IL-17A exacerbates diabetic retinopathy by impairing Müller cell function via Act1 signaling

Diabetic retinopathy (DR), one of the most serious complications of diabetes, has been associated with inflammatory processes. We have recently reported that interleukin (IL)-17A, a proinflammatory cytokine, is increased in the plasma of diabetic patients. Further investigation is required to clarify the role of IL-17A in DR. Ins2(Akita) (Akita) diabetic mice and high-glucose (HG)-treated primary Müller cells were used to mimic DR-like pathology. Diabetes induced retinal expression of IL-17A and IL-17 receptor A (IL-17RA) in Müller cells in contrast to ganglion cells. Further evidence demonstrated that retinal Müller cells cultured in vitro increased IL-17A and IL-17RA expression as well as IL-17A secretion in the HG condition. In both the HG-treated Müller cells and Akita mouse retina, the Act1/TRAF6/IKK/NF-κB signaling pathway was activated. IL-17A further enhanced inflammatory signaling activation, whereas Act1 knockdown or IKK inhibition blocked the downstream signaling activation by IL-17A. HG- and diabetes-induced Müller cell activation and dysfunction, as determined by increased glial fibrillary acidic protein, vascular endothelial growth factor and glutamate levels and decreased glutamine synthetase and excitatory amino acid transporter-1 expression, were exacerbated by IL-17A; however, they were alleviated by Act1 knockdown or IKK inhibition. In addition, IL-17A intravitreal injection aggravated diabetes-induced retinal vascular leukostasis, vascular leakage and ganglion cell apoptosis, whereas Act1 silencing or anti-IL-17A monoclonal antibody ameliorated the retinal vascular damage and neuronal cell apoptosis. These findings establish that IL-17A exacerbates DR-like pathology by the promotion of Müller cell functional impairment via Act1 signaling.

Effect of Acorus tatarinowii Schott on the amino acid neurotransmitters in the striatum focal cerebral ischemia in rat / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To research the change of concentration of the amino acid neurotransmitters in the striatum focal cerebral ischemia in rat and the effect of Acorus tatarinowii Schott, one of inducing resuscitation drugs, for 4 of amino acid neurotransmitters.</p><p><b>METHODS</b>Twenty four rats were divided into four groups (n = 6): control group, cerebral ischemia group, sham operation group and Acorns tatarinowii Schott treated group. Rats were established into models of cerebral ischemia by occluding bilateral thread cork method. Formation sampling were performed in a striatum area using microdialysis and the detection of biological sample including aspartic acid, glutamic acid, glycine and gamma-aminobutyric acid by high performance liquid chromatography (HPLC) electrochemical detector system.</p><p><b>RESULTS</b>Compared with the control, the all contents of 4 kinds of the amino acids were significantly increased during cerebral ischemia (P < 0.01). Compared with the cerebral ischemia group, the contents of aspartic acid, glutamic acid that were excitatory amino acids were remarkably decreased in the striatum for Acorus tatarinowii Schott treated group (P < 0.01), It was no significant influence on gamma-aminobutyric acid and glycine that belonged to inhibitory amino acid in a nascent condition but with a elevating in the later period of microdialysis.</p><p><b>CONCLUSION</b>Acorus tatarinowii Schott can enter the cerebral parenchyma through blood brain barrier and cut down glutamic acid,aspartic acid increased during cerebral ischemia. As a result, the neurotoxicity attributed to the excitatory amino acid has been released in excessive amounts declined so as to avoid the secondary impairment of neurons caused by excitatory amino acids pernicious effects after ischemia. It may be one of the protective mechanism of drugs for inducing resuscitation resembling EAA receptor antagonists to ischemi brain.</p>

Research progress on periventricular white matter damage pathogenesis in preterm infants / 中国当代儿科杂志

Periventricular white matter damage is one of the characteristics of brain damage in preterm infants, and it is the most important type of encephalopathy. The pathological changes including the white matter of coagulation necrosis, oligodendrocyte damage, myelin damage, axonal injury and reactive gliosis and microglia infiltration in necrotic areas. All of these lesions are closely related to the nervous system sequelae in later-neonatal period. The pathogenesis of periventricular leukomalacia in premature infants are mainly cause by its immature brain vascular, and precursor oligodendrocytes of the attack of hypoxia, ischemia, infection, oxygen free radicals, inflammatory cytokines, increasing glutamate, and other high-risk factors. In this paper, an overview of progress in the study of the pathogenesis of periventricular white matter damage in premature infants through literature review to provide a theoretical support for clinical prevention, diagnosis and treatment.

