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
Objective: To observe and elucidate the neuroprotective effect of Xingnaojing (XNJ) injection on hippocampal N-methyl-D-aspartic acid (NMDA) receptors of focal cerebral ischemia in rats. Methods: Cerebral ischemia was...Objective: To observe and elucidate the neuroprotective effect of Xingnaojing (XNJ) injection on hippocampal N-methyl-D-aspartic acid (NMDA) receptors of focal cerebral ischemia in rats. Methods: Cerebral ischemia was established by occluding the middle cerebral artery with an intraluminal suture technique in rats. Neurological deficit score, infarct volume and quantity of NMDA receptors were estimated in all groups and compared. Results: After being treated with XNJ, the score decreased in the initial 6 hours and infarct volume decreased in 24 hours. And within 24 hours, the quantity of NMDA receptors obviously decreased compared with the model group (P<0. 01) It indicated that XNJ could ameliorate neurological behavior of middle cerebral artery occlusion rats and down-regulate the expression of hippocampal NMDA receptors. Conclusion: The neuroprotective effect of XNJ on focal cerebral ischemia is possibly related to down-regulating the expression of NMDA receptors in rats.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
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
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
Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B (NR2B) overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA (siRNA) can inhibit NR2B e...Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B (NR2B) overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA (siRNA) can inhibit NR2B expression, siRNA may provide a novel approach to treat neuropathic pain and possibly nerve injury. However, an efficient and safe vector for NR2B siRNA has not been discovered. This study shows that a water soluble lipopolymer (WSLP) comprised of low molecular weight polyethyleneimine (PEI) and cholesterol can deliver siRNA targeting NR2B for the treatment of neuropathic pain. Results show that intrathecal injection of WSLP/siRNA complexes for 3 days inhibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%, respectively, compared with control rats (P 〈 0.01). Injection of WSLP complexed with scrambled siRNA, or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP/siRNA complexes significantly relieved neuropathic pain at 3, 7, 12, and 21 days, while injection of WSLP with scrambled siRNA or PEI with siRNA did not. These results demonstrate that WSLP can efficiently deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.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
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 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
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
The latencies of motor- and somatosensory-evoked potentials were prolonged to different degrees, and wave amplitude was obviously decreased, after injection of dynorphin into the rat subarachnoid cavity. The wave ampl...The latencies of motor- and somatosensory-evoked potentials were prolonged to different degrees, and wave amplitude was obviously decreased, after injection of dynorphin into the rat subarachnoid cavity. The wave amplitude and latencies of motor- and somatosensory-evoked potentials were significantly recovered at 7 and 14 days after combined injection of dynorphin and either the kappa opioid receptor antagonist nor-binaltorphimine or the N-methyl-D-aspartate receptor antagonist MK-801. The wave amplitude and latency were similar in rats after combined injection of dynorphin and nor-binaltorphimine or MK-801. These results suggest that intrathecal injection of dynorphin causes damage to spinal cord function. Prevention of N-methyl-D-aspartate receptor or kappa receptor activation lessened the injury to spinal cord function induced by dynorphin.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
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
Amperometric studies have indicated that substance P as well as NMDA stimulates release of NO in rat aortic rings. These data have been confirmed by functional observations of vaso-relaxant action of NMDA within norad...Amperometric studies have indicated that substance P as well as NMDA stimulates release of NO in rat aortic rings. These data have been confirmed by functional observations of vaso-relaxant action of NMDA within noradrenaline pre-contracted aortic rings, supporting the presence of NMDA receptor in rat aortic rings. It is known that the enzyme endothelial NO synthase (eNOS) mediates vasodilatation not only in rats, but also in C57BL6 mice aortic ring, indicating that in this blood vessel NO is the endogenous endothelium-derived vasodilator. In this work, amperometry together with specifically nitrites insensitive micro-biosensors have been applied to examine the effect of NMDA and substance P upon NO release in rat and in two strains of mice aortic rings. The electrochemical data monitored demonstrate that NMDA mediates vascular relaxation via NO in rats but not in mice. These results are supported by functional data, therefore they suggest that NMDA receptors are “not responding” within these experimental conditions in mice aortic rings.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.
基金Provided financial assistance by"Hundred Talented Projects"of Shanghai Health Bureau (No. 97BR016)
文摘Objective: To observe and elucidate the neuroprotective effect of Xingnaojing (XNJ) injection on hippocampal N-methyl-D-aspartic acid (NMDA) receptors of focal cerebral ischemia in rats. Methods: Cerebral ischemia was established by occluding the middle cerebral artery with an intraluminal suture technique in rats. Neurological deficit score, infarct volume and quantity of NMDA receptors were estimated in all groups and compared. Results: After being treated with XNJ, the score decreased in the initial 6 hours and infarct volume decreased in 24 hours. And within 24 hours, the quantity of NMDA receptors obviously decreased compared with the model group (P<0. 01) It indicated that XNJ could ameliorate neurological behavior of middle cerebral artery occlusion rats and down-regulate the expression of hippocampal NMDA receptors. Conclusion: The neuroprotective effect of XNJ on focal cerebral ischemia is possibly related to down-regulating the expression of NMDA receptors in rats.
