N-methyl-D-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the N-methyl-D-aspartate receptor impairs learning and memory abilities and induces pathological changes in the bra...N-methyl-D-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the N-methyl-D-aspartate receptor impairs learning and memory abilities and induces pathological changes in the brain. Previous studies have paid little attention to the role of the N-methyl-D-aspartate receptor subunit 1 (NR1) in neurogenesis in the hippocampus of schizophrenia. A mouse model of schizophrenia was established by intraperitoneal injection of 0.6 mg/kg MK-801, once a day, for 14 days. In N-methyl-D-aspartate-treated mice, N-methyl-D-aspartate was administered by intracerebroventricular injection in schizophrenia mice on day 15. The number of NR1-, Ki67- or BrdU-immunoreactive cells in the dentate gyrus was measured by immunofluorescence staining. Our data showed the number of NR1-immunoreactive cells increased along with the decreasing numbers of BrdU- and Ki67-immunoreactive cells in the schizophrenia groups compared with the control group. N-methyl-D-aspartate could reverse the above changes. These results indicated that NR1 can regulate neurogenesis in the hippocampal dentate gyrus of schizophrenia mice, supporting NR1 as a promising therapeutic target in the treatment of schizophrenia. This study was approved by the Experimental Animal Ethics Committee of the Ningxia Medical University, China (approval No. 2014-014) on March 6, 2014.展开更多
We report an atypical case of anti-N-methyl-D-aspartate receptor encephalitis(ANMDARE). A 27-year-old man diagnosed with ANMDARE received immunotherapy and had a good recovery. However, within one month, he developed ...We report an atypical case of anti-N-methyl-D-aspartate receptor encephalitis(ANMDARE). A 27-year-old man diagnosed with ANMDARE received immunotherapy and had a good recovery. However, within one month, he developed severe status epilepticus and decreased level of conscience with new hyperpyrexia and dyspnea, and was admitted to the emergency intensive care unit. Acinetobacter baumanii were found in the sputum culture; and anti-NMDAR antibodies were positive(titer: 1/80) in the cerebrospinal fluid. Repeated immunotherapy was administered with antibacterial agents, and the patient recovered except for mild psychiatric sequelae. This is the first report of ANMDARE that aggravates after acinetobacter baumannii pneumonia. Awareness and knowledge of this disorder should be extended, especially in the emergency medicine community.展开更多
Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine.The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior,electroencephalography ...Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine.The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior,electroencephalography and 24-hour survival rate.Propofol（12.5-100 mg/kg） improved status epilepticus in a dose-dependent manner,and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection.Western blot results showed that,24 hours after induction of status epilepticus,the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly increased in rat cerebral cortex and hippocampus.Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels,but not the increase in N-methyl-D-aspartate receptor 2A subunit levels.The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine.This effect may be associated with downregulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures.展开更多
AIM: Many studies have demonstrated N-methyl-D-aspartate receptor-1-subunit (NMDAR1) is associated with amblyopia. The effectiveness of levodopa in improving the visual function of the children with amblyopia has also...AIM: Many studies have demonstrated N-methyl-D-aspartate receptor-1-subunit (NMDAR1) is associated with amblyopia. The effectiveness of levodopa in improving the visual function of the children with amblyopia has also been proved. But the mechanism is undefined. Our study was to explore the possible mechanism. METHODS: Sixty 14-day-old healthy SD rats were randomly divided into 4 groups, including normal group, monocular deprivation group, levodopa group and normal saline group, 15 rats each. We sutured all the rats' unilateral eyelids except normal group to establish the monocular deprivation animal model and raise them in normal sunlight till 45-day-old. NMDAR1 was detected in the visual cortex with immunohistochemistry methods, Western Blot and Real time PCR. LD and NS groups were gavaged with levodopa (40mg/kg) and normal saline for 28 days respectively. NMDAR1 was also detected with the methods above. RESULTS: NMDAR1 in the visual cortex of MD group was less than that of normal group. NMDAR1 in the visual cortex of LD group was more than that of NS group. CONCLUSION: NMDAR1 is associated with the plasticity of visual development. Levodopa may influence the expression of NMDAR1 and improve visual function, and its target may lie in the visual cortex.展开更多
