A case report of anti-NMDAR encephalitis complicated with acute peripheral nerve damage / 中国综合临床

N-methyl-D-aspartate receptor (NMDAR) encephalitis in combination with acute peripheral nerve damage is rare. A young female patient with anti-NMDAR encephalitis was admitted to Qianfoshan Hospital in Shandong Province on October 23, 2022. The main manifestations were abnormal mental behavior, consciousness disorders, and flaccid paralysis. Electromyography indicated axonal damage to the upper and lower extremities. Patient was in critical condition and admitted to the ICU with tracheal intubation for central hypoventilation. A combination of critical polyneuropathy was considered. The prognosis was good after hormone shock, immunosuppressive therapy, surgical therapy, anti-infection, respiratory support and symptomatic support. The diagnosis of anti-NMDAR encephalitis with acute peripheral nerve damage is difficult. Immune factors need to be considered and paraneoplastic syndrome should be differentially diagnosed.

A novel NMDA receptor modulator:antidepressant ef-fect and mechanism of GW043 / 中国药理学与毒理学杂志

OBJECTIVE The N-methyl-D-aspartate(NMDA)receptor has been shown to be strongly associ-ated with rapid antidepressant effects.GW043 is a com-pound with a novel structure that we designed and syn-thesized to act on the NMDA receptor(NMDAR).METH-ODS In this study,we first confirmed the target of GW043 using a receptor binding assay.We observed the effect of GW043 on NMDAR currents in vivo and in vitro assays using a membrane clamp technique with a view to characterizing the function of GW043.We investi-gated the antidepressant effect of GW043 in rodent behavioral models such as FST,TST and CUMS.Fur-thermore,we explored the mechanism of GW043 onset using Western blotting,BrdU staining,Golgi staining and electrophysiological techniques.RESULTS GW043 interacts with high affinity only at the NMDAR.Electro-physiological studies have indicated that GW043 is a par-tial agonist of NMDAR.Meanwhile,behavioral experi-ments were conducted to confirm the antidepressant effect of GW043 in rodents.The mechanism study found that GW043 regulate synaptic plasticity through LTP and BDNF/mTOR pathways and increase the number of new-born neurons to cause antidepressant effects.GW043,a partial agonist of NMDAR,reversed depression-like behav-ior in rats by modulating synaptic plasticity,suggesting an antidepressant effect.CONCLUSION The results suggest that GW043 is a partial agonist of NMDA recep-tors and has significant antidepressant effects.

Prodromes and biological markers in schizophrenia: Importance for the dopamine, glutamate, and neurodevelopmental hypothesis / Pródromos e indicadores biológicos en la esquizofrenia: Importancia para la hipótesis dopaminérgica, glutamatérgica y del neurodesarrollo

Abstract Background Since schizophrenia is a multifactorial mental illness, a basic understanding of its etiological components improves its understanding, diagnosis, and the selection of therapeutic targets. Objective To identify the prodromes and biological markers in schizophrenic or ultra-high risk (UHR) patients and elucidate their specificity. Method Narrative review of relevant sources in English and Spanish in the Medline-PubMed database on minor physical abnormalities, cognitive abnormalities, neuroanatomical, and synaptic and cell changes present in schizophrenic patients and/or subjects with a high risk of developing schizophrenia Results Patients with SZ and, to a lesser extent, UHR subjects present phenotypic and behavioral manifestations that correlate with underlying cell processes. The study of the latter makes it possible to characterize diagnostic biomarkers. At present, its clinical application is limited by factors such as poorly understood pathophysiology, lack of study models, homology with other psychiatric disorders, and the dearth of clinical trials conducted. Discussion and conclusion Schizophrenia is the final manifestation of damage to prenatal and post-natal neurodevelopment and is reflected during the prodromal stage in early biological markers with clinical relevance. It is necessary to establish new study models that will increase knowledge to offer specific biomarkers for use in early clinical diagnosis.

