• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.30 no.3
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• pp.127-131
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• 2019

Many neurologic disorders manifest as psychiatric symptoms. Anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis is an autoimmune disease of the brain characterized by numerous neurological and psychiatric features. Despite being rare, its prevalence is rapidly increasing and early management is critical in ensuring successful and sustainable recovery. Therefore, the illness should be considered as a differential diagnosis when clinically assessing patients. This report presents a case of a female child who was hospitalized for acute psychiatric manifestations, which was later confirmed as anti-NMDA receptor encephalitis. She recovered relatively successfully after combined neurological and psychiatric treatment. This report provides information on the clinical course of early onset anti-NMDA receptor encephalitis, including treatment strategy and prognosis.

• Archives of Pharmacal Research
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• v.22 no.1
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• pp.35-43
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• 1999

Overstimulation of both kainate (KA) and N-methyl-D-aspartate (NMDA) receptors has been reported to induce excitatoxicity which can be characterized by neuronal damage and formation of reactive oxygen free radicals. Neuroprotective effect of melatonin against KA-induced excitotoxicity have been documented in vitro and in vivo. It is, however, not clear whether melationin is also neuroportective against excitotoxicity mediated by NMDA receptors. In the present work, we tested the in vivo protective effects of striatally infused melatonin against the oxidative stress and neuronal damage induced by the injection of KA and NMDA receptors into the rat striatum. Melatonin implants consisting of 22-gauge stainless-steel cannule with melatonin fused inside the tip were placed bilaterally in the rat brain one week prior to intrastriatal injection of glutamate receptor subtype agonists. Melatonin showed protective effects against the elevation of lipid peroxidation induced by either KA or NMDA and recovered Cu, Zn-superoxide dismutase activities reduced by both KA and NMDA into the control level. Melatonin also clearly blocked both KA- and NMDA-receptor mediated neuronal damage assessed by the determination of choline acetyltransferase activity in striatal monogenages and by microscopic observation of rat brain section stained with cresyl violet. The protective effects of melatonin are comparable to those of DNQX and MK801 which are the KA- and NMDA-receptor antagonist, respectively. It is suggested that melatonin could protect against striatal oxidative damages mediated by glutamate receptors, both non-NMDA and NMDA receptors.

• Journal of Acupuncture Research
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• v.20 no.3
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• pp.15-23
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• 2003

Objective : The role of high frequency 120 Hz electroacupuncture(EA) in carrageenan-induced pain was studied by examining the alnalgesic effects, and prostaglandin $E_2(PGE_2)$ levels measurement and spinal N-methyl-D-aspartate(NMDA) receptor expression. Inflammation was induced by an intraplantar injection of 1% carrageenan into the right hind paw. Method : Bilateral EA stimulation with 120 Hz were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via the needles for a total of 30 min duration in carrageenan-injected rats. Results : EA stimulation showed significant analgesic effects as measured by analgesy-meter at all time points tested compared with controls. Three hours after carrageenan injection, PGE2 levels were measured by commercial kit. EA significantly inhibited PGE2 production in the right paw. The number of NR1 and NR2A, NMDA receptor, immunoreactive neurons was significantly increased in the superficial dorsal horn(laminae I-II) and nucleus proprius(laminae III-IV) of ipsilateral spinal cord at L4-5. But the number of carrageenan-induced NR1 and NR2A immunoreactive neuron, especially NR1 immunoreaction in the superficial dorsal horn, was reduced by 120 Hz EA stimulation. Conclusions : These results indicate that NMDA receptors may mediate transmission of nociceptive information originating in tissue inflammation of hind paw and high frequency 120 Hz EA stimulation have an alleviating action against local inflammatory pain.

• The Korean Journal of Pain
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• v.24 no.1
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• pp.53-56
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• 2011

Although postherpetic neuralgia (PHN) is a common chronic pain syndrome, the pathophysiology of this disorder is not well known and management is often very difficult. N-methyl-D-Aspartate (NMDA) receptor antagonists are known to be effective in PHN, and magnesium, a physiological blocker of NMDA receptors, is widely used to treat various chronic pain disorders. Here, we present a case of the PHN refractory to conventional treatment, which was treated successfully with transforaminal epidural injection of magnesium sulphate at the affected dermatome.

• Neonatal Medicine
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• v.16 no.2
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• pp.221-233
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• 2009

Purpose: Erythropoietin (EPO) has neuroprotective effects in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity. Current studies have demonstrated the neuroprotective effects of EPO, but limited data are available for the neonatal periods. Here in we investigated whether recombinant human EPO (rHuEPO) can protect the developing rat brain from HI injury via modulation of NMDA receptors. Methods: In an in vitro model, embryonic cortical neuronal cell cultures from Sprague-Dawley (SD) rats at 19-days gestation were established. The cultured cells were divided into five groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated (H+E1, H+ E10, and H+E100) groups. To estimate cell viability and growth, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was done. In an in vivo model, left carotid artery ligation was performed on 7-day-old SD rat pups. The animals were divided into six groups; normoxia control (NC), normoxia Sham-operated (NS), hypoxia-ischemia only (H), hypoxia-ischemia+vehicle (HV), hypoxia-ischemia+rHuEPO before a HI injury (HE-B), and hypoxia-ischemia+rHuEPO after a HI injury (HE-A). The morphologic changes following brain injuries were noted using hematoxylin and eosin (H/E) staining. Real-time PCR using primers of subunits of NMDA receptors (NR1, NR2A, NR2B, NR2C and NR2D) mRNA were performed. Results: Cell viability in the H group was decreased to less than 60% of that in the N group. In the H+E1 and H+E10 groups, cell viability was increased to >80% of the N group, but cell viability in the H+E100 group did not recover. The percentage of the left hemisphere area compared the to the right hemisphere area were 98.9% in the NC group, 99.1% in the NS group, 57.1% in the H group, 57.0% in the HV group, 87.6% in the HE-B group, and 91.6% in the HE-A group. Real-time PCR analysis of the expressions of subunits of NMDA receptors mRNAs in the in vitro and in vivo neonatal HI brain injuries generally revealed that the expression in the H group was decreased compared to the N group and the expressions in the rHuEPO-treated groups was increased compared to the H group. Conclusion: rHuEPO has neuroprotective property in perinatal HI brain injury via modulation of N-methyl-D-aspartate receptors.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.3
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• pp.179-186
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• 2005

