Laryngospasm as an uncommon presentation in a patient with anti-N-methyl-D-aspartate receptor encephalitis:A case report

BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a rare autoimmune disorder.The symptoms of anti-NMDAR encephalitis include behavioral problems,speech problems,psychosis,seizures,and memory deficits,among others.However,laryngospasm is rare.We present the case of a patient with anti-NMDAR antibodies and severe laryngospasms.CASE SUMMARY The patient was a 15-year-old female with normal psychomotor development.She was initially admitted to our neurological intensive care unit with seizures.She received anti-epilepsy treatment,and the seizures disappeared.However,2 wk later,she developed behavioral problems and speech impairment.Then,she developed severe laryngospasms,which were treated with intubation and a tracheotomy.Antibodies against the NMDAR were detected in the patient’s cerebrospinal fluid.Therefore,she was diagnosed with anti-NMDAR encephalitis.In addition,she received intravenously administered immunoglobulins,and methylprednisolone was administered.The patient’s symptoms gradually improved,and she was discharged from our hospital.Approximately 9 mo later,the patient could speak sentences,walk independently,and carry out activities of daily living independently.Through our case report,we highlighted laryngospasm as an uncommon presentation in patients with anti-NMDAR encephalitis.CONCLUSION Laryngospasm may be an uncommon clinical manifestation of anti-NMDAR encephalitis.

Ovarian teratoma related anti-N-methyl-D-aspartate receptor encephalitis:A case series and review of the literature

BACKGROUND Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is a rare but important complication of ovarian teratoma.Between July 2012 and December 2019,six patients with ovarian teratoma-associated anti-NMDAR encephalitis were enrolled in our hospital and their clinical characteristics,treatment,and follow-up were reviewed.We also conducted a systematic literature review of ovarian teratoma related anti-NMDAR encephalitis reports between January 2014 and December 2019.AIM To better understand anti-NMDAR encephalitis through literature review and patients enrolled in our hospital.METHODS The six patients enrolled in the study were those diagnosed with anti-NMDAR encephalitis.Their history,clinical manifestations,and medications were recorded and optimum treatment provided in addition to maintaining a record of the follow-ups.In addition,we also extensively surveyed the literature and provide summarized data from 155 published cases of anti-NMDAR encephalitis from 130 case reports.PubMed and Scopus were the sources of these publications and the time period covered was 6 years ranging from January 2014 through December 2019.RESULTS The six patients enrolled for this study presented with typical symptoms resulting in a diagnosis of ovarian teratoma induced anti-NMDAR encephalitis.Appropriate interventions led to a positive outcome in all the patients,with five of six patients reporting full recovery and the sixth patient recovering with a few deficits.No death was recorded.The literature survey comprising of 155 patients cases across 130 case reports of anti-NMDAR encephalitis clearly indicated an upward trend in the reports/diagnosis in China,particularly in the surveyed time from 2014 through 2019.The majority of patients(150/155)underwent surgical intervention resulting in positive outcome.No treatment intervention was mentioned for one case while the four patients who were not surgically operated succumbed to the disease.CONCLUSION Suspected anti-NMDAR encephalitis should be quickly evaluated for anti-NMDAR antibodies since early diagnosis is important.In case of a tumor,its earliest and complete removal is recommended.Finally,early use of corticosteroids and IgG-depleting strategies(intravenous immunoglobulin or plasma exchange)may improve outcome.

Overlapping syndrome of recurrent anti-N-methyl-D-aspartate receptor encephalitis and anti-myelin oligodendrocyte glycoprotein demyelinating diseases:A case report