Resumen Antecedentes La esquizofrenia es una enfermedad mental multifactorial. Una comprensión básica de sus componentes etiológicos mejora su entendimiento, su diagnóstico y la selección de posibles blancos terapéuticos. Objetivo Reportar los pródromos e indicadores biológicos en pacientes esquizofrénicos o de ultra-alto riesgo (UHR) y dilucidar su especificidad. Método Revisión narrativa de fuentes relevantes en inglés y español en la base de datos Medline-PubMed sobre las anomalías física menores, anomalías cognitivas, cambios neuroanatómicos, sinápticos y celulares presentes en pacientes esquizofrénicos y/o en sujetos de UHR. Resultados Los pacientes con EZ y, de manera menos predominante, los sujetos de UHR presentan manifestaciones fenotípicas y conductuales que se correlacionan con los procesos celulares subyacentes. El estudio de éstos permite caracterizar diferentes biomarcadores diagnósticos. En la actualidad, su aplicación en la clínica es limitada por distintos factores como son la fisiopatología poco comprendida, la falta de modelos de estudio, la homología con otros trastornos psiquiátricos y los escasos ensayos clínicos realizados. Discusión y conclusión La esquizofrenia es la manifestación final de daños en el neurodesarrollo prenatal y post-natal, y se refleja durante la etapa prodrómica en indicadores biológicos tempranos con relevancia clínica. Se requiere establecer nuevos modelos de estudio que permitan ampliar el conocimiento para ofrecer biomarcadores específicos para ser usados en el diagnóstico clínico temprano.

Does mismatch negativity have utility for NMDA receptor drug development in depression?

Rapid antidepressant effects associated with ketamine have shifted the landscape for the development of therapeutics to treat major depressive disorder (MDD) from a monoaminergic to glutamatergic model. Treatment with ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, may be effective, but has many non-glutamatergic targets, and clinical and logistical problems are potential challenges. These factors underscore the importance of manipulations of binding mechanics to produce antidepressant effects without concomitant clinical side effects. This will require identification of efficient biomarkers to monitor target engagement. The mismatch negativity (MMN) is a widely used electrophysiological signature linked to the activity of NMDA receptors (NMDAR) in humans and animals and validated in pre-clinical and clinical studies of ketamine. In this review, we explore the flexibility of the MMN and its capabilities for reliable use in drug development for NMDAR antagonists in MDD. We supplement this with findings from our own research with three distinct NMDAR antagonists. The research described illustrates that there are important distinctions between the mechanisms of NMDAR antagonism, which are further crystallized when considering the paradigm used to study the MMN. We conclude that the lack of standardized methodology currently prevents MMN from being ready for common use in drug discovery. Clinical trial registration: This manuscript describes data collected from the following National Institutes of Health (NIH) and Veterans Affairs (VA) studies: AV-101, NCT03583554; lanicemine, NCT03166501; ketamine, NCT02556606.

Factors affecting the clinical outcome of pediatric Anti- N-Methyl-Daspartate receptor encephalitis, a single center study

BACKGROUND@#Anti-N-Methyl-D-Aspartate receptor (anti-NMDAR) Encephalitis is the most common type of autoimmune encephalitis that affects children, adolescents and young adults. Since its discovery in 2007, there is still a paucity of data on the disease and factors affecting its outcome.@*OBJECTIVES@#To describe the clinical characteristics of children and adolescents with anti-NMDAR encephalitis and to analyze factors that may affect its outcome.@*METHODS@#Forty-three patient records of diagnosed anti-NMDAR Encephalitis were included. The outcome was evaluated using the modified Rankin Scale (mRS), and Clinical Assessment Scale for autoimmune Encephalitis (CASE). @*RESULTS@#Ages ranged from 2 years to 18 years old, majority in the 12-18 years age range. Sixty percent were female. First line treatment using immunotherapy was given to all patients: 37% as monotherapy and 84% combination therapy (MPT only 23%, IVIg only 4%, MPT + IVIg or TPE 21-26%, and MPT + IVIg + TPE 16%). Clinical outcomes on discharge and on follow-up were assessed using the mRS and CASE. On discharge the proportion of the patients who had mild impairment (mRS<2, CASE<9) was more than 50%. On median duration follow-up of 31 weeks (range 24-40 weeks), 96.8% had significant improvement (mRS<2, CASE<9). Among the possible factors that were assessed to affect outcome, only severity of the illness at the start of the treatment influenced clinical outcome.@*CONCLUSION@#Early diagnosis and initiation of treatment before the progression of the disease will promote faster recovery and more optimal clinical outcome. CASE may be used as an additional tool in assessing response to treatment.

