Excitatory amino acid changes in the brains of rhesus monkeys following selective cerebral deep hypothermia and blood flow occlusion

Selective cerebral deep hypothermia and blood flow occlusion can enhance brain tolerance to ischemia and hypoxia and reduce cardiopulmonary complications in monkeys. Excitotoxicity induced by the release of a large amount of excitatory amino acids after cerebral ischemia is the major mechanism underlying ischemic brain injury and nerve cell death. In the present study, we used selective cerebral deep hypothermia and blood flow occlusion to block the bilateral common carotid arteries and/or bilateral vertebral arteries in rhesus monkey, followed by reperfusion using Ringer＇s solution at 4~C. Microdialysis and transmission electron microscope results showed that selective cerebral deep hypothermia and blood flow occlusion inhibited the release of glutamic acid into the extracellular fluid in the brain frontal lobe and relieved pathological injury in terms of the ultrastructure of brain tissues after severe cerebral ischemia. These findings indicate that cerebral deep hypothermia and blood flow occlusion can inhibit cytotoxic effects and attenuate ischemic/ hypoxic brain injury through decreasing the release of excitatory amino acids, such as glutamic acid.

Inhibitory and excitatory amino acids in the cerebrospinal fluid of children with two types of cerebral palsy

BACKGROUND： Under normal conditions, excitatory amino acids are dynamically balanced with inhibitory amino acids. Excitatory amino acids have been implicated in perinatal brain injury. OBJECTIVE： To investigate differences in the levels of the excitatory amino acids glutamic acid and aspartic acid, and the inhibitory amino acid gamma-aminobutyric acid （GABA） in the cerebrospinal fluid （CSF） of children with spastic cerebral palsy or athetotic cerebral palsy. DESIGN, TIME AND SETTING： Case-control exploratory observation of neurotransmitter in patients. The experiment was performed in the Pediatrics Department of the Second Affiliated Hospital of Changsha Medical College, the Cerebral Palsy Center of Xiangtan Affiliated Hospital of South China University and the Pediatrics Department of Xiangya Hospital, between February 2006 and May 2007. PARTICIPANTS： We selected 27 children with cerebral palsy, including 13 with spastic cerebral palsy and 14 with athetotic cerebral palsy. We selected 10 patients who were not affected by any neurological disease as controls. METHODS： Two mL blood-free CSF was harvested between the third and fourth lumbar vertebrae of each patient after anesthesia, and stored at -70℃. One mL CSF was mixed with 10 mg sulfosalicylic acid and placed in ice-bath for 10 minutes, then centrifuged 2 000 g for 10 minutes. The supernatant was collected for amino acid quantitation. MAIN OUTCOME MEASURES： The concentrations of glutamic acid, aspartic acid and GABA in the CSF were determined by high-performance liquid chromatography and fluorometric method. The correlation of glutamic acid, aspartic acid and GABA levels with muscular tension in children with cerebral palsy was analyzed using linear dependence. RESULTS： The concentration of GABA was significantly lower in both spastic cerebral palsy and athetotic cerebral palsy patients than in the control group （P 〈 0.01）. Glutamic acid and aspartic acid were significantly higher in both cerebral palsy groups than in the control group （P 〈 0.05-0.01）. The concentration of GABA was significantly decreased in spastic cerebral palsy patients compared with the athetotic cerebral palsy group （P 〈 0.05）. Muscular tension was positively correlated with the concentration of glutamic acid in spastic cerebral palsy patients （P 〈 0.05） but there was no significant correlation between aspartic acid or GABA and muscular tension （P 〉 0.05）. CONCLUSION： Spastic cerebral palsy and athetotic cerebral palsy patients exhibit an imbalance of excitatory amino acids and inhibitory amino acids in their CSF： an increase in glutamic acid and aspartic acid, and a decrease in GABA. Amino acid levels are different in the CSF in varied types of cerebral palsy.