BACKGROUND： Gamma-aminobutyric acid A （GABAA） and N-methyl-D-aspartate （NMDA） receptors are significant receptors in the central nervous system. An understanding of GABAA and NMDA receptor expression in spiral ga...BACKGROUND： Gamma-aminobutyric acid A （GABAA） and N-methyl-D-aspartate （NMDA） receptors are significant receptors in the central nervous system. An understanding of GABAA and NMDA receptor expression in spiral ganglion neurons （SGN） provides information for the functional role of these receptors in the auditory system. OBJECTIVE： To investigate mRNA expression of GABAA receptor （GABAAR） and NMDA receptor （NMDAR） subunits in the rat SGN. DESIGN, TIME AND SETTING： This in vitro, molecular biological study was performed at the Laboratory of Otolaryngology-Head and Neck Surgery, Guangxi Medical University, China from July 2007 to May 2008. MATERIALS： Reverse Transcriptase Kit and Taq DNA polymerase were purchased from Fermentas Burlington, ON, Canada; GABAAR and NMDAR primers were purchased from Shanghai Sangon, Shanghai, China. METHODS： SGN from 3-5 day postnatal Wistar rats was collected for primary cultures, mRNA expression of GABAAR and NMDAR subunits in the SGN was determined by reverse transcription polymerase chain reaction. MAIN OUTCOME MEASURES： Expression levels of GABAAR and NMDAR subunits were determined by quantitative analysis. RESULTS： GABAAR subunits （αl 6, β1 3, and y1 3） and NMDAR subunits （NR1, NR2A, NR2B, NR2C, NR2D, NR3A, and NR3B） were detected in the SGN. In α subunit genes of GABAAR, α1 and α3 expression was similar （P 〉 0.05） and greater than the other subunits. Of the β subunit genes, β1 subunit mRNA levels were greater than β2 and β3. Of the y subunit genes, y2 subunit mRNA levels were greater than y1 and y3. NR1 mRNA expression was the greatest of NMDAR subunits. CONCLUSION： GABAAR subunits （α1 6, β1-3, and y1-3） and NMDAR subunits （NR1, NR2A, NR2B, NR2C, NR2D, NR3A, and NR3B） were expressed in the rat SGN. Through comparison of GABAAR and NMDAR subunit expression, possible GABAAR combinations, as well as highly expressed subunit combinations, were estimated, which provided information for pharmacological and electrophysiological characteristics of GABAAR in the auditory system.展开更多
BACKGROUND： Tanshinone has been previously shown to be involved in the prevention and treatment of cerebral ischemia/reperfusion injury. In addition, excitatory amino acid-mediated neu- rotoxicity may induce neuronal...BACKGROUND： Tanshinone has been previously shown to be involved in the prevention and treatment of cerebral ischemia/reperfusion injury. In addition, excitatory amino acid-mediated neu- rotoxicity may induce neuronal damage following spinal cord ischemia/reperfusion injury. OBJECTIVE： To explore the interventional effect of tanshinone on N-methyl-D-aspartate receptor 1 （NMDAR1） protein expression in a rat model of spinal cord ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized molecular biology experiment was conducted at the Traumatology ＆ Orthopedics Laboratory of Fujian Hospital of Traditional Chinese Medicine （Key Laboratory of State Administration of Traditional Chinese Medicine） between September 2007 and May 2008. MATERIALS： A total of 88 Sprague Dawley rats were randomly divided into a sham operation （n = 8）, model （n = 40）, and tanshinone （n = 40） groups. Thirty minutes after ischemia, rats in the model and tanshinone groups were observed at hour 0.5, 1, 4, 8, and 12 following perfusion, with eight rats for each time point. METHODS： Abdominal aorta occlusion was performed along the right renal arterial root using a Scoville-Lewis clamp to induce spinal cord ischemia. Blood flow was recovered 30 minutes following occlusion to establish models of spinal cord ischemia/reperfusion injury. Abdominal aorta occlusion was not performed in the sham operation group. An intraperitoneal injection of tanshinone ⅡA sulfonic sodium solution （0.2 L/g） was administered to rats in the tanshinone group, preoperatively. In addition, rats in the sham operation and model groups were treated with an intraperitoneal injection of the same concentration of saline, preoperatively. MAIN OUTCOME MEASURES： NMDAR1 protein expression in the anterior horn of the spinal cord, accumulative absorbance, average absorbance, and area of positive cells were detected in the three groups through immunohistochemistry. RESULTS： All 88 rats were included in the final analysis. （1） NMDAR1 protein expression increased following 30-minute ischemia/1-hour reperfusion injury to the spinal cord, and reached a peak 4 hours after reperfusion. （2） Accumulative absorbance and average absorbance of NMDAR1, as well as area of positive cells in the model group, were significantly greater than the sham operation group at each time point （P 〈 0.05）. However, values in the tanshinone group were significantly less than the model group （P 〈 0.05）. CONCLUSION： NMDAR1 protein expression was rapidly increased following spinal cord ischemia/reperfusion injury and reached a peak 4 hours following reperfusion. In addition, tanshinone downregulated NMDAR1 protein expression in the anterior horn of the spinal cord.展开更多