Whole bee venom (WBV) and its major component, melittin, have been reported to induce long-lasting spontaneous flinchings and hyperalgesia. The current study was designed to elucidate the peripheral and spinal mechanisms of N-methyl-D-aspartate (NMDA) and non-NMDA receptors by which intraplantar (i.pl.) injection of WBV and melittin induced nociceptive responses. Changes in mechanical threshold and flinching behaviors were measured after the injection of WBV (0.04 mg or 0.1 mg/paw) and melittin (0.02 mg or 0.05 mg/paw) into the mid-plantar area of a rat hindpaw. MK-801 and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione disodium) were administered intrathecally (i.t. $10{\mu}g$) or i.pl.($15{\mu}g$) 15 min before or i.t. 60 min after i.pl. WBV and melittin injection. Intrathecal pre- and postadministration of MK-801 and CNQX significantly attenuated the ability of high dose WBV and melittin to reduce paw withdrawal threshold (PWT). In the rat injected with low dose, but not high dose, of WBV and melittin, i.pl. injection of MK-801 effectively suppressed the decrease of PWTs only at the later time-points, but the inhibitory effect of CNQX (i.pl.) was significant at all time-point after the injection of low dose melittin. High dose WBV- and melittin-induced spontaneous flinchings were significantly suppressed by i.t. administration of MK-801 and CNQX, and low dose WBV- and melittin-induced flinchings were significantly reduced only by intraplantarly administered CNQX, but not by MK-801. These experimental flinchings suggest that spinal, and partial peripheral mechanisms of NMDA and non-NMDA receptors are involved in the development and maintenance of WBV- and melittin-induced nociceptive responses.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.425-429
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• 2009

Intracranial headaches, including migraines, are mediated by nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. We previously demonstrated that selective blockage of spinal sigma-1 receptors (Sig-1R) produces a prominent antinociceptive effect in several types of pain models. This study evaluates whether the Sig-1R antagonist (BD1047) has an antinociceptive effect on capsaicin (a potent C-fiber activator) induced headache models in rats. Intracisternal infusion of capsaicin evoked pain behavior (face grooming), which was significantly attenuated by BD1047 pretreatment. BD1047 consistently reduced capsaicin-induced Fos-like immunoreactivity (Fos-LI), a neuronal activator, in the TNC in a dose-dependent manner. Moreover, capsaicininduced phosphorylation of N-methyl-D-aspartate receptor subunit 1 was reversed by BD1047 pretreatment in the TNC. These results indicate that the Sig-1R antagonist has an inhibitory effect on nociceptive activation of the TNC in the capsaicin-induced headache animal model.

• Archives of Pharmacal Research
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• v.18 no.6
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• pp.391-395
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• 1995

Several lines of evidence indicate that physiological activity of N-methyl-D-aspartate (NMDA) receptor was blocked by physiological concentration of $Mg^{2+}$ (1.2 mM). However, the activity of NMDA receptor may not be blocked totally with this concentration of $Mg^{2+}$ under elevated membrane potential by kainate. Here, we described the effect of $Mg^{2+}$ on NMDA receptor and how much of NMDA receptor functions could be activated by kainate. Effects of NMDA receptor antagonist on kainate-induced elevation of intracellualr $Ca^{2+}$ levels $([Ca^{2+}]_i)$ and extracellular glutamate level were examined in cultured rat cerebellar granule neurons. kainate-induced elevation of $([Ca^{2+}]_i)$ was not affected by physiological concentration of $Mg^{2+}$. Kainate-induced NMDA-induced elevation was blocked by the same concentration of $MG^{2+}$Kainate-induced elevation of [$([Ca^{2+}]_i)$ was decreased by 32% in the presence of NMDA antagonists, MK-801 and CPP (3-[2-carboxypiperazine-4-yl]propyl-1-phosphonic acid), in $Mg^{2+}$ free buffer. Kainate receptor-activated gluamate release was also decreased (30%) by MK-801 or CPP. These resuts show that certain extent of elevations of intracellular $Ca^{2+}$ and extracellular glutamate by kainate is due to coativation of NMDA receptors.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.102-102
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• 1997

The purpose of this study was to determine the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both the competitive (AP-5 and D-CPP) and the noncompetitive (MK-801, ketamine, dextrorphan and dextromethorphan) N-methyl-D-aspartate (NMDA) receptor antagonists markedly enhanced 5-HT(5-hydroxytryptamine)-induced selective serotonergic behavior, head-twitch response (HTR), in mice. These results suggest that the glutamatergic neurotransmission may modulate serotonergic function at the 5-HT receptor. The precise relationship between glutamatergic and serotonergic system is as yet undefined. However, these are the first data available regarding glutamatergic modulation of serotonergic function at the 5-HT receptor in intact mice, and the present results support the notion that the NMDA receptors may play important roles in the glutamatergic modulation of serotonergic function at the 5-HT receptor.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.113-118
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• 1999

Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic $5-HT_{2}$ receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompeti-tive (MI-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsyaptic $5-HT_{2}$receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin $5-HT_{2}$receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the poststynaptic $5-HT_{2}$ receptors.