and auxiliary examinations were also collected and analyzed retrospectively. Results Fifty-four patients were diagnosed with LE syndrome, including 35 males and 19 females. The age of these patients was (38.98±17.29) (15-75) years. Twenty patients (37.0%) were identified as AE, 17 patients (31.5%) as viral encephalitis. Other cases included three (5.5%) with neurosyphilis, one (1.9%) with glioma and 13 (24.1%) of unknown cause. Young patients(15-29 years old)and patients older than 45 years accounted for 46.0% (17/37) and 37.8% (14/37) of all AE and viral encephalitis cases respectively. Patients with AE had longer disease progression time than patients with viral encephalitis ((22.45±11.62) d vs (6.24±2.95) d, t=6.015, P<0.01).Emergency hospitalization of patients with AE was less frequent than that of patients with viral encephalitis (3/20 vs 12/17, P=0.001). Patients with AE were less common to present with fever at disease onset than patients with viral encephalitis (8/20 vs 15/17, P=0.006). Seizures as the first neurological symptom were less common in AE than in viral encephalitis (2/20 vs 8/17, P=0.023). White blood cell counts in CSF were less frequently elevated in AE than in viral encephalitis (7/17 vs 12/15, P=0.036). The differences of age, gender, disease severity as well as abnormal rates of brain MRI, electroencephalogram and CSF protein were not statistically significant between the two groups. Tumors were discovered in 6 (6/19) patients with AE. Conclusions The frequency of AE in LE syndrome is not low. It is worthwhile to screen for autoantibodies associated with AE in patients diagnosed with LE syndrome. AE and viral encephalitis have their own characteristics, which could offer help in differential diagnosis between them and application of effective treatment.