ObjectiveTo evaluate the role of N-methyl-D-aspartate (NMDA) receptor in central nervous system (CNS) injury of obstructive jaundice. MethodThe related literatures about NMDA receptor and the CNS injury caused by hyperbilirubinemia were retrieved and reviewed. ResultsThe CNS injury of obstructive jaundice was related to overactivation of NMDA receptor, which finally resulted in degeneration and necrosis of nerve cells. The NMDA receptor antagonist MK-801 could relieve the CNS injury of obstructive jaundice. ConclusionsNMDA receptor plays an important role in the CNS injury caused by hyperbilirubinemia, and the blocker of NMDA receptor has protective effects in this process. However, there is no report of MK-801 in clinical application when hyperbilirubinemia happened.
ObjectiveTo analyze the diagnosis status and epidemiological characteristics of anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis) in the Sichuan province of China. MethodsIn the retrospective survey study, data of cases suspected as autoimmune encephalitis in Sichuan province from January 2012 to February 2017 were collected from the third-party test center.The diagnosis status and epidemiological characteristics of anti-NMDAR encephalitis were analyzed. Results① A total of 1 714 cases had been suspected as autoimmune encephalitis with anti NMDA receptor antibodies tested.In hospitals of capital city, cerebrospinal fluid or serum of 1 511 cases were tested since 2012.In other cities, 203 cases were tested since 2014.Hospitals with anti NMDA receptor antibodies tested increased by year.The cases distributed in the department of neurology, psychology, pychiatric, ICU, pediatrics, geriatrics, otolaryngology, infection, the mergency department and pneumology.② Cases with anti NMDA receptor antibodies tested increased by year.A total of 155 cases were confirmed as anti-NMDAR encephalitis, with the average onset age of (27.9±12.0) years ranged from 9 years to 77 years, including 89 women and 66 male.The female average age were (26.5±11.31) years, while the male were(29.0±13.0) years.③ Among the 155 confirmed cases, 127 cases with detailed clinical data were analyzed further.Seizure and behavior disorder were the main symptoms at onset.Among the 127 cases, 107 cases were misdiagnosed at their first hospital visit, with the misdiagnose rate of 84.3%.18 cases were reported with tumors (17 female), mainly with teratoma(11/17). ConclusionIn Sichuan province, the doctors of hospitals in non-capital city should strengthen the identification of autoimmune encephalitis.Anti-NMDAR encephalitis could be misdiagnosed easily and non-neurological physicians should also take attention;
ObjectiveTo analyze the protective mechanism of spinal cord ischemia-reperfusion injury mediated by N-methyl-D-aspartate (NMDA) receptor.MethodsA total of 42 SD rats were randomly assigned to 4 groups: a non-blocking group (n=6), a saline group (n=12), a NMDA receptor blocker K-1024 (25 mg/kg) group (n=12) and a voltage-gated Ca2+ channel blocker nimodipine (0.5 mg/kg) group (n=12). The medications were injected intraperitoneally 30 min before ischemia. The neural function was evaluated. The neuronal histologic change of spinal cord lumbar region, the release of neurotransmitter amino acids and expression of spinal cord neuronal nitric oxide synthase (nNOS) were compared.ResultsAt 8 h after reperfusion, the behavioral score of the K-1024 group was 2.00±0.00 points, which was statistically different from those of the saline group (5.83±0.41 points) and the nimodipine group (5.00±1.00 points, P<0.05). Compared with the saline group and nimodipine group, K-1024 group had more normal motor neurons (P<0.05). There was no significant difference in glutamic acid concentration in each group at 10 min after ischemia (P=0.731). The nNOS protein expression in the K-1024 group was significantly down-regulated compared with the saline group (P<0.01). After 8 h of reperfusion, the expression of nNOS protein in the K-1024 group was significantly up-regulated compared with the saline group (P<0.05).ConclusionK-1024 plays a protective role in spinal cord ischemia by inhibiting NMDA receptor and down-regulating nNOS protein expression; during the reperfusion, K-1024 has a satisfactory protective effect on spinal cord function, structure and biological activity of nerve cells.
Objective To study the differential expression profiling of the transcripts modified by m5C methylation in a rat model of N-methyl-D-aspartate (NMDA)-induced retinal excitotoxicity. MethodsA total of 65 Sprague Dawley male rats aged 7-8 weeks were randomly divided into two groups: normal control group and NMDA group. The right eye (model eye) of rats in the NMDA group were injected with 50.0 mmol/L of NMDA 3 μl in the vitreous cavity, while in the normal control group, equal volume of normal saline was injected into the vitreous cavity. After 1 week of the injection, the optic nerve conduction function of rats was detected by visual evoked potential. The whole structure of rat retina was observed by hematoxylin-eosin staining, and the thickness of each retinal layer and the number of retinal ganglion cell layer were detected. The number of β3 tubulin immunofluorescence positive cells was detected by immunofluorescence staining on retinal stretched preparation. Total RNA was extracted from the retinas of normal control group and NMDA group, and high-throughput m5C modified RNA was sequenced, and bioinformatics analysis was performed. The relative expression levels of SLFN3, PLXNB3, CD36 and HIC2 mRNA in retina were detected by real-time quantitative polymerase chain reaction. The comparison between the two groups was performed using an unpaired t test. ResultsThe P1 latency of control group and NMDA group were (117.86±6.48) and (148.46±3.78) ms, and the amplitudes were (42.57±2.41) and (8.68±0.63) μV, respectively. Compared with the normal control group, the latency period was prolonged and the amplitude was significantly decreased in the NMDA group, with statistical significance (P＜0.001). In normal control group, retinal ganglion cells (RGC) were uniformly arranged with large round nuclei. In NMDA group, the volume of retinal RGC was atrophied and the number of RGC was reduced. The total retinal thickness in the control group and NMDA group was (207.51±12.76) μm and (187.51±12.54) μm, respectively. The number of β3 tubulin positive cells was 79.86±6.56 and 29.36±2.16, respectively. Compared with normal control group, the total retinal thickness and the number of β3 tubulin positive cells in NMDA group were decreased, with statistical significance (P＜0.001). Compared with the control group, 576 differentially expressed m5C mRNA were screened in the NMDA group, among which 230 up-regulated and 346 down-regulated genes were detected, respectively. The results of biological information analysis showed that compared with the control group, the upregulated m5C mRNA in the NMDA group was mainly involved in biological processes such as perception and cell-cell adhesion, and was mainly concentrated in the cytokine-cytokine receptor interaction and neural active ligand-receptor interaction pathway. The biological processes in which down-regulated m5C mRNA was mainly involved in biological processes such as G-protein-coupled receptor signaling pathway and cell communication, which were mainly concentrated in primary immune deficiency pathway and neural active ligand-receptor interaction pathway. Real-time quantitative polymerase chain reaction detection results showed that compared with the normal control group, the relative expression levels of SLFN3 and PLXNB3 mRNA in the retina of rats in NMDA group were significantly increased, while the relative expression levels of CD36 and HIC2 mRNA were significantly decreased, with statistical significance (P＜0.05). ConclusionIn NMDA induced retinal excitatory toxicity rat models, m5C modified retinal transcriptome showed abnormal expression.