Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

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.

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.

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.

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.

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.

Gamma-aminobutyric acid A receptor and N-methyl-D-aspartate receptor subunit expression in rat spiral ganglion neurons

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.

Influence of tanshinone on N-methyl-D-aspartate receptor 1 protein expression in a rat model of spinal cord ischemia/reperfusion injury

BACKGROUND： Tanshinone has been previously shown to be involved in the prevention and treatment of cerebral ischemia/reperfusion injury. In addition, excitatory amino acid-mediated neu- rotoxicity may induce neuronal damage following spinal cord ischemia/reperfusion injury. OBJECTIVE： To explore the interventional effect of tanshinone on N-methyl-D-aspartate receptor 1 （NMDAR1） protein expression in a rat model of spinal cord ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized molecular biology experiment was conducted at the Traumatology ＆ Orthopedics Laboratory of Fujian Hospital of Traditional Chinese Medicine （Key Laboratory of State Administration of Traditional Chinese Medicine） between September 2007 and May 2008. MATERIALS： A total of 88 Sprague Dawley rats were randomly divided into a sham operation （n = 8）, model （n = 40）, and tanshinone （n = 40） groups. Thirty minutes after ischemia, rats in the model and tanshinone groups were observed at hour 0.5, 1, 4, 8, and 12 following perfusion, with eight rats for each time point. METHODS： Abdominal aorta occlusion was performed along the right renal arterial root using a Scoville-Lewis clamp to induce spinal cord ischemia. Blood flow was recovered 30 minutes following occlusion to establish models of spinal cord ischemia/reperfusion injury. Abdominal aorta occlusion was not performed in the sham operation group. An intraperitoneal injection of tanshinone ⅡA sulfonic sodium solution （0.2 L/g） was administered to rats in the tanshinone group, preoperatively. In addition, rats in the sham operation and model groups were treated with an intraperitoneal injection of the same concentration of saline, preoperatively. MAIN OUTCOME MEASURES： NMDAR1 protein expression in the anterior horn of the spinal cord, accumulative absorbance, average absorbance, and area of positive cells were detected in the three groups through immunohistochemistry. RESULTS： All 88 rats were included in the final analysis. （1） NMDAR1 protein expression increased following 30-minute ischemia/1-hour reperfusion injury to the spinal cord, and reached a peak 4 hours after reperfusion. （2） Accumulative absorbance and average absorbance of NMDAR1, as well as area of positive cells in the model group, were significantly greater than the sham operation group at each time point （P 〈 0.05）. However, values in the tanshinone group were significantly less than the model group （P 〈 0.05）. CONCLUSION： NMDAR1 protein expression was rapidly increased following spinal cord ischemia/reperfusion injury and reached a peak 4 hours following reperfusion. In addition, tanshinone downregulated NMDAR1 protein expression in the anterior horn of the spinal cord.

N-methyl-D-aspartate receptor expression in the spinal dorsal horn of a rat model of formalin-induced inflammatory pain following intrathecal injection of butorphanol

Clinical and animal experiments have proved that intrathecal injection of butorphanol has an analgesic effect. However, whether the analgesic effect is associated with activation of the N-methyI-D-aspartate （NMDA） receptor remains unclear. This study presumed that intrathecal injection of butorphanol has an analgesic effect on formalin-induced inflammatory pain in rats, and its analgesic effect is associated with inhibition of NMDA receptors. Concurrently, ketamine was injected into the intrathecal space, which is a non-competitive NMDA receptor antagonist, to determine the analgesic mechanism of butorphanol. The total reflection time in phase 1 and phase 2 of rat hind paws carding action was reduced when the butorphanol dose was increased to 25 μg, or a low dose of butorphanol was combined with ketamine. Intrathecal injection of a high dose of butorphanol alone or a low dose of butorphanol combined with ketamine can remarkably reduce NMDA receptor expression in the Ls spinal dorsal hom of formalin-induced pain rats. The results suggest that intrathecal injection of butorphanol has analgesic effects on formalin-induced inflammatory pain, and remarkably reduces NMDA receptor expression in the rat spinal dorsal horn Ketamine strengthens this analgesic effect. The analgesic mechanism of intrathecal injection of butorphanol is associated with inhibition of NMDA receptor activation.