Previous studies have shown that mitogen-activated protein kinase （MAPK） signaling pathways are involved in N-methyI-D-aspartate （NMDA）-mediated excitotoxicity. However, a systematic observation or analysis of the...Previous studies have shown that mitogen-activated protein kinase （MAPK） signaling pathways are involved in N-methyI-D-aspartate （NMDA）-mediated excitotoxicity. However, a systematic observation or analysis of the role of these various MAPK pathways in excitotoxicity processes does not exist. The present study further evaluated the role and contribution of three MAPK pathways extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK in an NMDA-mediated excitotoxicity model using MAPK^specific inhibitor. Results demonstrated that c-Jun N-terminal kinase inhibitor SP600125 and/or p38 MAPK inhibitor SB203580 inhibited NMDA-induced reduction in cell viability, as well as reduced NMDA-induced lactate dehydrogenase leakage and reactive oxygen species production. However, PD98059, an inhibitor of extracellular signal-regulated kinase, did not influence this model. Results demonstrated an involvement of c-Jun N-terminal kinase and p38 MAPK, but not extracellular signal-regulated kinase, in NMDA-mediated excitotoxicity in cortical neurons.展开更多
Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1（NMDAR1） plays an important role in t...Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1（NMDAR1） plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D（-）-2-amino-5-phosphonopentanoic acid（AP-5）,or both once daily for 15 days.Compared with injured drug na？ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity（as assessed by immunohistochemistry） and protein（as determined by western blot assay） in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.展开更多
Clinical and animal experiments have proved that intrathecal injection of butorphanol has an analgesic effect. However, whether the analgesic effect is associated with activation of the N-methyI-D-aspartate （NMDA） r...Clinical and animal experiments have proved that intrathecal injection of butorphanol has an analgesic effect. However, whether the analgesic effect is associated with activation of the N-methyI-D-aspartate （NMDA） receptor remains unclear. This study presumed that intrathecal injection of butorphanol has an analgesic effect on formalin-induced inflammatory pain in rats, and its analgesic effect is associated with inhibition of NMDA receptors. Concurrently, ketamine was injected into the intrathecal space, which is a non-competitive NMDA receptor antagonist, to determine the analgesic mechanism of butorphanol. The total reflection time in phase 1 and phase 2 of rat hind paws carding action was reduced when the butorphanol dose was increased to 25 μg, or a low dose of butorphanol was combined with ketamine. Intrathecal injection of a high dose of butorphanol alone or a low dose of butorphanol combined with ketamine can remarkably reduce NMDA receptor expression in the Ls spinal dorsal hom of formalin-induced pain rats. The results suggest that intrathecal injection of butorphanol has analgesic effects on formalin-induced inflammatory pain, and remarkably reduces NMDA receptor expression in the rat spinal dorsal horn Ketamine strengthens this analgesic effect. The analgesic mechanism of intrathecal injection of butorphanol is associated with inhibition of NMDA receptor activation.展开更多
ANTI-N-METHYL-D-ASPARTATE (NMDA) receptorencephalitis is a newly recognized autoimmunedisease. It is predominantly described in youngwomen with a series of symptoms, includingpersonality change, memory loss, seizures,...ANTI-N-METHYL-D-ASPARTATE (NMDA) receptorencephalitis is a newly recognized autoimmunedisease. It is predominantly described in youngwomen with a series of symptoms, includingpersonality change, memory loss, seizures, involuntarymovements, autonomic dysfunction et al.1 It is commonlyassociated with mature ovarian teratomas.2 Since its firstdenomination by Dalmau et al,1 many scientific publicationshave emerged on anti-NMDA receptor encephalitis, butonly a few focused on the anesthetic management ofpatients with this disease.3-5 Herein we reported two caseswith anti-NMDA receptor encephalitis in association withovarian teratoma and discussed the anesthetic managementand the outcomes of these patients.展开更多
Previous reports have shown that N-methyl-D-aspartate （NMDA） receptors are extensively involved in epilepsy genesis and recurrence. Recent studies have shown that synaptic and extrasynaptic NMDA receptors play diffe...Previous reports have shown that N-methyl-D-aspartate （NMDA） receptors are extensively involved in epilepsy genesis and recurrence. Recent studies have shown that synaptic and extrasynaptic NMDA receptors play different, or even opposing, roles in various signaling pathways, including synaptic plasticity and neuronal death. The present study analyzed changes in synaptic and extrasynaptic NMDA receptor-mediated currents during epilepsy onset. Mouse models of lithium chloride pilocarpLne-induced epilepsy were established, and hippocampal slices were prepared at 24 hours after the onset of status epilepticus. Synaptic and extrasynaptic NMDA receptor-mediated excitatory post-synaptic currents （NMDA-EPSCs） were recorded in CA1 pyramidal neurons by whole-cell patch clamp technique. Results demonstrated no significant difference in rise and delay time of synaptic NMDA-EPSCs compared with normal neurons. Peak amplitude, area-to-peak ratio, and rising time of extrasynaptic NMDA-EPSCs remained unchanged, but decay of extrasynaptic NMDA-EPSCs was faster than that of normal neurons, These results suggest that extrasynaptic NMDA receptors play a role in epileptogenesis.展开更多