Effect of sildenafil citrate on behavior and excitatory and inhibitory amino acids levels in albino rat's brain

Sildenafil is an active cGMP-specific phosphodiesterase type 5 inhibitor that is effective in the treatment of male erectile dysfunction. None of the previous studies have measured sildenafil or its possibly related neurochemical changes, but mainly they related their finding to sildenafil associated behavior changes. In this work, behavioral and brain neurochemical changes [excitatory and inhibitory neurotransmitters] associated with acute administration of sildenafil using male albino rats were investigated. Rats were divided into three groups [n=6]; group1 received saline [1ml/kg], group 2 received single doses of sildenafil [1.5mg/kg], while group 3 received single doses of sildenafil [100mg/kg]. Administration was via the intraperitoneal route. Behavior scores using EPM and brain homogenate for neurotransmitters evaluation by HPLC were carried out 60min after administration. Sildenafil did not produce any changes in behavior using the EPM test; also it did not alter the brain levels of excitatory, inhibitory and dopamine. Sildenafil produced dose dependent decreases in plasma dopamine level by mechanism[s] needs more neurochemical investigation. The chronic effect of sildenafil should be taken into consideration.

Pathophysiology of neurodegeneration following traumatic brain injury / Patofisiología de la neurodegeneración tras una lesión traumática del cerebro

Acute neuropathological conditions, including brain and spinal cord trauma, are leading causes of death and disabilities worldwide, especially in children and young adults. The causes of brain and spinal cord injuries include automobile accidents, accidents during recreational activities, falls and violent attacks. In the United States of America alone, around 1.7 million people each year seek medical care for some kind of head injury. About fifty-two thousand of these people will die, while the same number will present with permanent functional disability. Considering the high worldwide prevalence of these acute pathological conditions, research on the mechanisms underlying central nervous system damage is of extreme importance. Nowadays, a number of experimental models of acute neural disorders have been developed and the mechanisms of tissue loss have been investigated. These mechanisms include both primary and secondary pathological events contributing to tissue damage and functional impairment. The main secondary pathological mechanisms encompass excitotoxicity, ionic imbalances, inflammatory response, oxidative stress and apoptosis. The proper elucidation of how neural tissue is lost following brain and spinal cord trauma is fundamental to developing effective therapies to human diseases. The present review evaluates the main mechanisms of secondary tissue damage following traumatic brain and spinal cord injuries.

Las condiciones neuropatológicas agudas, incluyendo los traumas del cerebro y la médula espinal, se hallan entre las principales causas de muerte y discapacidades a nivel mundial, sobre todo en niños y adultos jóvenes. Las causas de las lesiones del cerebro y la médula espinal, incluyen los accidentes automovilísticos, accidentes en actividades recreativas, caídas y ataques violentos. Sólo en los Estados Unidos de Norte América, alrededor de 1.7 millones de personas buscan anualmente atención médica para algún tipo de lesión craneal. Cincuenta y dos mil de estas personas morirán, mientras que un número similar presentará alguna discapacidad funcional permanente. Dada la alta prevalencia de estas condiciones patológicas agudas a nivel mundial, la investigación de los mecanismos que subyacen en los daños al sistema nervioso central, constituye un asunto de suma importancia. Hoy día, se han desarrollado varios modelos experimentales de trastornos neurales agudos, y se han investigado los mecanismos de la pérdida de tejido. Estos mecanismos incluyen tanto las manifestaciones patológicas primarias como las secundarias, que contribuyen al daño del tejido y al deterioro funcional. Los mecanismos patológicos secundarios principales abarcan la excitotoxicidad, los desequilibrios iónicos, la respuesta inflamatoria, el estrés oxidativo, y la apoptosis. Dilucidar correctamente como ocurre la pérdida del tejido neuronal luego del trama del cerebro o la médula espinal, es fundamental para poder desarrollar terapias efectivas en relación con las enfermedades humanas. La presente revisión evalúa los mecanismos principales del daño secundario al tejido, tras las lesiones traumáticas del cerebro y la médula espinal.