Estrogen affects neuropathic pain through upregulating N-methyl-D-aspartate acid receptor 1 expression in the dorsal root ganglion of rats

Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1（NMDAR1） plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D（-）-2-amino-5-phosphonopentanoic acid（AP-5）,or both once daily for 15 days.Compared with injured drug na？ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity（as assessed by immunohistochemistry） and protein（as determined by western blot assay） in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.

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.

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.

N-methyl-D-aspartate receptor subunit 1 protein expression in the hippocampus and temporal cortex of kainic acid-induced epilepsy rats

BACKGROUND： The N-methyl-D-aspartate receptor subunit 1 （NMDAR1） contributes to the incidence of epilepsy. However, the relationship between epilepsy-induced brain injury and NMDAR1 remains poorly understood. OBJECTIVE： To investigate changes in NMDAR1 protein expression in the hippocampus and temporal cortex of kainic acid-induced epilepsy rats. DESIGN, TIME AND SETFING： A randomized, controlled, animal experiment was performed at the Department of Physiology and Department of Pathology, Basic Medical College of Jilin University from March 2002 to March 2003. MATERIALS： Rabbit anti-NMDAR1 antibody was purchased from Wuhan Boster Biological Technology, China. METHODS： A total of 80 healthy, male, Wistar rats, aged 22 weeks, were randomly assigned to sham-surgery （n = 10） and model （n = 70） groups. Epilepsy models were established by injecting kainic acid （1μL） into the right amygdala, and rats were sacrificed at 2, 6, 24, 72 hours, and 7, 15, 30 days after surgery, with 10 animals at each time point. The rats in the sham-surgery group were injected with 1μL phosphate buffered saline into the right amygdala. MAIN OUTCOME MEASURES： NMDAR1 protein expression in the hippocampus and temporal cortex at 2, 6, 24, 72 hours and 7, 15, 30 days after epilepsy was detected using immunohistochemistry and flow cytometry analysis. RESULTS： In the sham-surgery group, a few NMDARl-positive cells were distributed in the hippocampus and temporal cortex. In the model group, NMDARl-positive cells were increased in the hippocampus and temporal cortex at 2 hours following kainic acid-induced epilepsy. They were significantly increased at 6 hours, and slightly decreased at 7 days （CA3 region and temporal cortex）, but remained greater than the sham-surgery group. This continued until day 30 （P 〈 0.01 ）. In addition, there were more NMDAR1 positive cells in the hippocampal CA3 and dentate gyrus than the temporal cortex （P 〈 0.01）. CONCLUSION： In epilepsy model rats, NMDAR1 protein expression was upregulated in the hippocampus and temporal cortex, and in particular in the hippocampal CA3 and dentate gyrus. NMDAR1 may participate in epilepsy and the excitation process of the epileptic brain.

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.

N-methyl-D-aspartate receptor effects on p38 mitogen activated protein kinase and its role in a rat model of diabetic neuropathic pain