In normal rat forebrain, the NR1/NR2A and NR1/NR2B dimmers are the main constitutional forms of NMDA receptors. The present study was carried out to determine the functional properties of the heteromeric NMDA receptor...In normal rat forebrain, the NR1/NR2A and NR1/NR2B dimmers are the main constitutional forms of NMDA receptors. The present study was carried out to determine the functional properties of the heteromeric NMDA receptor subunits and their inhibition by bis(7)-tacrine (B7T). Rat NR1, NR2A and NR2B cDNAs were transfected into human embryonic kidney 293 cells (HEK-293).The inhibition of NMDA-activated currents by B7T was detected in HEK-293 cell expressing NR1/NR2A or NR1/NR2B receptors by using whole-cell patch-clamp techniques. The results showed that in HEK-293 cells expressing NR1/NR2A receptor, 1μmol/L B7T inhibited 30μmol/L NMDA- and 1000μmol/L NMDA-activated steady-state currents by 46% and 40%, respectively (P>0.05; n=5), suggesting that the inhibition of B7T on NR1/NR2A receptor doesn’t depend on NMDA concentration, which is consistent with a non-competitive mechanism of inhibition. But for the NR1/NR2B receptor, 1μmol/L B7T inhibited 30μmol/L NMDA- and 1000 μmol/L NMDA-activated steady-state currents by 61% and 13%, re-spectively (P<0.05; n=6), showing that B7T appears to be competitive with NMDA. In addition, simultaneous application of 1μmol/L B7T and 1000μmol/L NMDA produced a moderate inhibition of peak NMDA-activated current, followed by a gradual decline of the current to a steady state. However, the gradual onset of inhibition produced by B7T applied simultaneously with NMDA was eliminated when B7T was given 5s before NMDA. These results suggested that B7T inhibition of NMDA current mediated by NR1/NR2B receptor was slow onset, and it did not depend on the presence of the agonist. With holding potentials ranging from -50 to +50 mV, the B7T inhibition rate of NMDA currents didn’t change significantly, and neither did the reversal potential. We are led to conclude that the NR1/NR2B recombinant receptor can serve as a very useful model for studying the molecular mechanism of NMDA receptor inhibition by B7T.展开更多
This study investigated the effects of daily intraperitoneal injections of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine （L-NA） on the survival of retinal gangl...This study investigated the effects of daily intraperitoneal injections of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine （L-NA） on the survival of retinal ganglion cells （RGCs） at 1 and 2 weeks after unilateral optic nerve transection in adult hamsters. The left optic nerves of all animals were transected intraorbitally 1 mm from the optic disc and RGCs were retrogradely labeled with Fluorogold before they received different daily dosages of single MK-801 or L-NA as well as daily combinational treatments of these two chemicals. All experimental and control animals survived for 1 or 2 weeks after optic nerve transection. Our results revealed that the mean numbers of surviving RGCs increased and then decreased when the dosage of MK-801 （1.0, 3.0 and 4.5 mg/kg） and L-NA （1.5, 3.0, 4.5 and 6.0 mg/kg） increased at both 1 and 2 weeks survival time points. Daily combinational use of 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA lead to a highest RGC number that was even higher than the sum of the RGC numbers in 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA subgroups at 2 weeks. These findings indicated that both MK-801 and L-NA can protect axotomized RGCs in a dose-dependent manner and combinational treatment of these chemicals possesses a potentiative and protective effect.展开更多
In the present study, 7 day postnatal C57/BL6 wild-type mice （hyperoxia group） and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice （NR3A KO group） were exposed to 75% oxygen and 15% nitrogen...In the present study, 7 day postnatal C57/BL6 wild-type mice （hyperoxia group） and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice （NR3A KO group） were exposed to 75% oxygen and 15% nitrogen in a closed container for 5 days. Wild-type mice raised in normoxia served as controls. TdT-mediated dUTP nick end labeling （TUNEL）/neuron-specific nuclear protein （NeuN） and 5-bromo-2＇-deoxyuridine （BrdU）/NeuN immunofluorescence staining showed that the number of apoptotic cells and the number of proliferative cells in the dentate subgranular zone significantly increased in the hyperoxia group compared with the control group. However, in the same hyperoxia environment, the number of apoptotic cells and the number of proliferative cells significantly decreased in the NR3A KO group compared with hyperoxia group. TUNEL＋/NeuN＋ and BrdU＋/NeuN~ cells were observed in the NR3A KO and the hyperoxia groups. These results demonstrated that the NR3A gene can promote cell apoptosis and mediate the potential damage in the developing brain induced by exposure to non-physiologically high concentrations of oxygen.展开更多