A novel cell tool for α2δ-1-NMDAR target-based analgesic drug discovery / 生物工程学报

The α2δ-1 protein coded by Cacna2d1 is dramatically up-regulated in dorsal root ganglion (DRG) neurons and spinal dorsal horn following sensory nerve injury in various animal models of neuropathic pain. Cacna2d1 overexpression potentiates presynaptic and postsynaptic NMDAR activity of spinal dorsal horn neurons to cause pain hypersensitivity. The α2δ-1-NMDAR interaction promotes surface trafficking and synaptic targeting of NMDARs in neuropathic pain caused by chemotherapeutic agents and peripheral nerve injury, as well as in other pathological conditions such as in the paraventricular nucleus (PVN) with neurogenic hypertension and in the brain with ischemic stroke. The lentiviral transfection method was used to construct a human embryonic kidney HEK293T cell line that could stably express α2δ-1-NMDAR complex. A stably transfected cell line was observed by florescence microscope, and identified by RT-qPCR and Western blotting. The results showed that the HEK293T cell line was successfully transfected and the genes could be stably expressed. Subsequently, the transfected cell line was successfully developed into a target drug screening system using patch clamp techniques. It provides a promising cell model for further research on the interaction mechanism of α2δ-1-NMDAR complex and drug screening for chronic pain and related diseases with low side effects.

Plasma prevalence of anti-N-methyl-d-aspartate receptor IgG antibodies in early stages of psychosis / Prevalência plasmática de anticorpos IgG antirreceptor N-metil-d-aspartato nos estágios iniciais de psicose

Abstract We investigated the feasibility of including plasma anti-NMDAR antibody screening in the assessment of first-episode psychosis patients in an early intervention programme in the Southern hemisphere. Anti-NMDAR IgG antibodies were assessed by ELISA in 166 patients (64.0% men), 166 matched population-based controls and 76 patients' siblings (30.3% men). Fisher's exact test and ANOVA were performed. Positive anti-NMDAR antibody patients were more often observed in bipolar disorder (10.0%) than schizophrenia (2.4%) or psychotic depression (3.1%), although no significant differences were observed. Our results are not conclusive regarding the inclusion of plasma anti-NMDAR IgG antibodies in differential diagnostic protocols for psychosis.

Resumo Nós investigamos a viabilidade de incluir a pesquisa de anticorpos anti-NMDAR na avaliação de pacientes em primeiro episódio psicótico em um programa de intervenção precoce no Hemisfério Sul. Anticorpos IgG anti-NMDAR foram avaliados por ELISA em 166 pacientes (64,0% homens), 166 controles de base populacional pareados e 76 irmãos (30,3% homens). Foram realizados teste exato de Fisher e ANOVA. Os anticorpos anti-NMDAR positivos foram mais observados no transtorno afetivo bipolar (10,0%) do que na esquizofrenia (2,4%) ou depressão psicótica (3,1%), embora não tenham sido observadas diferenças significativas. Nossos resultados não são conclusivos quanto à inclusão de anticorpos IgG anti-NMDAR no plasma em protocolos de diagnósticos diferenciais para psicose.