Study on 3'-methoxy puerarin to dynamic changes of amino acids in rat brain ischemia-reperfusion / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of 3'-methoxy puerarin on cerebral ischemic glutamic acid, aspartic acid, taurine and gamma-aminobutyric acid inhibitory of rats and investigate the protective mechanisms of cerebral ischemia-reperfusion.</p><p><b>METHOD</b>Using middle cerebral artery occlusion rat model, to collect extracellular fluid in rat striatal amino acid neurotransmitters by brain microdialysis and HPLC techniques with fluorescence detection before and after 3'-methoxy puerarin treatment four kinds of amino acids changes.</p><p><b>RESULT</b>3'-methoxy puerarin reduced concentrations of excitatory amino acid (EAA) Asp and Glu, while Tau and GABA inhibitory amino acids were significantly reduced.</p><p><b>CONCLUSION</b>3'-methoxy puerarin reduce ischemia-induced brain EAA toxicity against EAA neurotoxicity, regulate the brain neurotransmitter amino acid content, improve the excitatory and inhibitory amino acid balance is one of the mechanisms that to improve and protect the important acute cerebral infarction in rat brain nuclei.</p>

Involvement of excitatory amino acid system in astrocytes activation caused by dimethoate / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the involvement of excitatory amino acid system in astrocytes activation caused by dimethoate.</p><p><b>METHODS</b>Pure-cultured astrocytes were gained by three passages from primary cultured rat nerve cells, then treated with 10(-6),10(-5),10(-4) mol/L dimethoate for 48 h, 50 micromol/L and 100 micromol/L MK801, a NMDA receptor blocker, was used to intervene the effects induced by 10(-4) mol/L dimethoate. HPLC-FLD was utilized to measure the concentrations of excitatory amino acid (EAA), RT-PCR was used to detect the expression levels of NR2B, GLT-1, GLAST, GFAP and S100beta mRNA, and immunofluorescence staining method was applied to measure the expression levels of GFAP and S100beta proteins.</p><p><b>RESULTS</b>The expression levels of GLAST mRNA in all exposure groups were 67.8%, 68.6% and 76.2% of control level, respectively, which were significantly lower than that of control group (P < 0.05); The concentrations of EAA significantly decreased in 10(-4) mol/L dimethoate group, as compared with control group (P < 0.01); the expression levels of GFAP mRNA in 10(-4) mol/L dimethoate group, of S100beta mRNA in 10(-5) mol/L dimethoate group, of GFAP protein in 10(-4) mol/L and 10(-5) mol/L dimethoate groups and S100beta protein in 10(-4) mol/L dimethoate group were significantly higher than those in control group (P < 0.01). The expression levels of GLT-1 and GLAST mRNA in 10(-4) mol/L dimethoate plus 50 micromol/L or 100 micromol/L MK801 groups increased significantly, as compared with 10(-4) mol/L dimethoate group (P < 0.01), the expression levels of NR2B mRNA in 10(-4) mol/L dimethoate plus 50 micromol/L or 100 micromol/L MK801 groups increased significantly, as compared with control group (P < 0.05 or P < 0.01); the concentration of Glu in 10(-4) mol/L dimethoate plus 100 micromol/L MK801 group increased significantly, as compared with 10(-4) mol/L dimethoate group (P < 0.01); the expression levels of GFAP mRNA and protein in 10(-4) mol/L dimethoate plus 50 micromol/L or 100 micromol/L MK801 groups decreased significantly (P < 0.01); S100beta protein expression level in 50 micromol/L MK801 intervention group was significantly higher than thatl in control group (P < 0.01).</p><p><b>CONCLUSION</b>Excitatory amino acid system involved in astrocytes activation caused by dimethoate. MK801 was useful to control astrocytes gliosis.</p>

Comparison of the Spinal Neuropathic Pain Induced by Intraspinal Injection of N-Methyl-D-Aspartate and Quisquate in Rats

OBJECTIVE: Excitatory amino acids play important roles in the development of secondary pathology following spinal cord injury (SCI). This study was designed to evaluate morphological changes in the dorsal horn of the spinal cord and assess profiles of pain behaviors following intraspinal injection of N-methyl-D-aspartate (NMDA) or quisqualate (QUIS) in rats. METHODS: Forty male Sprague-Dawley rats were randomized into three groups : a sham, and two experimental groups receiving injections of 125 mM NMDA or QUIS into their spinal dorsal horn. Following injection, hypersensitivity to cold and mechanical stimuli, and excessive grooming behaviors were assessed serially for four weeks. At the end of survival periods, morphological changes in the spinal cord were evaluated. RESULTS: Cold allodynia was developed in both the NMDA and QUIS groups, which was significantly higher in the QUIS group than in the NMDA group. The mechanical threshold for the ipsilateral hind paw in both QUIS and NMDA groups was significantly lower than that in the control group. The number of groomers was significantly higher in the NMDA group than in the QUIS group. The size of the neck region of the spinal dorsal horn, but not the superficial layer, was significantly smaller in the NMDA and QUIS groups than in the control group. CONCLUSION: Intraspinal injection of NMDA or QUIS can be used as an excitotoxic model of SCI for further research on spinal neuropathic pain.