BACKGROUND： Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated...BACKGROUND： Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE： To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY： A computer-based online search was conducted in PUBMED for English language publications containing the key words ＂brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor＂ from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria： ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria： duplicated articles. LITERATURE EVALUATION： References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS： After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these factors change at different time points after brain injury, and what is the relationship between associated factors and cognitive disorder. CONCLUSION： It is necessary to comprehensively study some associated factors, to analyze their changes and their relationship with cognitive disorder following brain injury, and to investigate their effects at different time points after brain injury.展开更多
基金supported by the National Natural Science Foundation of China,No.81160169(to JL),81460214(to JL),31660270(to JD),31460255(to JD)the Natural Science Foundation of Ningxia Hui Autonomous Region of China,No.2018AAC02005(to JL)
文摘N-methyl-D-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the N-methyl-D-aspartate receptor impairs learning and memory abilities and induces pathological changes in the brain. Previous studies have paid little attention to the role of the N-methyl-D-aspartate receptor subunit 1 (NR1) in neurogenesis in the hippocampus of schizophrenia. A mouse model of schizophrenia was established by intraperitoneal injection of 0.6 mg/kg MK-801, once a day, for 14 days. In N-methyl-D-aspartate-treated mice, N-methyl-D-aspartate was administered by intracerebroventricular injection in schizophrenia mice on day 15. The number of NR1-, Ki67- or BrdU-immunoreactive cells in the dentate gyrus was measured by immunofluorescence staining. Our data showed the number of NR1-immunoreactive cells increased along with the decreasing numbers of BrdU- and Ki67-immunoreactive cells in the schizophrenia groups compared with the control group. N-methyl-D-aspartate could reverse the above changes. These results indicated that NR1 can regulate neurogenesis in the hippocampal dentate gyrus of schizophrenia mice, supporting NR1 as a promising therapeutic target in the treatment of schizophrenia. This study was approved by the Experimental Animal Ethics Committee of the Ningxia Medical University, China (approval No. 2014-014) on March 6, 2014.
文摘We report an atypical case of anti-N-methyl-D-aspartate receptor encephalitis(ANMDARE). A 27-year-old man diagnosed with ANMDARE received immunotherapy and had a good recovery. However, within one month, he developed severe status epilepticus and decreased level of conscience with new hyperpyrexia and dyspnea, and was admitted to the emergency intensive care unit. Acinetobacter baumanii were found in the sputum culture; and anti-NMDAR antibodies were positive(titer: 1/80) in the cerebrospinal fluid. Repeated immunotherapy was administered with antibacterial agents, and the patient recovered except for mild psychiatric sequelae. This is the first report of ANMDARE that aggravates after acinetobacter baumannii pneumonia. Awareness and knowledge of this disorder should be extended, especially in the emergency medicine community.
基金supported by National Natural Science Foundation of China,No. 30500482
文摘Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine.The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior,electroencephalography and 24-hour survival rate.Propofol（12.5-100 mg/kg） improved status epilepticus in a dose-dependent manner,and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection.Western blot results showed that,24 hours after induction of status epilepticus,the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly increased in rat cerebral cortex and hippocampus.Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels,but not the increase in N-methyl-D-aspartate receptor 2A subunit levels.The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine.This effect may be associated with downregulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures.
文摘AIM: Many studies have demonstrated N-methyl-D-aspartate receptor-1-subunit (NMDAR1) is associated with amblyopia. The effectiveness of levodopa in improving the visual function of the children with amblyopia has also been proved. But the mechanism is undefined. Our study was to explore the possible mechanism. METHODS: Sixty 14-day-old healthy SD rats were randomly divided into 4 groups, including normal group, monocular deprivation group, levodopa group and normal saline group, 15 rats each. We sutured all the rats' unilateral eyelids except normal group to establish the monocular deprivation animal model and raise them in normal sunlight till 45-day-old. NMDAR1 was detected in the visual cortex with immunohistochemistry methods, Western Blot and Real time PCR. LD and NS groups were gavaged with levodopa (40mg/kg) and normal saline for 28 days respectively. NMDAR1 was also detected with the methods above. RESULTS: NMDAR1 in the visual cortex of MD group was less than that of normal group. NMDAR1 in the visual cortex of LD group was more than that of NS group. CONCLUSION: NMDAR1 is associated with the plasticity of visual development. Levodopa may influence the expression of NMDAR1 and improve visual function, and its target may lie in the visual cortex.