The Technique of Intravenous Ketamine Infusion on PostOperative Hyperalgesia in Gluteal Sarcoma

@#Post-Operative Hyperalgesia (POH) is an uncommon painful condition suffered after surgery. It is poorly identified and usually needs a large dose of strong opioids administration to attenuate pain. Primarily POH originated from the activation of N-Methyl-DE Aspartate Receptor (NMDAR) located at the spinal cord. Hence NMDAR antagonist (ketamine) may inhibit this pain mechanism leading to desirable post-operative pain relief. We presented a case report on how to recognize POH, initiated ketamine infusion, and its limitation. We found ketamine therapy reduced opioid requirements and drastically improve patient daily bed activities.

Anti-N-methyl-D-aspartate receptor (NMDAR) Encephalitis in Malaysia: A Review Article

@#N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis is recognized as an autoimmune encephalitis, which is due to autoantibodies against synaptic NMDAR. This disorder affects individuals aged 23 months to 76 years and has a wide range of presentations. In Malaysia, more than 20 cases have been reported. Timely diagnosis and definitive immunotherapy are vital in optimizing functional recovery and prognosis. However, early diagnosis of the condition is often missed due to low awareness among clinicians in Malaysia. This article gathered the medical literature from Malaysia and highlights the aetio-pathophysiology, clinical presentation and management of the disease.

Mechanism of Chuanxiong Rhizoma intervention on central sensitization of Panx1-Src-NMDAR-2B signaling pathway in neuropathic pain model rats / 中国中药杂志

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1β(IL-1β), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.

Ictal Iaryngospasm as a main feature in a patient with anti-NMDA receptor encephalitis / 中国综合临床

Anti-N-methyl-aspartate receptor encephalitis (anti-NMDARE) is a rare autoimmune panencephalitis. We report the case of a patient with anti-NMDARE with severe ictal laryngospasm. A 17-year old boy was referred to our neurological intensive care unit for refractory behavioural symptoms and cognitive decline. Brain magnetic resonance imaging was normal. Screening for antineuronal antibodies showed positive results for anti-NMDA in serum and cerebrospinal fluid,which confirmed the diagnosis of anti-NMDARE. During his admission,he developed severe ictal laryngospasm resulting in intubation, tracheostomy, and repeated courses of intravenous immunoglobulin and methylprednisolone. The patient then made an uneventful recovery and was discharged to outpatient follow-up. Our report intends to raise awareness that patients with anti-NMDARE may manifest fatal ictal laryngospasm,requiring urgent and aggressive management.

Encefalitis límbica: clínica, patogenia y problemas diagnósticos / Limbic encephalitis: clinic, pathogenesis and diagnostic problems

La encefalitis límbica es una enfermedad infrecuente y potencialmente grave, que puede o no ser paraneoplásica y se caracteriza por déficit de la memoria reciente, alteraciones psiquiátricas y convulsiones. De origen autoinmunitario, está asociada a anticuerpos séricos e intratecales contra antígenos neuronales intracelulares y de superficie, con especial afectación de zonas límbicas. En este artículo se revisan aspectos históricos y epidemiológicos, patogenia, síndromes más frecuentes y mejor delimitados, histopatología y estudios complementarios. Se repasan también las dificultades del diagnóstico diferencial y la necesidad de descartar siempre un tumor subyacente. La detección de autoanticuerpos neuronales es importante para el diagnóstico, la planificación terapéutica y el pronóstico. La inmunoterapia y, si corresponde, el tratamiento de la neoplasia son cruciales para lograr una recuperación neurológica sustancial. La encefalitis límbica es una entidad probablemente subdiagnosticada, con un pronóstico más favorable si se trata de forma temprana. El actual conocimiento de su patogenia puede además aportar claridad para la mejor comprensión de otros síndromes neurológicos y psiquiátricos que puedan compartir mecanismos autoinmunitarios, como algunos trastornos psicóticos y epilepsias farmacorresistentes. (AU)