Effect of polydatin on dynamic changes of excitatory amino acids in cerebrospinal fluid of cerebral hemorrhage rats / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effects of polydatin on dynamic changes of excitatory amino acids in cerebrospinal fluid and water content of brain tissue of cerebral hemorrhage rats. And to discuss the therapeutic action and mechanisms of polydatin on brain hemorrhagic injured rats.</p><p><b>METHOD</b>A quantitative determination method of Asp and Glu was established by microdialysis-HPLC. The cerebral hemorrhage model in rats was induced by local injection of type VII collagenase. The dynamic changes of Asp and Glu in cerebrospinal fluid were observed on 0, 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 h of cerebral hemorrhage rats, and then the water content of brain tissue was detected.</p><p><b>RESULT</b>The content of Asp and Glu increased rapidly within 24 h after cerebral hemorrhage, and to the highest in 24 h, then decreased gradually. Compared with the cerebral hemorrhage model group, the content of Asp and Glu increased slowly in polydatin group, and there were significant differences in 12-72 h and 6-84 h (P < 0.01, P < 0.05), but there was no significant difference after 84 h and 96 h. Compared with sham group, water content of brain tissue significantly higher in model group, while significantly lower (P < 0.01) in polydatin group.</p><p><b>CONCLUSION</b>Polydatin can inhibit increasing content of Asp and Glu in cerebrospinal fluid dynamics, and significantly inhibit cerebral edema of cerebral hemorrhage rats. It shows that the mechanisms of anti-cerebral hemorrhage injury of polydatin may be related to increasing of excitatory amino acids after cerebral hemorrhage.</p>

The Effect of Extracellular Glutamate Release on Repetitive Transient Ischemic Injury in Global Ischemia Model

During operations, neurosurgeons usually perform multiple temporary occlusions of parental artery, possibly resulting in the neuronal damage. It is generally thought that neuronal damage by cerebral ischemia is associated with extracellular concentrations of the excitatory amino acids. In this study, we measured the dynamics of extracellular glutamate release in 11 vessel occlusion (VO) model to compare between single occlusion and repeated transient occlusions within short interval. Changes in cerebral blood flow were monitored by laser-Doppler flowmetry simultaneously with cortical glutamate level measured by amperometric biosensor. From real time monitoring of glutamate release in 11 VO model, the change of extracellular glutamate level in repeated transient occlusion group was smaller than that of single occlusion group, and the onset time of glutamate release in the second ischemic episode of repeated occlusion group was delayed compared to the first ischemic episode which was similar to that of single 10 min ischemic episode. These results suggested that repeated transient occlusion induces less glutamate release from neuronal cell than single occlusion, and the delayed onset time of glutamate release is attributed to endogeneous protective mechanism of ischemic tolerance.

Effect of dimethoate on primary cultured rat cortical neuron / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect and mechanisms of dimethoate on the primary cultured cortical neuronal cell injury.</p><p><b>METHODS</b>Cortical neuronal cells were isolated and cultured in serum free medium for 6 days in vitro, and 1, 5, 10, 50 and 100 micromol/L dimethoate were added to the medium and intracellular SOD, MDA and GSH. The content of excitatory amino acid was measured after 48 hours. Flow cytometry was used to detect the neuronal cell apoptosis.</p><p><b>RESULTS</b>After 48 h, the activity of SOD and the content of GSH decreased [(1.04 +/- 0.02), (0.99 +/- 0.02), (0.96 +/- 0.02), (0.91 +/- 0.02) U/mg pro] [(219.35 +/- 6.79), (205.6 +/- 6.29), (194.06 +/- 2.63), (93.68 +/- 7.56) mg/g pro], and the content of MDA increased obviously with 5, 10, 50 and 100 micromol/L dimethoate [(21.22 +/- 0.29), (24.01 +/- 0.34), (27.15 +/- 1.02), (32.91 +/- 1.39) nmol/mg pro]; The content of Asp from 10 to 100 micromol/L dose group was higher than the control group and the content of Glu from 1 to 100 micromol/L dose group was higher than the control group. The apoptosis rate had great significance between 1 to 100 micromol/L dose groups and control group. When treated with dimethoate, MDA content in neuron was positively correlated with the content of EAAs with the increase of dimethoate. The correlative coefficient was 0.937 and 0.759 respectively (P < 0.01), while it was negatively correlated with the content of GSH. The correlative coefficient was -0.868 and -0.801 respectively (P < 0.01).</p><p><b>CONCLUSION</b>The oxidative damage and changes of excitatory amino acid content induced by Dimethoate contribute to the primary cultured rat cortical neuron apoptosis.</p>