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.
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 Natural Science Foundation of Guangdong Province,No.07000059the Science and Technology Development Program of Guangzhou,No.2010Y1-C301the Science and Technology Development Program of Guangdong Province,No.2010B031600123
文摘Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B (NR2B) overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA (siRNA) can inhibit NR2B expression, siRNA may provide a novel approach to treat neuropathic pain and possibly nerve injury. However, an efficient and safe vector for NR2B siRNA has not been discovered. This study shows that a water soluble lipopolymer (WSLP) comprised of low molecular weight polyethyleneimine (PEI) and cholesterol can deliver siRNA targeting NR2B for the treatment of neuropathic pain. Results show that intrathecal injection of WSLP/siRNA complexes for 3 days inhibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%, respectively, compared with control rats (P 〈 0.01). Injection of WSLP complexed with scrambled siRNA, or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP/siRNA complexes significantly relieved neuropathic pain at 3, 7, 12, and 21 days, while injection of WSLP with scrambled siRNA or PEI with siRNA did not. These results demonstrate that WSLP can efficiently deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.
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.
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 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Key Science and Technology Research and Development Program of Liaoning Province, China, No. 20112250021, 20112250041.
文摘The latencies of motor- and somatosensory-evoked potentials were prolonged to different degrees, and wave amplitude was obviously decreased, after injection of dynorphin into the rat subarachnoid cavity. The wave amplitude and latencies of motor- and somatosensory-evoked potentials were significantly recovered at 7 and 14 days after combined injection of dynorphin and either the kappa opioid receptor antagonist nor-binaltorphimine or the N-methyl-D-aspartate receptor antagonist MK-801. The wave amplitude and latency were similar in rats after combined injection of dynorphin and nor-binaltorphimine or MK-801. These results suggest that intrathecal injection of dynorphin causes damage to spinal cord function. Prevention of N-methyl-D-aspartate receptor or kappa receptor activation lessened the injury to spinal cord function induced by dynorphin.
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.
文摘Amperometric studies have indicated that substance P as well as NMDA stimulates release of NO in rat aortic rings. These data have been confirmed by functional observations of vaso-relaxant action of NMDA within noradrenaline pre-contracted aortic rings, supporting the presence of NMDA receptor in rat aortic rings. It is known that the enzyme endothelial NO synthase (eNOS) mediates vasodilatation not only in rats, but also in C57BL6 mice aortic ring, indicating that in this blood vessel NO is the endogenous endothelium-derived vasodilator. In this work, amperometry together with specifically nitrites insensitive micro-biosensors have been applied to examine the effect of NMDA and substance P upon NO release in rat and in two strains of mice aortic rings. The electrochemical data monitored demonstrate that NMDA mediates vascular relaxation via NO in rats but not in mice. These results are supported by functional data, therefore they suggest that NMDA receptors are “not responding” within these experimental conditions in mice aortic rings.
文摘目的探究自身免疫性脑炎(autoimmune encephalitis,AE)患者的脑脊液(cerebral spinal fluid,CSF)细胞学特点。方法回顾性收集济宁医学院附属医院2016年1月至2019年6月收治的28例确诊AE患者的脑脊液常规、生化、细胞学、颅内压等结果,分析其特点及其与疾病严重程度的相关性。结果28例AE患者中,抗N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)脑炎11例,抗富含亮氨酸胶质瘤失活蛋白1(leucine-rich glioma-inactivated protein 1,LGI1)抗体相关脑炎13例,抗γ-氨基丁酸B型受体(γ-aminobutyric acid type B receptor,GABA BR)抗体相关脑炎4例。CSF检查中,颅内压中位数(四分位数间距)为127.5(41.0)mmH 2O,蛋白中位数(四分位数间距)为0.48(0.15)g/L,糖和氯化物基本正常。28例中,7例患者CSF常规检查可见炎性反应;9例患者CSF细胞学检查可见炎性反应,其中6例为抗NMDAR脑炎患者,炎性反应类型均为淋巴细胞炎性反应,轻、中、重度炎性反应分别为4、3、2例,检测到激活淋巴细胞4例,浆细胞2例。CSF细胞学检查炎性细胞阳性率高于CSF常规检查炎性细胞阳性率(P=0.02),抗NMDAR脑炎患者CSF细胞学的炎性反应程度与患者入院时的改良Rankin评分(mRS)呈正相关(r=0.23,P<0.01)。结论本组AE患者CSF细胞学检查多表现为淋巴细胞炎性反应,抗NMDAR脑炎患者的CSF炎性反应阳性率最高,炎性反应程度最重。与CSF常规检查相比,CSF细胞学能够更敏感地发现AE的炎性反应,可作为诊断AE及评估疾病严重程度的重要方法。