Limbic encephalitis is a rare and potentially serious disease, which may or may not be paraneoplastic and is characterized by recent memory deficits, psychiatric disturbances and seizures. Of autoimmune origin, it is associated with serum and intrathecal antibodies against intracellular and surface neuronal antigens, with special involvement of limbic areas. This article reviews historical and epidemiological aspects, pathogenesis, more frequent and better defined syndromes, histopathology and complementary studies. The difficulties of differential diagnosis and the need to always rule out an underlying tumor are also reviewed. Detection of neuronal autoantibodies is important for diagnosis, therapeutic planning and prognosis. Immunotherapy and, if appropriate, neoplasm treatment, are crucial to achieve substantial neurological recovery. Limbic encephalitis is probably an underdiagnosed entity, with a more favorable prognosis if treated early. The current knowledge of its pathogenesis may also provide clarity for a better understanding of other neurological and psychiatric syndromes that may share autoimmune mechanisms, such as some psychotic disorders and drug-resistant epilepsies. (AU)

Anti NMDA receptor encephalitis: a potentially treatable encephalitis

Anti NMDA receptor encephalitis is autoimmune encephalitis where antibodies are directed against NMDA receptor subunit. It represents a new category of immune-mediated disorder that is often paraneoplastic, presenting with neuropsychiatric symptoms, which is treatable and can be diagnosed serologically affecting both children and adults. Patient can have variable clinical presentation ranging from prodromal illness, neuropsychiatric symptoms, seizures, autonomic instability, hyperkinesias, catatonia, hypoventilation and with or without an associated teratoma. A positive serum or CSF sample screening for antibodies to the NMDA receptor subunit is confirmative. Supportive findings include CSF study, EEG and MRI Brain. The first-line therapies includes IVIG, corticosteroids or plasma exchange. Second line immunotherapy is rituximab or cyclophosphamide or both. Given the high mortality rate (up to 25%), the likelihood of presentation across the age range and the potential for treatment, a high index of suspicion is warranted by clinicians. Authors report a case of a 5 year old child with anti NMDA receptor encephalitis who responded well to IVIG therapy.

Neuroprotective effects of salidroside on GSK-3β in rats with cerebral ischemia/reperfusion / 中国药理学通报

Aim To study the effects of salidroside on the caspase-9, GSK-30, NMDAR1, GluR2 in MCAO ratsand to further explore the mechanism of neuroprotection of salidroside. Methods For the first part, 36 healthy male Sprague-Dawley rats were randomly divided into sham operation (Sham) group, model (MCAO) group, and salidroside (MCAO + Sal) group. Rats were administered salidroside, or vehicle, daily for 1 day, after middle cerebral artery occlusion (MCAO) 2 h and reperfusion 1 h. The protein expression of GSK-3β, NMDAR1, GluR2 and caspase-9 was detected by Western blot. For the second part, rats were randomly divided into Sham group, SB216763 + Shamgroup, MCAO group, SB216763 + MCAO group, MCAO + Sal group, and SB216763 + MCAO + Sal group. After 30 minutes of injection of GSK-3βinhibitor SB216763 or artificial cerebrospinal fluid into the lateral ventricle, the other groups were subjected to MCAO modeling except for the sham operation group. After the modeling, the administration group was given salidroside, and the material was taken after 1 day. The protein expression of GSK-3β, NMDAR1, GluR2 andcaspase-9 was detected by Western blot. Results Compared with MCAO group, salidroside could reduce the protein expression of cleaved caspase-9 protein in mitochondria and promote the expression of pGSK-3β, NMDAR1, GluR2 protein after 1 day salidroside treatment. And the treatment of salidroside and GSK-3β inhibitor did not show remarkable additive effects. Conclusions Salidroside has a neuroprotective effect on MCAO rats, mainly by promoting GSK-3β phosphorylation, thereby inhibiting caspase-9 and promoting protein expression of NMDAR1 and GluR2.