Detección de la subunidad NMDAR-1 del receptor N-metil-D-asparato (NMDAR) en el hipotálamo del ovino mediante el análisis de Western blot / Detection of the N-methyl-D-asparate receptor subunit-1 (NMDAR-1) in the hypothalamus of the sheep bye Western blot analysis

Los aminoácidos excitatorios (AAEs), L-glutamato y aspartato, son considerados las principales sustancias endógenas neuroactivas involucradas en la transmisión excitatoria. El receptorN-metíl-D-aspartato (NMDAR) es uno de los principales receptores de los AAEs. Este receptor estimula la secreción de la hormona luteinizante (LH) al facilitar la secreción de la hormona liberadora de las gonadotrofinas (GnRH). En este estudio se plantearon dos objetivos: Estandarizar la técnica de Western blot para identificar la subunidad-1 del NMDAR (NMDAR-1) en hipotálamo del ovino; y determinar si existe diferencia en la distribución de la NMDAR-1 en los diferentes cuadrantes hipotalámicos (cuadrantes dorsal-rostral, ventral-rostral, dorsal-caudal, y ventral-caudal) del ovino. Se utilizaron 100 µg de proteína total para identificar la NMDAR-1 en el hipotálamo ovino. Se evidenció un efecto del cuadrante o porción del hipotálamo ovino sobre la expresión proteica de la NMDAR-1. En particular, el cuadrante dorsal-rostral (31,5567 densidad óptica ± 13,0831;P<0,05) expresó más cantidad del receptor que el cuadrante ventral caudal (17,1517 densidad óptica ± 13,0831; P<0,05) y que el cuadrante ventral-rostral (16,4683 densidad óptica ±13,0831; P<0,05). Estos resultados demuestran que el receptor NMDA se expresa más en la región rostral del hipotálamo del ovino, área en la cual se encuentran distribuidos los cuerpos celulares y axones de las neuronas productoras de GnRH. Estos resultados sugieren la participación de la vía glutamatérgica en la regulación de la reproducción de los ovinos.

The excitatory amino acids (EAAs), L-glutamate and aspartate, are considered the major endogenous neuroactive substances involved in excitatory neurotransmission. The N-methyl-D-aspartate receptor (NMDAR) is one of the main excitatory amino acid receptors. Exogenous activation of the NMDAR results in the release of gonadotrophin-releasing hormone (GnRH) from the hypothalamus and subsequent release of luteinizing hormone (LH) from the anterior pituitary. The present study had two aims: to standardize the optimal amount of total protein required to identify the NMDAR subtype-1 (NMDAR-1) in the hypothalamus of the sheep; to determine whether a difference exists in the distribution of NMDAR-1 in different hypothalamic regions (dorsal-rostral, ventral-rostral, dorsal-caudal, and ventral-caudal quadrant) in male sheep. The optimal amount of total hypothalamic protein required to visualize the NMDAR-1 was 100 µg. There was an effect of quadrant on the expression of NMDAR-1 in the hypothalamus of the intact male sheep. In particular, dorsal-rostral quadrant (31.5567 optical density ± 13.0831) expressed more receptor than ventral-caudal quadrant (17.1517 optical density ± 13.0831; P<0.05) and ventral-rostral quadrant (16.4683 optical density ± 13.0831; P<0.05). These data suggest that NMDAR is more expressed in the rostral area of the hypothalamus, where the cell bodies and axons of the GnRH neurons are localized. Thus, these data allow suggest that glutamatergic pathway potentially is involved in modulating the reproductive activity in the ovine.