BACKGROUND： Activated N-methyl-D-aspartate （NMDA） receptor is involved in the formation of chronic neuropathic pain, and its antagonist, ketamine, exhibits effective amelioration of diabetic neuropathic pain （DNP）. However, the mechanisms of NMDA receptor participation in the formation and maintenance of DNP remain poorly understood. OBJECTIVE： To evaluate the role NMDA receptor plays in DNP and effects on p38 mitogen activated protein kinase （p38 MAPK） in a rat model of DNP. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Human Embryonic Stem Cell Research Institute of Yunyang Medical College Affiliated Taihe Hospital between July 2005 and September 2007. MATERIALS： Streptozotocin was provided by Sigma, USA; p38 MAPK inhibitor （SB203580） was provided by Shanghai KangChen Biotech, China; NMDA receptor antagonist （MK-801） was purchased from Shanghai Yope Biotech, China. METHODS： A total of 128 healthy, Wistar rats of clean grade, aged 3 months and weighing 180- 220 g, were randomly assigned to 4 groups： control, DNP model, p38 MAPK, and NMDA receptor. Each group contained 32 rats. DNP was established in all groups except for the control group by intraperitoneal injection of streptozocin （65 mg/kg）. Subsequently, 1 mg/kg SB203580 and 1 mg/kg MK-801 were injected once each week via intraperitoneal injection in the p38 MAPK and NMDA receptor groups, respectively. MAIN OUTCOME MEASURES： At the end of 2, 4, 6, and 8 weeks following streptozotocin injection, mechanical withdrawal threshold was measured in 8 animals from each group following von Frey filament stimulation. The rats were anesthetized and nerve conduction velocity of the left sciatic nerve was measured. Subsequently, the right sciatic nerve, the lumbar segment of the spinal cord, and dorsal root ganglia were removed from the L3-6 segment for microscopic examination, p38 MAPK expression was determined using immunohistochemistry and Western blot analysis. Expression of NMDA receptor 1 mRNA in dorsal root ganglion and spinal cord neurons was detected using RT-PCR. RESULTS： Mechanical withdrawal threshold and nerve conduction velocity were significantly reduced, and p38 MAPK and NMDA receptor 1 mRNA expression in the spinal cord and dorsal root ganglia were significantly increased, in the model, p38 MAPK, and NMDA receptor groups compared with the control group at all time points （P 〈 0.05）. At 4-8 weeks following successful DNP model establishment, SB203580 and MK-801 increased mechanical withdrawal threshold, accelerated nerve conduction velocity, and attenuated p38 MAPK expression, compared with the model group. The NMDA receptor group exhibited downregulated mRNA expression of NMDA receptor 1 compared with the model and p38 MAPK groups （P 〈 0.05）. CONCLUSION： NMDA receptor was highly expressed in the brains of DNP rats and was involved in DNP development via activation of the p38 MAPK signal pathway.

N-methyl-D-aspartate receptor subunit expression in memory-related brain areas of lead-exposed rats

Lead exposure induces decreased hippocampal N-methyI-D-aspartic acid （NMDA） receptor gene and protein expressions, which influences the molecular mechanisms of learning and memory. However, lead poisoning-induced differences in NMDA subunit expression, and the correlation of lead poisoning with learning and memory, remain poorly understood. The present study measured differences in expression of NMDA receptor subunits NR1, NR2A, and NR2B in memory-related brain regions of rats who underwent different doses of lead exposure. Results demonstrated decreased NR1, NR2A, and NR2B subunit expressions in some memory-related brain areas. The inhibitory effect of 4.8 mmol/L lead exposure on hippocampal NR2B was most significant, although NR2A expression also significantly decreased following 14.4 mmol/L lead exposure. There was no difference in NR1 expression following exposure to 〈 4.8 mmol/L lead, although the inhibitory effect of 19.6 mmol/L lead exposure was strongest for NR1 expression in the hippocampus. Inhibitory avoidance test results revealed that greater concentrations of lead exposure resulted in decreased learning and memory. Therefore, lead toxicity was dependent on NMDA receptor subunit composition, and NR1, NR2A, and NR2B expressions were associated with time and concentration of lead exposure.