Effect of wrist-ankle acupuncture on the expression of glutamate and NMDA receptor of the spinal dorsal horn in rats with neuropathic pain / 针刺研究

OBJECTIVE: To observe the effect of wrist-ankle acupuncture (WA) stimulation at "R4"- "R5" - "R6" on the expression of glutamate (Glu) and phosphorylated protein NMDAR1(p-NMDAR1) of the spinal dorsal horn in spared nerve injury (SNI) rats, so as to explore its mechanism underlying improvement of SNI. METHODS: A total of 36 SD rats were randomly divi-ded into sham operation, model and WA groups, with 12 rats in each group. The SNI procedure comprised an axotomy and ligation of the tibial and common peroneal nerves leaving the sural nerve intact. Rats of the WA group were treated by acupuncture at "R4"-"R5"-"R6" points from the 5th day to the 14th day after modeling. The mechanical pain thresholds were measured before and 5, 10 and 14 d after SNI, respectively. The cold allodynia was dectected by Acetone solution dropped onto the lateral plantar surface of the paw. Glu content and p-NMDAR1 expression of spinal dorsal horn were detected by 1H-MRS, ELISA and immunohistochemistry Methods. RESULTS: Compared with the sham operation group, the mechanical pain threshold of the model group was significantly decreased (P<0.01), the duration of cold stimulation foot contraction was increased (P<0.01), and the Glu content and p-NMDAR1 expression in the spinal dorsal horn were significantly increased (P<0.05, P<0.01). After WA intervention, the mechanical pain threshold was significantly increased (P<0.01), the duration of cold stimulation was significantly shortened (P<0.01), and Glu content and p-NMDAR1 protein expression of spinal dorsal horn were decreased significantly (P<0.05, P<0.01) in the WA group compared with the model group. CONCLUSION: WA can reduce pain sensitivity in rats with neuropathic pain, possibly by inhibiting the expression of Glu and p-NMDAR1 in the spinal dorsal horn.

Encefalitis autoinmunes: Receptor anti-NMDA y nuevos inmunofenotipos / Autoimmune encephalitis. Anti-NMDA receptor and new immunophenotypes

Las encefalitis autoinmunes (EA) se definen como síndromes neurológicos de instalación subaguda de compromiso de conciencia, alteración de la memoria de trabajo y trastornos psiquiátricos frecuentemente asociados a movimientos anormales y crisis epilépticas y que se producen por la acción de anticuerpos anti neuronales específicos que se fijan a receptores de neurotransmisores o proteínas de membrana. El anticuerpo anti NMDAR es el que origina la mayoría de los casos de EA en niños y adultos jóvenes, seguido por el anticuerpo anti LGI1 de presentación en el adulto. Las EA han aumentado en la última década, en la que se ha descrito un gran número de nuevos anticuerpos que producen en su mayoría síndromes neurológicos que involucran al sistema nervioso central, con predominio de signología psiquiátrica, excepto en niños en los que predominan movimientos anormales, crisis epilépticas y compromiso de conciencia. Se asocian frecuentemente a tumores en el adulto pero en los niños esta asociación es más rara. Todas las EA responden a terapia inmunomoduladora aunque en diferente medida según el tipo de anticuerpo involucrado. Generalmente la evolución a la mejoría es lenta y puede completarse en meses o incluso en un año o más. En esta revisión se destaca los principales cuadros de EA relacionados con anticuerpos específicos mencionando también los inmunofenotipos descubiertos recientemente.

Autoimmune encephalitis (AE) is defined as neurological syndromes of subacute installation of compromise of consciousness, alteration of working memory and psychiatric disorders associated with abnormal movements and epileptic seizures and that are produced by the action of anti-neuronal antibodies. They bind to neurotransmitter receptors or membrane proteins. Antibody to NMDAR is the origin of the majority of cases of AD in children and young adults, followed by anti-LGI1 antibody for presentation in adults. The AE has increased in the last decade, with a large number of new agents described that produce mostly neurological syndromes that involve the central nervous system, with predominance of psychiatric signaling, except in children and the predominant abnormal movements, epileptic seizures and compromise of conscience. They are frequently associated with tumors in adults but in children this association is more infrecuent. All AEs respond to immunomodulatory therapy although in different measures depending on the type of antibody involved. In general, the evolution to improvement is slow and can be completed in months or even in one year or more. In this review, the main EA clinical pictures related to specific antibodies are highlighted, also mentioning recently discovered immunophenotypes.