Curative effect and possible mechanisms of topiramate in treatment of Tourette syndrome in rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>The pathogenesis of Tourette syndrome (TS) is associated with the disorders of neurotransmitters, such as dopamine (DA) and excitatory amino acids (EAA). Antiepileptic drugs such as topiramate have shown some effects on TS, but the mechanism has not been clearly identified. The objective of the research was to evaluate the relationship between the pathogenesis of TS and abnormality of neurotransmitters by determining the levels of brain free DA and plasma EAA in iminodipropionitrile (IDPN) induced head twitch response (HTR) rats, and to investigate the effects of topiramate on HTR induced by IDPN.</p><p><b>METHODS</b>Forty-eight Sprague-Dawley rats were randomly divided into six groups: blank control, TS model, and haloperidol-(0.5 mg/kg) and topiramate-treated (5, 10 and 20 mg/kg). HTR was induced by 7-day peritoneal injections of IDPN (150 mg/kg daily) and was used as TS model. Brain free DA levels and plasma levels of EAA were measured using ELISA and high performance liquid chromatography respectively 35 days after haloperidol or topiramate administration.</p><p><b>RESULTS</b>Brain free DA levels were significantly lower and plasma EAA levels were significantly higher in the TS model group compared with those in the blank control group (P<0.05). Topiramate of 10 and 20 mg/kg significantly decreased the frequency of IDPN-induced HTR and significantly increased the level of brain free DA when compared with the TS model group (P<0.05). Topiramate of 20 mg/kg treatment as haloperidol treatment significantly decreased plasma EAA levels compared with the TS model group (P<0.05).</p><p><b>CONCLUSIONS</b>The pathogenesis of TS is related to the super-sensitivity of DA receptor in the center nervous system and the over-effect of plasma EAA. Topiramate can reduce IDPN-induced HTR, probably through the inhibition of DA and DA-receptor combination in the brain and the secretion and release of plasma EEA.</p>

Inhibition of excitatory amino acid efflux contributes to protective effects of puerarin against cerebral ischemia in rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate whether the protective effects of puerarine (Pur) against cerebral ischemia is associated with depressing the extracellular levels of amino acid transmitters in brain of rats.</p><p><b>METHODS</b>Male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) for 60 min followed by 24 h reperfusion. Pur (50, 100 mg/kg, i.p.) was administered at the onset of MCAO. The infarct rate and edema rate were detected on TTC (2,3,5-triphenyltetrazolium chloride)-stained coronal sections. The extracellular levels of amino acid transmitters were monitored in striatum of rats with ischemic/reperfusion injury using in vivo microdialysis technique. Furthermore, the protective effects of Pur against glutamate-induced neurotoxicity were detected. Glutamate-induced apoptotic and necrotic cells in hippocampus were estimated by flow cytometric analysis of Annexin-V and PI labeling cells.</p><p><b>RESULTS</b>Pur (100 mg/kg) significantly decreased infarct size by 31.6% (P<0.05), reduced edema volume (P<0.05), and improved neurological functions (P<0.05) following MCAO. In these rats, the ischemia-induced extracellular levels of aspartate (Asp), glutamate (Glu), y-aminobutyric acid (GABA), and taurine (Tau) were significantly reduced in striatum of vehicle-treated animals by 54.7%, 56.7%, 75.8%, and 68.1% (P<0.01 and P<0.05). Pur reduced the peak values of Glu and Asp more obviously than those of GABA and Tau, and the rate of Glu/GABA during MCAO markedly decreased in Pur-treated MCAO rats, compared with the vehicle-treated MCAO rats. Meanwhile, apoptosis and necrosis induced by Glu in cultured hippocampal neurons were significantly reduced after Pur treatment.</p><p><b>CONCLUSION</b>Acute treatment with Pur at the onset of occlusion significantly depresses ischemia-induced efflux of amino acids, especially, excitotoxicity in the striatum, a mechanism underlying the neuroprotective effect on cellular survival.</p>