基金the National Natural Science Foundation of China,No. 30560162the Natural Scientific Foundation of Guangxi Zhuang Autonomous Region,No.0542087Guangxi Health and Medical Community Scientific Research,No.200512
文摘BACKGROUND： Gamma-aminobutyric acid A （GABAA） and N-methyl-D-aspartate （NMDA） receptors are significant receptors in the central nervous system. An understanding of GABAA and NMDA receptor expression in spiral ganglion neurons （SGN） provides information for the functional role of these receptors in the auditory system. OBJECTIVE： To investigate mRNA expression of GABAA receptor （GABAAR） and NMDA receptor （NMDAR） subunits in the rat SGN. DESIGN, TIME AND SETTING： This in vitro, molecular biological study was performed at the Laboratory of Otolaryngology-Head and Neck Surgery, Guangxi Medical University, China from July 2007 to May 2008. MATERIALS： Reverse Transcriptase Kit and Taq DNA polymerase were purchased from Fermentas Burlington, ON, Canada; GABAAR and NMDAR primers were purchased from Shanghai Sangon, Shanghai, China. METHODS： SGN from 3-5 day postnatal Wistar rats was collected for primary cultures, mRNA expression of GABAAR and NMDAR subunits in the SGN was determined by reverse transcription polymerase chain reaction. MAIN OUTCOME MEASURES： Expression levels of GABAAR and NMDAR subunits were determined by quantitative analysis. RESULTS： GABAAR subunits （αl 6, β1 3, and y1 3） and NMDAR subunits （NR1, NR2A, NR2B, NR2C, NR2D, NR3A, and NR3B） were detected in the SGN. In α subunit genes of GABAAR, α1 and α3 expression was similar （P 〉 0.05） and greater than the other subunits. Of the β subunit genes, β1 subunit mRNA levels were greater than β2 and β3. Of the y subunit genes, y2 subunit mRNA levels were greater than y1 and y3. NR1 mRNA expression was the greatest of NMDAR subunits. CONCLUSION： GABAAR subunits （α1 6, β1-3, and y1-3） and NMDAR subunits （NR1, NR2A, NR2B, NR2C, NR2D, NR3A, and NR3B） were expressed in the rat SGN. Through comparison of GABAAR and NMDAR subunit expression, possible GABAAR combinations, as well as highly expressed subunit combinations, were estimated, which provided information for pharmacological and electrophysiological characteristics of GABAAR in the auditory system.
基金the National Natural Science Foundation of China, No. 30572401 the National Natural Science Foundation of Fujian Province, No. C0510023 the Project for Academic Human Resources Development in Fujian Province, No. 1401
文摘BACKGROUND： Tanshinone has been previously shown to be involved in the prevention and treatment of cerebral ischemia/reperfusion injury. In addition, excitatory amino acid-mediated neu- rotoxicity may induce neuronal damage following spinal cord ischemia/reperfusion injury. OBJECTIVE： To explore the interventional effect of tanshinone on N-methyl-D-aspartate receptor 1 （NMDAR1） protein expression in a rat model of spinal cord ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized molecular biology experiment was conducted at the Traumatology ＆ Orthopedics Laboratory of Fujian Hospital of Traditional Chinese Medicine （Key Laboratory of State Administration of Traditional Chinese Medicine） between September 2007 and May 2008. MATERIALS： A total of 88 Sprague Dawley rats were randomly divided into a sham operation （n = 8）, model （n = 40）, and tanshinone （n = 40） groups. Thirty minutes after ischemia, rats in the model and tanshinone groups were observed at hour 0.5, 1, 4, 8, and 12 following perfusion, with eight rats for each time point. METHODS： Abdominal aorta occlusion was performed along the right renal arterial root using a Scoville-Lewis clamp to induce spinal cord ischemia. Blood flow was recovered 30 minutes following occlusion to establish models of spinal cord ischemia/reperfusion injury. Abdominal aorta occlusion was not performed in the sham operation group. An intraperitoneal injection of tanshinone ⅡA sulfonic sodium solution （0.2 L/g） was administered to rats in the tanshinone group, preoperatively. In addition, rats in the sham operation and model groups were treated with an intraperitoneal injection of the same concentration of saline, preoperatively. MAIN OUTCOME MEASURES： NMDAR1 protein expression in the anterior horn of the spinal cord, accumulative absorbance, average absorbance, and area of positive cells were detected in the three groups through immunohistochemistry. RESULTS： All 88 rats were included in the final analysis. （1） NMDAR1 protein expression increased following 30-minute ischemia/1-hour reperfusion injury to the spinal cord, and reached a peak 4 hours after reperfusion. （2） Accumulative absorbance and average absorbance of NMDAR1, as well as area of positive cells in the model group, were significantly greater than the sham operation group at each time point （P 〈 0.05）. However, values in the tanshinone group were significantly less than the model group （P 〈 0.05）. CONCLUSION： NMDAR1 protein expression was rapidly increased following spinal cord ischemia/reperfusion injury and reached a peak 4 hours following reperfusion. In addition, tanshinone downregulated NMDAR1 protein expression in the anterior horn of the spinal cord.
基金supported by the Scientific and Technical Innovation Fund of Shanxi Medical University,No.01200802Shanxi Province Foundation for Returnees,No.2007-43
文摘Previous studies have shown that mitogen-activated protein kinase （MAPK） signaling pathways are involved in N-methyI-D-aspartate （NMDA）-mediated excitotoxicity. However, a systematic observation or analysis of the role of these various MAPK pathways in excitotoxicity processes does not exist. The present study further evaluated the role and contribution of three MAPK pathways extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK in an NMDA-mediated excitotoxicity model using MAPK^specific inhibitor. Results demonstrated that c-Jun N-terminal kinase inhibitor SP600125 and/or p38 MAPK inhibitor SB203580 inhibited NMDA-induced reduction in cell viability, as well as reduced NMDA-induced lactate dehydrogenase leakage and reactive oxygen species production. However, PD98059, an inhibitor of extracellular signal-regulated kinase, did not influence this model. Results demonstrated an involvement of c-Jun N-terminal kinase and p38 MAPK, but not extracellular signal-regulated kinase, in NMDA-mediated excitotoxicity in cortical neurons.