Behavioral Abnormality along with NMDAR-related CREB Suppression in Rat Hippocampus after Shortwave Exposure / 生物医学与环境科学（英文）

OBJECTIVE@#To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms.@*METHODS@#One hundred Wistar rats were randomly divided into four groups (25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 mW/cm2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram (EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor (NMDAR) subunits (NR1, NR2A, and NR2B), cAMP responsive element-binding protein (CREB) and phosphorylated CREB (p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure.@*RESULTS@#The rats in the 10 and 30 mW/cm2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 mW/cm2 group had increased expressions of NR2A and NR2B and decreased levels of CREB and p-CREB.@*CONCLUSION@#Shortwave exposure (27 MHz, with an average power density of 10 and 30 mW/cm2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.

Application of N-methyl-aspartate receptor antibody level, brainstem auditory evoked potential and magnetic resonance imaging in the differential diagnosis of encephalitis in children / 中华实验和临床病毒学杂志

Objective@#To explore the clinical value of serum N-methyl-aspartate receptor (NMDAR) antibody level, brainstem auditory evoked potential (BAEP) and magnetic resonance imaging (MRI) in the differential diagnosis of viral encephalitis and anti-NMDAR encephalitis.@*Methods@#The clinical data of 68 children patients with encephalitis were retrospectively analyzed. The patients diagnosed with viral encephalitis were included in V group (n=52), and the patients diagnosed with anti-NMDAR encephalitis were included in N group (n=16). The clinical characteristics, serum NMDAR antibody level, and BAEP and MRI findings were compared between the two groups.@*Results@#The age, disease duration, abnormal behavior rate, sleep disorder rate and epileptic seizure rate in V group were significantly lower than those in N group [(6.62±1.20)Y/O vs.(8.46±1.85)Y/O, (3.53±0.71)d vs.(4.49±0.82)d, 30.77%(16/52)vs. 75.00%(12/16), 21.15%(11/52)vs. 62.50%(10/16), 26.92%(14/52)vs. 56.25%(9/16), t=4.681, t=4.560, χ2=9.882, χ2=7.958, χ2=4.701], while the abnormal rate of video EEG was significantly higher than that in N group [51.92(27/52)vs. 81.25%(13/16), χ2=4.345] (all P<0.05). There were no significant differences in gender, rates of prodromic infection symptoms, cognitive impairment, fever, headache, convulsion and incidence rate of meningeal irritation sign (P>0.05). The serum NMDAR antibody level in V group was significantly lower than that in N group [(3.40±0.69) ng/ml vs.(13.95±2.78) ng/ml t=25.319)] (P<0.05). There were no significant differences in the BAEP apparent involvement range and central auditory neurological damage between the two groups (P>0.05), but the peripheral auditory nerve damage and total BAEP abnormality rate in V group were significantly lower than those in N group [3.85%(4/104)vs. 21.88%(7/32), 6.73%(7/104)vs. 28.12%(9/32), 30.77%(16/52)vs. 62.50%(10/16), χ2=10.699, χ2=10.790, χ2=5.216] (all P<0.05). There were no significant differences in MRI signal intensity, lesion involvement range and total abnormal rate between the two groups (all P>0.05).@*Conclusions@#There were significant differences in serum NMDAR antibody level and BAEP test results among children patients with viral encephalitis or anti-NMDAR encephalitis, and they are helpful for early differential diagnosis.