Spinal release of the amino acids with a time course in a rat model of postoperative pain / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The mechanisms underlying postoperative pain remain unclear. Neurotransmitters of excitatory and inhibitory amino acids play an important role in the transmission and modulation of pain in the spinal dorsal horn. This study aimed to investigate the changes of release of excitatory and inhibitory amino acids in the spinal cord during postoperative pain and to provide a novel theoretical basis for postoperative pain management.</p><p><b>METHODS</b>Loop microdialysis catheters were implanted subarachnoidally via the atlanto-occipital membrane in 16 healthy Sprague-Dawley rats. All rats without neural deficits were divided into two groups, Group A and Group B, following 5 days of recovery. The tubes for microdialysis were connected and 25 microl microdialysate sample for baseline value was collected after one-hour washout in each rat. A plantar incision in the right hind paws of rats in Group A were performed under 1.2% isoflurane. All rats in Group B were only anesthetized by 1.2% isoflurane for the same duration. The microdialysate samples were collected at 3 hours, 1 day, 2 days and 3 days after the incision (or isoflurane anesthesia in Group B) in both groups. The cumulative pain scores were also assessed at the above time-points. The amino acids in the microdialysate samples were tested using high performance liquid chromatography.</p><p><b>RESULTS</b>Within Group A, the release of aspartate and glutamate at 3 hours after the incision was significantly higher than the baseline values and the release of glycine at 1 day after the incision significantly increased compared with the baseline values (P < 0.01). Within Group B, the release of neurotransmitters at each time point had no significant difference compared with the baseline values (P > 0.05). The release of aspartate and glutamate at 3 hours after the incision in Group A was significantly higher than that in Group B (P < 0.01). The release of glycine at 1 day after the incision in Group A significantly increased compared with Group B (P < 0.01). The cumulative pain scores at 3 hours, 1 day and 2 days after the incision in Group A were significantly higher than those in Group B (P < 0.01).</p><p><b>CONCLUSIONS</b>The release of the excitatory amino acids occurs in the early phase of postoperative pain and might not be involved in the maintenance of pain in a rat model of incision pain. The release of inhibitory glycine lagged behind the excitatory amino acids. The implication of inhibitory glycine release remained to be established further.</p>

Excitatory aminoacid neurotransmitters in schizophrenia.

The study presents for the first time the blood level of glutamate and aspartate in schizophrenic patients and in normal subjects in Bangladeshi population. The serum level of glutamate and aspartate were measured in thirty newly diagnosed schizophrenic patients and the same number of subjects matching age was taken from non-schizophrenic control. The age group of the patient was between 15 and 45 years and the male female ratio was 2.7:1. Serum concentration of glutamate (598.83 +/- 574.48 nmol/ml) was significantly higher (p < 0.001) in schizophrenic group compared to control (196.16 +/- 171.31 nmol/ ml). The serum asparate concentration was also significantly higher in schizophrenic cases (282.91 +/- 299.94 nmol/ml) as compared to control (33.89 +/- 42.68 nmol/ml, p < 0.001). The correlation coefficient between serum glutamate and asparate was significant (p < 0.001). The increased serum glutamate and asparate levels may be the causative or contributing factor in the pathogenesis and progression of schizophrenia.

Effects of taurine on early changes of excitatory amino acids in rabbit brain due to deep hypothermic circulatory arrest / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effects of taurine (Tau) on early changes of excitatory amino acids (EAA) in hippocampus rabbit brain due to deep hypothermic circulatory arrest (DHCA).</p><p><b>METHODS</b>Sixteen New Zealand rabbits were randomly allocated into 2 groups: Tau 150 mg/kg group (group I, n = 8), control group (group II, n = 8). Cardiac pulmonary bypass (CPB) was set up after cerebral microdialysis model was established. High performance liquid chromatography was employed to monitor the continuous changes of glutamic acid (Glu), aspartic acid (Asp), Tau and glycine (Gly) in the hippocampus CA1 region at anaesthesia periods, CPB stage, pre 30 minutes in DHCA, post 30 minutes in DHCA, pre 30 minutes in rewarming, post 30 minutes in rewarming.</p><p><b>RESULTS</b>The increase of Glu in group II was (5.1 +/- 1.5) and (4.1 +/- 1.4) times higher than that at anaesthesia periods (t = 3.74, 5.45, P < 0.01), and the increase of Glu in group I was (2.1 +/- 1.5) and (1.1 +/- 0.4) times than that at anaesthesia periods at pre 30 minutes and post 30 minutes rewarming stage respectively. Rising of Gly in group II was 6.7 (3.6, 13.6) times than that at anaesthesia periods (T = 75.00, P < 0.05), the rising of Gly in group I was 4.2 (3.8, 11.5) times at post 30 minutes in DHCA. Rising of Tau in group I was 6.9 (3.0, 14.2) and 10.6 (2.8, 22.5) times than that at anaesthesia periods (T = 75.00, P < 0.05 and T = 90.00, P < 0.05) and rising of Tau in group II was 4.0 (3.0, 5.7) and 3.2 (1.2, 7.6) times than that at anaesthesia periods at post 30 minutes in DHCA and pre 30 minutes rewarming stage respectively. Asp was no evident change at every periods.</p><p><b>CONCLUSION</b>DHCA might increase the excitatory amino acids in the early phases of circulatory restoration. Exterior Tau 150 mg/kg could inhibit release of EAA.</p>