基金supported by the Youth Shihezi University Applied Basic Research Project of China,No.2015ZRKYQ-LH19
文摘Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1（NMDAR1） plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D（-）-2-amino-5-phosphonopentanoic acid（AP-5）,or both once daily for 15 days.Compared with injured drug na？ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity（as assessed by immunohistochemistry） and protein（as determined by western blot assay） in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.
基金a Grant from Department of Science and Technology of Hunan Prov-ince, No. 2009SK3112a Grant from Department of Health of Hunan Province, No. C2008005
文摘Clinical and animal experiments have proved that intrathecal injection of butorphanol has an analgesic effect. However, whether the analgesic effect is associated with activation of the N-methyI-D-aspartate （NMDA） receptor remains unclear. This study presumed that intrathecal injection of butorphanol has an analgesic effect on formalin-induced inflammatory pain in rats, and its analgesic effect is associated with inhibition of NMDA receptors. Concurrently, ketamine was injected into the intrathecal space, which is a non-competitive NMDA receptor antagonist, to determine the analgesic mechanism of butorphanol. The total reflection time in phase 1 and phase 2 of rat hind paws carding action was reduced when the butorphanol dose was increased to 25 μg, or a low dose of butorphanol was combined with ketamine. Intrathecal injection of a high dose of butorphanol alone or a low dose of butorphanol combined with ketamine can remarkably reduce NMDA receptor expression in the Ls spinal dorsal hom of formalin-induced pain rats. The results suggest that intrathecal injection of butorphanol has analgesic effects on formalin-induced inflammatory pain, and remarkably reduces NMDA receptor expression in the rat spinal dorsal horn Ketamine strengthens this analgesic effect. The analgesic mechanism of intrathecal injection of butorphanol is associated with inhibition of NMDA receptor activation.
文摘ANTI-N-METHYL-D-ASPARTATE (NMDA) receptorencephalitis is a newly recognized autoimmunedisease. It is predominantly described in youngwomen with a series of symptoms, includingpersonality change, memory loss, seizures, involuntarymovements, autonomic dysfunction et al.1 It is commonlyassociated with mature ovarian teratomas.2 Since its firstdenomination by Dalmau et al,1 many scientific publicationshave emerged on anti-NMDA receptor encephalitis, butonly a few focused on the anesthetic management ofpatients with this disease.3-5 Herein we reported two caseswith anti-NMDA receptor encephalitis in association withovarian teratoma and discussed the anesthetic managementand the outcomes of these patients.
基金Shanghai Pujiang Program,No. 06PJ14053the National Natural Science Foundation of China,No. 30600177+2 种基金the Scientific Research Founda-tion for the Returned Over-seas Chinese Scholars,State Education MinistryDoctoral Fund of Ministry of Education of China,No. 20070248083Shanghai Leading Aca-demic Discipline Project,No. B205
文摘Previous reports have shown that N-methyl-D-aspartate （NMDA） receptors are extensively involved in epilepsy genesis and recurrence. Recent studies have shown that synaptic and extrasynaptic NMDA receptors play different, or even opposing, roles in various signaling pathways, including synaptic plasticity and neuronal death. The present study analyzed changes in synaptic and extrasynaptic NMDA receptor-mediated currents during epilepsy onset. Mouse models of lithium chloride pilocarpLne-induced epilepsy were established, and hippocampal slices were prepared at 24 hours after the onset of status epilepticus. Synaptic and extrasynaptic NMDA receptor-mediated excitatory post-synaptic currents （NMDA-EPSCs） were recorded in CA1 pyramidal neurons by whole-cell patch clamp technique. Results demonstrated no significant difference in rise and delay time of synaptic NMDA-EPSCs compared with normal neurons. Peak amplitude, area-to-peak ratio, and rising time of extrasynaptic NMDA-EPSCs remained unchanged, but decay of extrasynaptic NMDA-EPSCs was faster than that of normal neurons, These results suggest that extrasynaptic NMDA receptors play a role in epileptogenesis.