Alteration of Excitatory Amino Acid in Experimen-tal Spinal Cord Injury in Rats

Objective To detect the effect of excitatory ammo add (EAA) in the secondary damage following spinal cord injury (SCI). Methods Glutamate (Glu) and Aspartate (Asp) on the injury site (T8) were studied using a rat SCI model induced by Allen's weight drop method (10g×2. 5cm). The result suggested that Asp and Glu were significantly increased in 10 mm. Results Glu was significantly decreased from 2 h to 24 h,while Asp was a tittle reduced in 2 h,and slightly rose in 4 h as compared with Control Group. Though elevated in 8 h,it dropped again in 24h as compared with Control Group. Conclusion The result indicates that the rise of EAA following SCI could be the cause of the secondary spinal cord damage.

Effect of topiramate on partial excitatory amino acids in hippocampal dentate gyrus of rats after alcohol withdrawal

BACKGROUND： Many researches have indicated that the imbalances of various amino acid transmitters and neurotransmitters in brain are involved in the formation of alcohol withdrawal, especially that glutamic acid is one of the important transmitters for alcohol tolerance in central nervous system. OBJECTIVE： To observe the changes of excitatory amino acids in hippocampal dentate gyrus in rats with long-term alcohol drinking after withdrawal under consciousness, and investigate the therapeutic effect of topiramate on alcohol withdrawal. DESIGN ： A randomized control animal experiment SETTING ： Department of Neurology, Affiliated Hospital of Yanbian University MATERIALS： Thirty male Wistar rats of 4 months old, weighing 300-350 g, were purchased from the Experimental Animal Department, Medical College of Yanbian University. Topiramate was produced by Swish Cilag Company, and the batch number was 02CS063. METHODS： The experiments were carried out in the Department of Physiology, Medical College of Yanbian University from August 2005 to February 2006. ① The rats were divided randomly into three groups： control group （n=10）, alcohol group （n=10） and topiramate-treated group （n=10）. Rats in the alcohol group and topiramate-treated group were given intragastric perfusion of 500 g/L alcohol （10 mL/kg）, once a day for 4 weeks successively, and then those in the topiramate-treated group were treated with 80 mg/kg topiramate at 24 hours after the last perfusion of alcohol, once a day for 3 days successively. Rats in the control group were intragastricly given isovolume saline. ② The withdrawal symptoms were assessed at 6, 30, 48 and 72 hours after the last perfusion of alcohol by using the withdrawal rating scale set by Erden et al, which had four observational indexes of stereotyped behaviors, agitation, tail stiffness and abnormal posture, each index was scored by 5 points, the higher the score, the more obvious the symptoms. ③ The contents of aspartic acid and glutamic acid in hippocampal dentate gyrus were detected with microdialysis technique and high-performance liquid chromatograpy （HPLC） respectively at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the three groups. MAIN OUTCOME MEASURES ： ① Scoring results of alcohol withdrawal symptoms; ② Changes of the contents of aspartic acid and glutamic acid in hippocampal dentate gyrus at the alcohol withdrawal symptoms, and the effects of topiramate. RESULTS： Seven rats were excluded due to inaccurate localization and natural death, and 23 rats were involved in the analysis of results. ①In the alcohol group, the scores of alcohol withdrawal symptoms at 30 and 48 hours after the last perfusion of alcohol were obviously higher than those in the control group （10.50±0.96, 14.17±1.25; 3.50±0.92, 3.16±0,31; P 〈 0.01）. In the topiramate-treated group, the scores at 30 hours after the last perfusion of alcohol （6.06±0.82, 3.50±0.92, P 〈 0.05）, and the withdrawal scores at 48 and 72 hours were close to those in the control group （4.57±0.58, 3.30±0.71; 3.16±0.31, 3.66±0.67; P 〉 0.05）.② Changes of the contents of glutamic acid in hippocampal dentate gyrus： In the alcohol group, the content of glutamic acid at 48 hours after the last perfusion of alcohol was significantly increased as compared with that at 6 hours [（143.32±11.42）%, （99.12±0.69）%; P 〈 0.05], and that at 72 hours was close to that at 6 hours [（78.50±16.40）%, （99.12±0.69）%; P 〉 0.05]. The contents of glutamic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [（100.30±0.37）%, （118.91±10.40）%, （99.55±12.81）%, （99.08±11.42）%; P 〉 0.05], The content of glutamic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group （P 〈 0.05）, and those at 30 and 72 hours were close （P 〉 0.05）. ③ Changes of the contents of aspartic acid in hippocampal dentate gyrus： In the alcohol group, the contents of aspartic acid at 30 and 48 hours after the last perfusion of alcohol were significantly increased as compared with that at 6 hours [（126.60±8.67）%, （129.17±10.40）%, （99.25±0.87）%; P 〈 0.05], and that at 72 hours was close to that at 6 hours [（89.87±9.93）%, （99.25±0.87）%; P 〉 0.05]. The contents of aspartic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [（100.27±0.32）%, （120.81 ±12.63）%, （98.91±7.83）%, （85.92±8.07）%; P 〉 0.05]. The content of aspartic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group （P 〈 0.05）, and those at 30 and 72 hours were close （P 〉 0.05）. CONCLUSION： ① The occurrences of alcohol withdrawal symptoms are correlated with the increased contents of excitatory amino acids in hippocampal dentate gyrus in rats. ② Topiramate can alleviate the alcohol withdrawal symptoms, which may be correlated with the decreased contents of excitatory amino acids in hippocampal dentate gyrus in rats.