BACKGROUND Anti-N-methyl-D-aspartate receptor encephalitis(NMDARe)is capable of presenting a relapsing course and coexisting with myelin oligodendrocyte glycoprotein antibody disease,whereas it has been relatively rare.We describe a man with no history of tumor who successively developed anti-NMDARe and anti-myelin oligodendrocyte glycoprotein antibody disease.CASE SUMMARY A 29-year-old man was initially admitted with headache,fever,intermittent abnormal behavior,decreased intelligence,limb twitching and loss of consciousness on July 16,2018.On admission,examination reported no abnormality.During his presentation,he experienced aggravated symptoms,and the reexamination of cranial magnetic resonance imaging(MRI)indicated punctate abnormal signals in the left parietal lobe.External examination of cerebrospinal fluid and serum results revealed serum NMDAR antibody(Ab)(-),cerebrospinal fluid NMDAR-Ab(+)1:10 and Epstein-Barr virus capsid antigen antibody Ig G(+).Due to the imaging findings,anti-NMDARe was our primary consideration.The patient was treated with methylprednisolone and gamma globulin pulse therapy,mannitol injection dehydration to reduce intracranial pressure,sodium valproate sustained-release tablets for anti-epilepsy and olanzapine and risperidone to mitigate psychiatric symptoms.The patient was admitted to the hospital for the second time for“abnormal mental behavior and increased limb movements”on December 14,2018.Re-examination of electroencephalography and cranial MRI showed no abnormality.The results of autoimmune encephalitis antibody revealed that serum NMDAR-Ab was weakly positive and cerebrospinal fluid NMDAR-Ab was positive.Considering comprehensive recurrent anti-NMDARe,the patient was treated with propylene-hormone pulse combined with immunosuppressive agents(mycophenolate mofetil),and the symptoms were relieved.The patient was admitted for“hoarseness and double vision”for the third time on August 23,2019.Re-examination of cranial MRI showed abnormal signals in the medulla oblongata and right frontal lobe,and synoptophore examination indicated concomitant esotropia.The patient’s visual acuity further decreased,and the reexamination of cranial MRI+enhancement reported multiple scattered speckled and patchy abnormal signals in the medulla oblongata,left pons arm,left cerebellum and right midbrain,thalamus.The patient was diagnosed with an accompanying demyelinating disease.Serum antimyelin oligodendrocyte glycoprotein 1:10 and NMDAR antibody 1:10 were both positive.The patient was diagnosed with myelin oligodendrocyte glycoprotein antibody-related inflammatory demyelinating disease of the central nervous system complicated with anti-NMDARe overlap syndrome.The patient was successfully treated with methylprednisolone,gamma globulin pulse therapy and rituximab treatment.The patient remained asymptomatic and follow-up MRI scan 6 mo later showed complete removal of the lesion.CONCLUSION We emphasize the rarity of this antibody combination and suggest that these patients may require longer follow-up due to the risk of recurrence of two autoimmune disorders.

Four-year-old anti-N-methyl-D-aspartate receptor encephalitis patient with ovarian teratoma: A case report

BACKGROUND A population-based comparative study in United States shows that the prevalence and incidence of autoimmune encephalitis are comparable to those of infectious encephalitis and its detection is increasing over time.Some patients are complicated with ovarian teratoma.The younger the patient is,the less likely a tumor will be present.CASE SUMMARY This case report describes the successful treatment of anti-N-methyl-D-aspartatereceptor(NMDAR)encephalitis by early laparoscopic ovarian cystectomy and immunotherapy in a 4-year-old female child.And to the best of our knowledge,this detailed case report describes the youngest patient to date with anti-NMDAR encephalitis who underwent laparoscopic ovarian cystectomy.CONCLUSION Although the younger the patient is,the less likely a tumor will be detected,we still emphasize that all patients with suspected or confirmed anti-NMDAR encephalitis should be screened for ovarian tumors if possible.Prompt initiation of immunotherapy and tumor removal are crucial for good outcomes.