Effect of fluoride on expression of phosphorylated NMDAR protein in rat hippocampal neurons / 中华地方病学杂志

Objective To observe the expression of phosphorylated N-methyl-D-aspartate receptor (P-NMDAR) protein in hippocampal neurons of rats with fluorosis and explore the mechanism of neuronal damage caused by fluorosis.Methods Sixteen Sprague-Dawley rats within 24 h after birth were selected,and hippocampus of the brain was isolated after sacrifice.The primary neurons were cultured in vitro.Observation of the cell morphology under an inverted microscope,neurons were identified by immunofluorescence staining.In the 7th day of cultivation,the neurons were divided into control group,low fluoride group,high fluoride group,antagonist group,low fluoride antagonist group and high fluoride antagonist group.The control group was treated with the same volume of medium as the experimental group.The concentration of NaF was 0.2 and 2.0 mmol/L in the low fluoride group and the high fluoride group,respectively.The antagonist group was treated with 10.0 μ mol/L NMDAR antagonist (MK-801).The low fluoride antagonist group and the high fluoride antagonist group were treated with 0.2 mmol/L NaF + 10.0 μmol/L MK-801,2.0 mmol/L NaF + 10.0 μmol/L MK-801,respectively.The culture time was 24 hours.The expression levels of phosphorylated protein (P-NMDAR1,P-NMDAR2A,P-NMDAR2B) of NMDAR subunits were detected by Western blotting.Results Under inverted microscope,the primary cell body of the cultured in vitro for 2-3 days became larger,and many protrusions appeared outward,showing a small spider shape;6-7 days,the cells synaptic long and slender,a network-like interlaced form.Under fluorescent microscope,NeuN positive cells (neurons) with red fluorescence were observed,and the cell purity exceeded 80％.There was no significant difference in the expression of P-NMDAR1 protein between the control group,the low fluoride group,the high fluoride group,the antagonist group,the low fluoride antagonist group and the high fluoride antagonist group (0.44 ± 0.12,0.46 ± 0.06,0.46 ± 0.12,0.56 ± 0.10,0.70 ± 0.12,0.46 ± 0.09,F=2.75,P ＞ 0.05);P-NMDAR2A and P-NMDAR2B protein expressions were statistically significant between the six groups (0.75 ± 0.17,0.74 ± 0.08,1.13 ± 0.27,0.87 ± 0.15,0.67 ± 0.11,0.66 ± 0.09;0.68 ± 0.24,0.66 ± 0.12,1.46 ±0.27,0.74 ± 0.16,0.56 ± 0.13,0.91 ± 0.35,F =3.68,6.11,P ＜ 0.05),and the expressions of P-NMDAR2A and P-NMDAR2B protein in high fluoride group were higher than those in the control group (P ＜ 0.05);the expressions in the high fluoride antagonist group were lower than those in the high fluoride group (P ＜ 0.05).Conclusion Excessive fluoride can increase the expressions of P-NMDAR2A and P-NMDAR2B protein of hippocampal neurons,and co-culture of MK-801 and NaF can antagonize the damage of fluoride to neurons.

Effects of pien-tze-huang on expression of NMDAR1 and GluR2 in cortex of MCAO rats / 中国药理学通报

Aim: To investigate the effects of Pien-Tze-Huang (PZH) on mRNA and protein expression of NMDAR1 and GluR2 in cortex of MCAO rats. Methods: Forty healthy adult male Sprague-Dawley rats were randomly divided into three groups: sham, MCAO, MCAO + PZH groups. The rats were subjected to focal cerebral ischemia/reperfusion with suture-occluded method. Neurological deficit testing was performed with Zea Longa scale. The volume of cerebral infarction was evaluated by TTC staining. The mRNA and protein expression of NMDAR1 and GluR2 in cortex of side cerebral ischemic tissues were determined using qPCR and Western blot analysis. Results: Compared with MCAO group, PZH significantly improved the neurological deficit, decreased the volume of cerebral infarction, and up-regulated the mRNA and protein expression of NMDAR1 and GluR2. Conclusions: PZH attenuates the down-regulation of mRNA and protein expression of NMDAR1 and GluR2 after focal cerebral ischemic injury in rats, which may be associated with the cerebral protective effect of PZH.