Effects of Nerve Growth Factor on Excitatory Amino Acid Content in Spinal Cord Neuron after Spinal Cord Injury

To investigate the protective mechanism of nerve growth factor (NGF) on spinal cord injury (SCI), surgical spinal cord injury in Wistar rats was performed by a 10 g2.5 cm impact on the posterior spinal cord at T8 level, and a thin plastic tube was placed in subarachoid space below the injury level for perfusion of solution. To the experimental animals were given 60 g (20 l liquid) NGF, purified from bovine seminal plasma, at the moment of injury and 1,2,3,4,8,12,24 h after injury. An equal volume of normal saline was given to rats of the control group at the same time. In the expermental group, the injured spinal cord tissue was taken following treatment. The contents of the excitatory amino acids (Glu, Asp) were determined by high performance liquid chromatography (HPLC). Excitatory amino acid contents in the injured spinal cord were significantly increased at 10 min and 8 h after the injury as compared with those in the control group. However, The peak values of the excitatory amino acid contents in NGF group were obviously lowered. NGF might protect spinal cord against injury in vivo. One of the possible mechanisms is that NGF prohibits neurotoxicity of the exitatory amino acids.

Effect of Zhongfeng Naodeping Granule on Hippocampal Excitatory Amino Acid and Neuron of Stroke-Prone Spontaneously Hypertensive Rats with Hemorrhagic Apoplexy

Objective: To observe the effects ofZhongfeng Naodeping Granule (ZFNDPG) onhemorrhagic apoplexy. Methods: The strokeprone spontaneously hypertensive rats(SHRsp ) were used to study effects ofZFNDPG on hemorrhage apoplexy. Excitatoryamino acid (EAA) concentration in hippocampus sector, neuronal density and ultrastructural changes in hippocampal CAI sector weremeasured. Results: In pathological modelgroup glutamate (Gin) and aspartate (Asp)concentration elevated obviously. With theZFNDPG treating SHRsp of hemorrhagicapoplexy, Gin and Asp concentration in hippocampal sector could be markedly inhibited,compared with model group, P < 0.05-0. 01. Neuronal morphology was observed:neurone injury was mild and neuronal densityincreased in hippocampal CA1 sector of treatment group, compared with model group, P< 0. 01. Electron microscopy showed t edema,degeneration and necrosis caused by hemorrhagic apoplexy were improved after theZFNDPG treatment. Conclusions: Effects ofprotecting neurone for SHRsp on hemorrhagicapoplexy might be associated with thatZFNDPG inhibited concentration of EAA.

Effect of Diazepam on the Contents of Amino Acids and Free Radical during Ischemia/Reperfusion Injury

The protective effect and mechanism of diazepam on ischemia neurons during cerebral ischemia and reperfusion were studied. Sixty three Wistar rats were divided randomly into nine groups: control group , ischemia groups including subgroups of is3h, is3 h/rep1 h, is3 h/rep2 h, is3 h/rep3 h, diazepam treated groups , including subgroups of is3 h, is3 h/rep1 h, is3 h/rep2 h, is3 h/rep3 h with Zea longa's animal model of middle cerebral artery occlusion. The comparison between the ischemia group and diazepam treated group showed that diazepam could obviously decrease the production of glutamate, asparate, MDA and increase the synthesis and release of GABA, SOD and GSH PX. It was concluded that diazepam exerted its protective effects on neurons through complex mechanisms of regulating the synthesis and release of excitotary/inhibitory amino acids and free radicals.

Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry

Aconitine,a common and main toxic component of Aconitum,is toxic to the central nervous system.However,the mechanism of aconitine neurotoxicity is not yet clear.In this work,we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine.HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system.Meanwhile,to confirm the metabolic mechanism of aconitine toxicity on HT22 cells,the levels of lactate dehydrogenase,intracellular Ca^(2+),reactive oxygen species,glutathione and superoxide dismutase,and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology.Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid,which was followed by the accumulation of lactic acid and reduction of glucose.The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca^(2+)overload and oxidative stress,and eventually result in cell apoptosis.In general,we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.

Acupuncture Effects on Levels of Excitatory AminoAcids in Brain of SAM-P/8

Objective: To reveal the central mechanism of acupuncture on the central nervous system.Methods: Excitatory amino acids (EAAs) were determined in cerebral cortex, hippocampus and striate body ofleft side by Shimadzu LC-6A HPLC. Results: Metabolic disorder existed in excitatory amino acids: The contentof Gin, Gin, Asp and Asn in hippocampus and striate body were generally increased (P < 0. 05, or P < 0. 01 ),the content of Asn in cerebral cortex was also increased (P < 0. 01 ). The changes of inhibited amino acids (I-AAs) to certain extent also existed in the three regions but without regularity. Xingnao Kaiqiao (醒脑开窍)acupuncture method could obviously reduce the levels of Gin, Asp, Gin and Asn in hippocampus and striate bodyand the levels of Asn and Gin in cerebral cortex of senescence accelerate mouse P/8 (SAM-P/8). The non-acuPOint acupuncture method did not exert obvious effects on Gln and Asp which was quite different from XingnaoKaiqiao acupuncture effects. Conclusions: (1 ) The hyperrnetabolism of EAAs existed in the brain of SAM-P/8,which could be regarded as the imPOrtant pathological mechanism of disorder in study and memory and cerebralatrophy. (2) Xingnao Kaiqiao acupuncture method could obviously regulate the abnormal metabolism of cerebralEAAs, which could be regarded as one of the mechanisms of acupuncture effects on improving brain function.(3) Acupuncture effect has remarkable specificity of acupoint.

Gabapentin inhibits central sensitization during migraine

Peripheral and central sensitizations are phenomena that occur during migraine. The role of gabapentin, a migraine preventive drug, on central sensitization remains unclear. In this study, a rat model of migraine was established by electrical stimulation of the trigeminal ganglion, and the animals were given intragastric gabapentin. Changes in amino acid content in the cerebrospinal fluid and protein kinase C membrane translocation in the spinal trigeminal nucleus were examined to clarify the mechanisms underlying the efficacy of gabapentin in the treatment of central sensiti- zation during migraine. Electrophysiology, liquid chromatography-mass spectrometry and western blot analysis results revealed that gabapentin reduces neuronal excitability in the spinal nucleus in the trigeminal nerve, decreases excitatory amino acid content and inhibits the activation of protein kinase C. This provides evidence that excitatory amino acids and protein kinase C are involved in the formation and maintenance of central sensitization during migraine. Gabapentin inhibits mi- graine by reducing excitatory amino acid content in the cerebrospinal fluid and inhibiting protein kinase C activation.