Paroxysmal speech disorder as the initial symptom in a young adult with anti-N-methyl-D-aspartate receptor encephalitis: A case report

BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a treatable but frequently misdiagnosed autoimmune disease.Speech dysfunction,as one of the common manifestations of anti-NMDAR encephalitis,is usually reported as a symptom secondary to psychiatric symptoms or seizures rather than the initial symptom in a paroxysmal form.We report a case of anti-NMDAR encephalitis with paroxysmal speech disorder as a rare initial manifestation,and hope that it will contribute to the literature.CASE SUMMARY A 39-year-old man with anti-NMDAR encephalitis initially presented with paroxysmal nonfluent aphasia and was misdiagnosed with a transient ischemic attack and cerebral infarction successively.The patient subsequently presented with seizures,but no abnormalities were found on brain magnetic resonance imaging or electroencephalogram.Cerebrospinal fluid(CSF)analysis revealed mild pleocytosis and increased protein levels.Anti-NMDAR antibodies in serum and CSF were detected for a conclusive diagnosis.After immunotherapy,the patient made a full recovery.CONCLUSION This case suggests that paroxysmal speech disorder may be the presenting symptom of anti-NMDAR encephalitis in a young patient.

Anti-N-methyl-D-aspartate receptor encephalitis that aggravates after acinetobacter baumannii pneumonia:A case report

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.

Anesthetic Management of Patients with Anti-N-methyl-D-aspartate Receptor Encephalitis:A Report of Two Cases

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.

Intravenous immunoglobulin accompanied with high-dose methylprednisolone therapy for 17 children with anti-N-methyl-D-aspartate receptor encephalitis:Clinic and nursing

Objective:An increasing number of pediatric patients are being diagnosed with anti-N-methyl-Daspartate receptor(NMDAR)encephalitis,whose treatment requires immunotherapy through nursing interventions.This study aimed to analyze the clinical features and long-term prognosis of pediatric anti-NMDAR encephalitis and to gather nursing experiences of immunotherapy.Methods:Seventeen children diagnosed with anti-NMDAR encephalitis were admitted to the pediatric department.They were subjected to a therapy of intravenous immunoglobulin(IVIG)accompanied with high-dose methylprednisolone(HDMP).Multidisciplinary cooperation and intensive care were used to manage them.The effects of nursing intervention and therapy were repeatedly assessed and analyzed throughout the course of treatment and recovery.Results:None of the patients manifested adverse drug reaction(ADR)during IVIG administration.At the first administration of HDMP,ADRs were promptly and efficiently treated in four patients(24%;i.e.,one case each of hyperglycosemia,hypertension,aggravated symptoms,and gastrointestinal bleed).Two patients underwent rehabilitation,and six patients received hyperbaric oxygenation during hospitalization.Nine patients with indwelling gastric tubes experienced four times of unplanned extubation.Hospital stay ranged from 11 days to 59 days,with the mean duration of 26 days.Discharge evaluation revealed that 16 patients who scored 0e2 on the modified Rankin scale presented obvious remission,and one patient who had a mRS score of 4 exhibited less improvement.The mRS scores of hospitalization,discharge,and six-month follow-up displayed statistically significant differences.Conclusions:Nursing interventions of immunotherapy ensures the security of IVIG administration.Multidisciplinary cooperation promotes remission.Our findings can serve as reference for healthcare teams.

Anti-N-methyl-D-aspartate-receptor antibody encephalitis combined with syphilis:A case report

BACKGROUND Anti-N-methyl-D-aspartate-receptor(NMDAR)encephalitis is a common type of autoimmune encephalitis characterized by complex clinical signs and variable imaging manifestations.The pathogenesis of the disease is unclear.Syphilis is an infectious disease caused by Treponema pallidum that can invade the nervous and immune systems and cause systemic symptoms.There are few reports of anti-NMDAR encephalitis with syphilis,and the association between them is unknown;both diseases are related to immune system damage.We report a case of anti-NMDAR encephalitis with syphilis.CASE SUMMARY A 32-year-old man was admitted to our hospital with complaints of cognitive decline,diplopia,and walking instability during the previous 6 mo.He developed dysarthria,difficulty swallowing,and involuntary shaking of his head,neck,and limbs during the month prior to presentation.Cranial magnetic resonance imaging showed symmetrical abnormal signals in the pons,midbrain,and bilateral basal ganglia,and inflammatory demyelination was considered.The diagnosis of syphilis was confirmed based on the syphilis diagnosis test and the syphilis rapid test.He was given anti-syphilis treatment,but the above symptoms gradually worsened.Anti-NMDAR antibody was positive in cerebrospinal fluid but was negative in serum.Due to the cerebrospinal fluid findings,anti-NMDAR encephalitis was a consideration.According to the patient’s weight,he was treated with intravenous methylprednisolone 1 g QD for 5 d,with the dose gradually decreased for 6 mo,and immunoglobulin 25 g QD for 5 d;his symptoms improved after treatment.CONCLUSION This case shows that anti-NMDAR encephalitis may be combined with syphilis,which should be recognized to avoid misdiagnosis and treatment delay.