Changes in N-methyl-D-aspartate receptor 2A subunit expression caused by binocular form deprivation and chondroitin sulfate proteoglycan degradation

Light deprivation is known to induce a significant decrease in the percentage of N-methyi-D- aspartate receptor 2A subunit （NR2A）-expressing neurons during development. The purpose of this study was to investigate the effects of binocular form deprivation （BFD） and chondroitin sulfate proteoglycan （CSPG） degradation on NR2A expression via an immunohistochemical study, around the end of a critical developmental period. The results show that the positive staining of NR2A in the normal rat visual cortex increases gradually from postnatal 3-5 weeks （P 〈 0.05）, but the changes from 5 weeks to 7 weeks were not significant. The positive staining of NR2A following BFD in the rat visual cortex slightly increased from postnatal 3-7 weeks （P 〉 0.05）. The positive staining of NR2A in the CSPG-treated group was insignificant compared with the BFD group at the same time point from 4 weeks to 7 weeks （P 〉 0.05）. Thus, the effect of BFD on NR2A expression in the rat visual cortex was similar to that of CSPG degradation around the end of the critical developmental period.

Expression of mRNA-encoding subunits of N-methyl-D-aspartate receptor in the hypothalamus in sustained monaural block of auditory air-conduction model rats

A sustained monaural block of auditory air-conduction model was established in rats through subcutaneous suture in the right ear canal.The gene expression levels of hypothalamic N-methyl-D-aspartate receptor NR1,NR2A,NR2B and NR2C mRNA in the auditory central nervous system of Sprague-Dawley rats at postnatal 9,23,37 days were determined after an environmental change.Reverse transcription-PCR assay showed that the critical period for the development of NR1,NR2A,and NR2B subunits in the left hypothalamus and NR1-and NR2B-dependent auditory neurons in the right hypothalamus terminated 23 days after the suture in the right ear.The critical period for the development of NR2A subunit-dependent auditory neurons in the right hypothalamus was terminated by postnatal day 37.The results confirmed that N-methyl-D-aspartate receptor subunits in the hypothalamus may be regulated by the auditory environment.

Dose-dependent and combined effects of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine on the survival of retinal ganglion cells in adult hamsters

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.

N-methyl-D-aspartate receptor subtype 3A promotes apoptosis in developing mouse brain exposed to hyperoxia

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.

N-methyl-D-aspartate受体阻断剂MK801对离体海马脑片CA1区锥体细胞缺氧期间电生理的影响

目的 应用细胞内记录技术 ,研究 N- methyl- D- aspartate(NMDA)受体阻断剂 MK80 1对离体海马脑片 CA1区锥体细胞缺氧期间电生理的影响。方法 成年雄性 SD大鼠海马脑片随机分为单纯缺氧组 (Con组 ,n=1 0 )和 MK80 1组 (M组 ,n=1 0 )。Con组海马脑片给予 1 0分钟缺氧 ;而 M组的海马脑片在缺氧前 1 0分钟及 1 0分钟的缺氧期间分别应用 1 0 0 μmol/ L 的 MK80 1。所有脑片均给予 6 0分钟的复氧。应用细胞内记录技术记录海马 CA1区神经元缓慢去极化及快速去极化的时间、快速去极化的幅度。在复氧末 ,应用细胞内注入电流及经 Schaffer通路刺激 ,观察神经元对刺激的反应。结果 Con组海马 CA1区锥体神经元缓慢去极化速率为 (0 .2 2± 0 .0 5 ) m V/ s,显著高于 M组的 (0 .0 8± 0 .0 3) m V/ s (P<0 .0 5 ) ;NMDA受体阻断剂 MK80 1可以显著延迟神经元的快速去极化的时间 ,M组神经元的快速去极化时间为 (5 37± 1 39) s,显著高于 Con组的 (2 6 1± 2 6 ) s (P<0 .0 5 ) ;M组 CA1区神经元的快速去极化幅度为 (4± 1 3) m V,显著小于 Con组的 (5 3± 7) m V(P<0 .0 5 )。在复氧末 ,M组的 1 0例神经元中 ,9例神经元恢复对刺激的反应。结论 NMDA受体阻断剂可显著减轻神经元的缺氧性损伤 ,促进复氧后神经元功?