Neuroprotective effect of penehyclidine hydrochloride on focal cerebral ischemia-reperfusion injury

Penehyclidine hydrochloride can promote microcirculation and reduce vascular permeability. However, the role of penehyclidine hydrochlodde in cerebral ischemia-reperfusion injury remains unclear. In this study, in vivo middle cerebral artery occlusion models were established in experimental rats, and penehyclidine hydrochloride pretreatment was given via intravenous injection prior to model establishment. Tetrazolium chloride, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and immunohistochemical staining showed that, penehyclidine hydrochloride pretreatment markedly attenuated neuronal histopathological changes in the cortex, hippocampus and striatum, reduced infarction size, increased the expression level of BcI-2, decreased the expression level of caspase-3, and inhibited neuronal apoptosis in rats with cerebral ischemia-reperfusion injury. Xanthine oxidase and thiobarbituric acid chromogenic results showed that penehyclidine hydrochloride upregulated the activity of superoxide dismutase and downregulated the concentration of malondialdehyde in the ischemic cerebral cortex and hippocampus, as well as reduced the concentration of extracellular excitatory amino acids in rats with cerebral ischemia-reperfusion injury. In addition, penehyclidine hydrochloride inhibited the expression level of the NR1 subunit in hippocampal nerve cells in vitro following oxygen-glucose deprivation, as detected by PCR. Experimental findings indicate that penehyclidine hydrochloride attenuates neuronal apoptosis and oxidative stress injury after focal cerebral ischemia-reperfusion, thus exerting a neuroprotective effect.

Changes in neuronal apoptosis and apoptosis modulatory factors in cerebral ischemia/reperfusion

BACKGROUND： The high concentration of glutamate release is the main cause for neuronal cell death. The relationship between glutamate level and apoptosis during ischemia/reperfusion injury is still unclear. OBJECTIVE： To observe the neuronal apoptosis at 24 and 72 hours following cerebral ischemia/reperfusion in rats, and analyze the possible influencing factors. DESIGN： A randomized controlled animal experiment. SETTING： School of Medicine, Southern Yangtze University. MATERIALS： Totally 30 male adult Sprague Dawley （SD） rats of clean grade, weighing 240 - 290 g, were obtained from Shanghai Experimental Animal Center, Chinese Academy of Sciences. The rats were randomly divided into sham-operated group （n=10） and model group （n=20）. Each group was observed at 24 and 72 hours after ischemia/reperfusion, 5 rats at each time point in the sham-operated group, whereas 12 at 24 hours and 8 at 72 hours in the model group. Kits for determining apoptosis and Bcl-2 were bought from Wuhan Boster Biological Technology, Co., Ltd.; Kit for calcineurin from Nanjing Jiancheng Bioengineering Institute. METHODS： The experiment was carried out in the Functional Scientific Research Room of Southern Yangtze University from June to October in 2006.①Right middle cerebral artery was occluded by inserting a thread through internal carotid artery （ICA）. The surgical process for the sham-operated rats was the same as that in the model group except a nylon suture inserted the ICA. According to Longa five-degree standard, the neurological deficit evaluation of rats was evaluated after surgery, and grades 1 - 3 were taken as successful model establishment. The blood was recirculated by withdrawing the nylon filament under anesthesia at 2 hours after ischemia in successful rat models. ②After reperfusion, the brain tissue was quickly removed at 24 or 72 hours and the slices were obtained from optic chiasma to funnel manubrium. The changes of the number of apoptotic cells were observed using the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling method. The expressions of Bcl-2 protein were determined with immunohistochemical staining. The activity of calcineurin was determined by the inorganic phosphorus method. The content of excitatory amino acid was detected by high performance liquid chromatography. MAIN OUTCOME MEASURES： ①Glutanate content in brain tissue; ② Conditions of apoptosis; ③Calcineurin activity in brain tissue; ④ Bcl-2 expression in brain tissue. RESULTS： Totally 30 SD rats were used, 5 died and the other 25 were involved in the analysis of results. ① Changes of apoptosis： There were 0 - 3 apoptotic cells in the sham-operated group. In the model group, the numbers of apoptotic cells were obviously increased at 24 and 72 hours of reperfusion （P 〈 0.01 ）, and it was markedly reduced at 72 hours as compared with 24 hours （P 〈 0.0l）. ② Changes of glutanate content： The glutamate contents at 24 and 72 hours of repeffusion in the model group were obviously higher than those in the sham-operated group （P 〈 0.01）; In the model group, it was obviously increased at 24 hours as compared with 72 hours （P 〈0.01）. ③ Changes of Bcl-2 protein： In the model group, the Bcl-2 protein expression had no obvious changes at 24 hours of reperfusion, and it was obviously enhanced at 72 hours, which was obviously different from that in the sham-operated group and that at 24 hours （P 〈 0.0l）. ④Changes of calcinerin activity： In the model group, the activity of calcineurin in brain tissue had no obvious changes at 24 hours of reperfusion; The activity of calcineurin at 72 hours was obviously higher than that in the sham-operated group and that at 24 hours （P 〈 0.01）. CONCLUSION： The brain cyto-apoptosis action at different time points following reperfusion incompletely depends on the glutamate levels, while it depends on the interaction of some apoptosis related factors, such as amino acid, calcineurin, and Bcl-2, etc.