Anti-N-methyl-D-aspartate receptor encephalitis in a 17-year-old female patient with 3 years of follow-up

To the Editor:Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is a potentially lethal autoimmune disease characterized by prominent psychiatric symptoms and seizures.It usually occurs in young female patients with ovarian teratomas.[1] Here,we describe a severe case of anti-NMDAR encephalitis.The patient was originally misdiagnosed as psychosis and did not improve within the first 4 weeks of first-line immunotherapy.Although she did not continue to receive second-line immunotherapy,the patient still recovered well and had no recurrence or tumor observed during 3 years of follow-up.

Anti N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis with Frustrated Diagnosis Course: A Case Report

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a rare disease with uncertain etiology and pathogenesis that affects young women. Its diagnosis can be delayed because of the nonspecific neuropsychiatric symptoms in the foreground. This article describes the details of a recent complicated case of a patient with this condition which is related to an ovarian teratoma. Correct diagnostic and prompt treatment of anti-NMDA receptor encephalitis remains a serious clinical challenge due to its unspecific manifestations and varying response to treatments. The information will be of interest to clinicians working with encephalitis patients.

Anti-N-methyl-D-aspartate receptor encephalitis in China

N-methyl-D-aspartate receptors(NMDARs)are mainly distributed in the central nervous system,and play important roles in the mechanisms of learning and memory.A newly discovered disease caused by autoantibody to NMDAR has been described,and is called anti-NMDAR encephalitis.Patients with this disease often suffer from mental disorders,seizures and other encephalitis-like symptoms.Accumulated data suggests that the severity of the disease makes early diagnosis very important.Accurately detecting the autoantibody to NMDAR is considered to be the gist of diagnosis.Good prognosis is predicted in most patients,when treated properly.Immunotherapy is preferred in most cases.In China,this disease has been reported only for a few years,but sporadic case reports are also helpful for profiling.

In silico insight into Amurensinine - an N-Methyl-D-Aspartate receptor antagonist

BACKGROUND Some isopavines can exhibit important biological activity in the treatment of neurological disorders since it is considered an antagonist of the specific Nmethyl-D-Aspartate(NMDA)receptor.Amurensinine is an isopavine which still has few studies.In view of the potential of isopavines as NMDA receptor antagonists,theoretical studies using bioinformatics were carried out in order to investigate whether Amurensinine binds to the NMDA receptor and to analyze the receptor/Ligand complex.This data can contribute to understanding of the onset of neurological diseases and contribute to the planning of drugs for the treatment of neurological diseases involving the NMDA receptor.AIM To investigate the interaction of the antagonist Amurensinine on the GluN1A/GluN2B isoform of the NMDA receptor using bioinformatics.METHODS The three-dimen-sional structure of the GluN1A/GluN2B NMDA receptor was selected from the Protein Data Bank(PDB)-PDB:4PE5,and the three-dimensional structure of Amurensinine(ligand)was designed and optimized using ACD/SchemsketchTM software.Prediction of the protonation state of Amurensinine at physiological pH was performed using MarvinSketch software(ChemAxon).Protonated and non-protonated Amurensin were prepared using AutoDock Tools 4 software and simulations were performed using Autodock Vina v.1.2.0.The receptor/Ligand complexes were analyzed using PyMol(Schrödinger,Inc)and BIOVIA Discovery Studio(Dassault Systemes)software.To evaluate the NMDA receptor/Amurensinine complex and validate the molecular docking,simulations using NMDA receptor and Ifenprodil antagonist were performed under the same conditions.Ifenprodil was also designed,optimized and protonated,under the same conditions as Amurensinine.RESULTS Molecular docking simulations showed that both non-protonated and protonated Amurensinine bind to the amino terminal domain(ATD)domain of the GluN1A/GluN2B NMDA receptor with significant affinity energy,-7.9 Kcal/mol and-8.1 Kcal/mol,respectively.The NMDA receptor/non-protonated Amurensinine complex was stabilized by 15 bonds,while the NMDA receptor/protonated Amurensinine complex was stabilized by less than half,6 bonds.Despite the difference in the number of bonds,the variation in bond length and the average bond length values are similar in both complexes.The complex formed by the NMDA receptor and Ifenprodil showed an affinity energy of-8.2 Kcal/mol,a value very close to that obtained for the NMDA receptor/Amurensinine complex.Molecular docking between Ifenprodil and the GluN1A/GluN2B NMDA receptor demonstrated that this antagonist interacts with the ATD of the receptor,which validates the simulations performed with Amurensinine.CONCLUSION Amurensinine binds to the NMDA receptor on ATD,similar to Ifenprodil,and the affinity energy is closer.These data suggest that Amurensinine could behave as a receptor inhibitor,indicating that this compound may have a potential biological application,which should be evaluated by in vitro and preclinical assays.