基金supported by grants from the National Natural Science Foundation of China(No. 30970927)the Natural Science Foundation of Hubei Province, China(No.2008CDA053)the Wuhan Science and Technology Foundation(Nos.200970634270,201250499145-27 and 20115069-9189-23)
文摘In normal rat forebrain, the NR1/NR2A and NR1/NR2B dimmers are the main constitutional forms of NMDA receptors. The present study was carried out to determine the functional properties of the heteromeric NMDA receptor subunits and their inhibition by bis(7)-tacrine (B7T). Rat NR1, NR2A and NR2B cDNAs were transfected into human embryonic kidney 293 cells (HEK-293).The inhibition of NMDA-activated currents by B7T was detected in HEK-293 cell expressing NR1/NR2A or NR1/NR2B receptors by using whole-cell patch-clamp techniques. The results showed that in HEK-293 cells expressing NR1/NR2A receptor, 1μmol/L B7T inhibited 30μmol/L NMDA- and 1000μmol/L NMDA-activated steady-state currents by 46% and 40%, respectively (P>0.05; n=5), suggesting that the inhibition of B7T on NR1/NR2A receptor doesn’t depend on NMDA concentration, which is consistent with a non-competitive mechanism of inhibition. But for the NR1/NR2B receptor, 1μmol/L B7T inhibited 30μmol/L NMDA- and 1000 μmol/L NMDA-activated steady-state currents by 61% and 13%, re-spectively (P<0.05; n=6), showing that B7T appears to be competitive with NMDA. In addition, simultaneous application of 1μmol/L B7T and 1000μmol/L NMDA produced a moderate inhibition of peak NMDA-activated current, followed by a gradual decline of the current to a steady state. However, the gradual onset of inhibition produced by B7T applied simultaneously with NMDA was eliminated when B7T was given 5s before NMDA. These results suggested that B7T inhibition of NMDA current mediated by NR1/NR2B receptor was slow onset, and it did not depend on the presence of the agonist. With holding potentials ranging from -50 to +50 mV, the B7T inhibition rate of NMDA currents didn’t change significantly, and neither did the reversal potential. We are led to conclude that the NR1/NR2B recombinant receptor can serve as a very useful model for studying the molecular mechanism of NMDA receptor inhibition by B7T.
基金supported by research grants from Chinese National Key Project for Basic Research,No. 2011CB504402the National Natural Science Foundation of China, No. 30901649 and 30872829
文摘This study investigated the effects of daily intraperitoneal injections of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine （L-NA） on the survival of retinal ganglion cells （RGCs） at 1 and 2 weeks after unilateral optic nerve transection in adult hamsters. The left optic nerves of all animals were transected intraorbitally 1 mm from the optic disc and RGCs were retrogradely labeled with Fluorogold before they received different daily dosages of single MK-801 or L-NA as well as daily combinational treatments of these two chemicals. All experimental and control animals survived for 1 or 2 weeks after optic nerve transection. Our results revealed that the mean numbers of surviving RGCs increased and then decreased when the dosage of MK-801 （1.0, 3.0 and 4.5 mg/kg） and L-NA （1.5, 3.0, 4.5 and 6.0 mg/kg） increased at both 1 and 2 weeks survival time points. Daily combinational use of 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA lead to a highest RGC number that was even higher than the sum of the RGC numbers in 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA subgroups at 2 weeks. These findings indicated that both MK-801 and L-NA can protect axotomized RGCs in a dose-dependent manner and combinational treatment of these chemicals possesses a potentiative and protective effect.
基金supported by the National Institutes of Health, USA, No. NS 045810, NS 057255the BasicClinical Scientific Research Foundation Program of the Capital Medical University, China, No. 2006JL19
文摘In the present study, 7 day postnatal C57/BL6 wild-type mice （hyperoxia group） and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice （NR3A KO group） were exposed to 75% oxygen and 15% nitrogen in a closed container for 5 days. Wild-type mice raised in normoxia served as controls. TdT-mediated dUTP nick end labeling （TUNEL）/neuron-specific nuclear protein （NeuN） and 5-bromo-2＇-deoxyuridine （BrdU）/NeuN immunofluorescence staining showed that the number of apoptotic cells and the number of proliferative cells in the dentate subgranular zone significantly increased in the hyperoxia group compared with the control group. However, in the same hyperoxia environment, the number of apoptotic cells and the number of proliferative cells significantly decreased in the NR3A KO group compared with hyperoxia group. TUNEL＋/NeuN＋ and BrdU＋/NeuN~ cells were observed in the NR3A KO and the hyperoxia groups. These results demonstrated that the NR3A gene can promote cell apoptosis and mediate the potential damage in the developing brain induced by exposure to non-physiologically high concentrations of oxygen.
基金the grantsfrom Fujian Science and Technology Bureau, No.2006Y0012
文摘BACKGROUND： Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE： To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY： A computer-based online search was conducted in PUBMED for English language publications containing the key words ＂brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor＂ from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria： ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria： duplicated articles. LITERATURE EVALUATION： References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS： After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these factors change at different time points after brain injury, and what is the relationship between associated factors and cognitive disorder. CONCLUSION： It is necessary to comprehensively study some associated factors, to analyze their changes and their relationship with cognitive disorder following brain injury, and to investigate their effects at different time points after brain injury.