Molecular chaperones and hypoxic-ischemic encephalopathy

Hypoxic-ischemic encephalopathy（HIE） is a disease that occurs when the brain is subjected to hypoxia,resulting in neuronal death and neurological deficits,with a poor prognosis.The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release,cellular proteolysis,reactive oxygen species generation,nitric oxide synthesis,and inflammation.The molecular and cellular changes in HIE include protein misfolding,aggregation,and destruction of organelles.The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway,the extrinsic Fas receptor pathway,and the endoplasmic reticulum stress-induced pathway.Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century.Hypothermia,xenon gas treatment,the use of melatonin and erythropoietin,and hypoxic-ischemic preconditioning have proven effective in HIE patients.Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes.A large number of molecular chaperones are induced after brain ischemia and hypoxia,among which the heat shock proteins are the most important.Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects.Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations,assisting in the proper folding of newly synthesized polypeptides,regulating the degradation of misfolded proteins,inhibiting the aggregation of proteins,and by controlling the refolding of misfolded proteins.In addition,heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways,including the intrinsic pathway,the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway.Molecular chaperones play a key role in neuroprotection in HIE.In this review,we provide an overview of the mechanisms of HIE and discuss the various treatment strategies.Given their critical role in the disease,molecular chaperones are promising therapeutic targets for HIE.

Expression of multiple glutamate transporter splice variants in the rodent testis

Glutamate is a regulated molecule in the mammalian testis. Extracellular regulation of glutamate in the body is determined largely by the expression of plasmalemmal glutamate transporters. We have examined by PCR, western blotting and immunocytochemistry the expression of a panel of sodium-dependent plasmalemmal glutamate transporters in the rat testis. Proteins examined included： glutamate aspartate transporter （GLAST）, glutamate transporter 1 （GLT1）, excitatory amino acid carrier 1 （EAAC1）, excitatory amino acid transporter 4 （EAAT4） and EAAT5. We demonstrate that many of the glutamate transporters in the testis are alternately spliced. GLAST is present as exon-3- and exon-9-skipping forms. GLT1 was similarly present as the alternately spliced forms GLT1 b and GLTlc, whereas the abundant brain form （GLTla） was detectable only at the mRNA level. EAAT5 was also strongly expressed, whereas EAAC1 and EAAT4 were absent. These patterns of expression were compared with the patterns of endogenous glutamate localization and with patterns of D-aspartate accumulation, as assessed by immunocytochemistry. The presence of multiple glutamate transporters in the testis, including unusually spliced forms, suggests that glutamate homeostasis may be critical in this organ. The apparent presence of many of these transporters in the testis and sperm may indicate a need for glutamate transport by such cells.

Dynamic expression of cerebral cortex and hippocampal glutamate transporters in a rat model of chest compression-induced global cerebral ischemia

The present study established a rat model of global cerebral ischemia induced by chest compression for six minutes to dynamically observe expressional changes of three glutamate transporters in the cerebral cortex and hippocampus. After 24 hours of ischemia, expression of glutamate transporter-1 significantly decreased in the cerebral cortex and hippocampus, which was accompanied by neuronal necrosis. At 7 days post-ischemia, expression of excitatory amino acid carrier 1 decreased in the hippocampal CA1 region and cortex, and was accompanied by apoptosis Expression of glutamate-aspartate transporter remained unchanged at 6 hours 7 days after ischemia. These results suggested that glutamate transporter levels were altered at different periods of cerebral ischemia.