Experimental study of traditional Chinese medicine in the treatment of vascular dementia / 中国中药杂志

To explore the new progress of the experimental study of traditional Chinese medicine in the treatment of vascular. Consulted the relevant papers and integrated the elementary theory, we summarized the virtue of Chinese medicine in the treatment of vascular dementia and insufficient and future development of the experimental study of it. It was confirmed that the traditional Chinese medicine has a lot of target spots in the brain and less ill-effect, it could ameliorate several phenotypes of pathophysiology of vascular dementia and improve the ability of learning and memory of animals with vascular dementia.

The Effects of Intrathecal Ketamine and NBQX on Neurologic Injury and Spinal Cord Glutamate Receptor mRNA Expression in Transient Spinal Ischemia in the Rat / 대한구급학회지

BACKGROUND: Spinal cord injury occurring as the result of surgical repair of thoracic and thoracoabdominal aortic disease remains a devastating complication. Excitatory amino acids have been known to cause neurologic injury after neuronal ischemia. The purpose of this study was to elucidate the effects of intrathecal ketamine or NBQX on neurologic outcome and NMDA receptor gene expression in transient spinal ischemia. METHODS: Sprague-Dawley rats were anesthetized with enflurane, divided by 4 groups: Control (C group), Intrathecal ketamine 0.1 mg (K-1 group), Intrathecal ketamine 0.2 mg (K-2 group), and intrathecal NBQX 1 nM (N group). Spinal ischemia was produced by both induced hypotension and thoracic aortic cross clamping. After spinal ischemia, neurologic scores were assessed after 1, 2, 3 hours. After 3 hours rats were euthenized and spinal cords were removed for the assay of NMDAR and mGlu1 mRNA. RESULTS: The neurol ogic scores of K-2 and N groups were significantly lower than C group and K-1 group. There were no significant difference between K-1 group and C group. The NMDAR and mGlu1 gene expression was increase in C and K-1 group compared to sham operation. In K-2 and N groups, the gene expressions were significantly lesser than C group. CONCLUSIONS: The NMDAR and mGlu1 gene expressions were increased in transient spinal ischemia. Intrathecal ketamine and NBQX were effective in preventing neurologic injury after transient spinal ischemia. The NMDA antagonistic action of ketamine might involve to prevent neurologic injury.

Investigation of central mechanism of insulin induced hypoglycemic convulsions in mice.

Insulin produces seizures in healthy and diabetic animals. Amongst suggested mechanisms, the role of neuromodulators and neurotransmitters is not clear. The present study explores the mechanisms involved in insulin-induced convulsions. Convulsions were induced in Swiss male albino mice with graded doses of insulin. Blood sugar levels were measured prior to and after the first convulsion. Drugs like 5-HTP (5-HT precursor), pCPA (5-HT depletor), ondansetron (5-HT3 antagonist), ketanserin (5-HT, antagonist), ketamine (NMDA antagonist), 1-dopa (dopamine precursor) and reserpine (amine depletor) were studied for interaction with convulsive behaviour induced by insulin. Insulin in 2 IU/kg dose did not produce convulsions while 4 and 8 IU/kg doses produced convulsions in 50% and 100% of animals respectively. 5-HTP, ondansetron, ketanserin, ketamine and l-dopa significantly protected/inhibited animals from convulsions at all studied doses of insulin. On the contrary, pCPA and reserpine potentiated insulin induced convulsions. Insulin caused mortality in 40 and 100% animals with 4 and 8 IU/kg doses respectively. pCPA and reserpine treatments caused mortality at all doses of insulin, while other drugs did not influence insulin induced mortality. Blood sugar levels were reduced in all groups irrespective of the presence or absence of convulsions. A definitive link of serotonergic, dopaminergic and excitatory amino acid pathways in mediating insulin-induced hypoglycemic convulsions is suggested.