N-methyl-D-aspartate receptor subunit 1 regulates neurogenesis in the hippocampal dentate gyrus of schizophrenia-like mice

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.

Propofol effectively inhibits lithium-pilocarpine-induced status epilepticus in rats via downregulation of N-methyl-D-aspartate receptor 2B subunit expression

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.

Influences of levodopa on expression of N-methyl-D-aspartate receptor-1-subunit in the visual cortex of monocular deprivation rats

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.

Four kinds of antibody positive paraneoplastic limbic encephalitis: A rare case report

BACKGROUND It is not uncommon to develop autoimmune encephalitis and paraneoplastic neurological syndromes(PNS).4 kinds of antibody-positive autoimmune paraneoplastic limbic encephalitis(PLE)have not been reported.CASE SUMMARY PNS are distant effects of cancer on the nervous system,rather than syndromes in which cancer directly invades and metastasizes to the nerves and/or muscle tissues.If the limbic lobe system of the brain is involved,this will result in PLE.The detection of patients with PNS is challenging since tumors that cause paraneoplastic neurologic disorders are often asymptomatic,obscure,and thus easily misdiagnosed or missed.Currently,single-or double-antibody-positive paraneoplastic marginal encephalitis has been reported.However,no cases of three or more-antibody-positive cases have been reported.Here,we report a case of PLE that is anti-collapsing response-mediator protein-5,anti-neuronal nuclear antibody-type 1,anti-aminobutyric acid B receptor,and anti-glutamate deglutase positive,and address relevant literature to improve our understanding of the disease.CONCLUSION This article reports on the management of a case of PLE with four positive antibodies,a review of the literature,in order to raise awareness among clinicians.

Clinical features of AMPAR2 antibody-positive autoimmune encephalitis with gastrointestinal hemorrhage: a case report

Objective:To describe the clinical fea-tures of autoimmune encephalitis complicated with gas-trointestinal hemorrhage.Methods:The clinical data of one patient whose initial symptom was mental abnor-mality were collected and the related examinations,such as cerebrospinal fluid and magnetic resonance imaging (MRI),were improved.Results: Cerebrospinal fluid ex-amination found that anti-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)2 antibody was strongly positive,although the patient had repeated gastrointestinal hemorrhage but,after hormone combined with immunoglobulin treatment,the symptoms gradual-ly improved.Conclusion:Mental disorders are not all psychosis,and autoimmune encephalitis should not be ignored.It is very important to perform anti-AMPAR encephalitis antibody test;accurate diagnosis and timely treatment can improve the prognosis.

Changes in synaptic and extrasynaptic N-methyl-D-aspartate receptor-mediated currents at early-stage epileptogenesis in adult mice

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.

Kappa opioid receptor antagonist and N-methyl-D-aspartate receptor antagonist affect dynorphin-induced spinal cord electrophysiologic impairment

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.