Changes Of Excitatory Amino Acids Research Articles

Effect of dexmedetomidine on the changes of EAA and the expression of NMDA NR1 protein in hippocampus in global cerebral ischemia/reperfusion rats

To observe the effects of dexmedetomidine (DEX) on glutamate (Glu), aspartic acid (Asp) release and NMDAR1 expression in hippocampus in global cerebral ischemia/reperfusion rats, and investigate the protective effect and the related mechanism of neurotransmitters. Fifty-four male Wistar rats were randomly divided into three groups (n=18):sham group(A), ischemia/reperfusion group(B), dexmedetomidine pretreatment group(C). Total cerebral ischemia model was set up by four vessel occlusion in rats. Glu and Asp levels were measured with microdialysis at different time. Then the animals were decapitated and the brains were immediately removed to detect NMDAR1 expression in hippocampus area by immunohistochemistry and Western-blot. Compared with that in group B, the levels of Glu, Asp and NMDA NR1 protein were significantly decreased in the dexmedetomidine pretreatment group (P<0.05 or 0.01). Dexmedetomidine might has a protective effect on hippocampus in global cerebral ischemia/reperfusion animals. The protective mechanism might be involved in inhibiting excitatory amino acids(EAA) release and NMDAR1 expression.

Effect of polydatin on dynamic changes of excitatory amino acids in cerebrospinal fluid of cerebral hemorrhage rats

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. 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. 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. 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.

Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee in rats: role of excitatory amino acids

Our present study examined the effect of intra-articular cyclooxygenase-2 (COX-2) inhibitor parecoxib on osteoarthritis (OA) progression and the concomitant changes in excitatory amino acids' (EAAs) levels of the anterior cruciate ligament-transected (ACLT) knee joint dialysates. OA was induced in Wistar rats by anterior cruciate ligament transection of the knee of one hindlimb, the other was left unoperated and untreated. Rats were placed into four groups: Group ACLT/P received intra-articular parecoxib injection (100 microg) in the ACLT knee once a week for 5 consecutive weeks starting at 8 weeks after surgery. Group ACLT/S received the same procedure as group ACLT/P with saline injection instead. Naïve (Naïve/P) rats received only intra-articular parecoxib injection in one knee once a week for 5 consecutive weeks without surgery. The sham-operated rats underwent arthrotomy only without treatment. Twenty weeks after surgery, knee joint dialysates were collected and EAAs' concentration was assayed by high-performance liquid chromatography, and gross morphology and histopathology (Mankin and synovitis grading) were examined on the medial femoral condyles and synovia. Parecoxib alone had no effect on cartilage and synovium of normal knees in Naïve/P rats. In ACLT/P rats, parecoxib treatment showed a significant inhibition of cartilage degeneration of the medial femoral condyle at both the macroscopic level (1.15+/-0.17 vs 2.55+/-0.12, P<0.05) and the Mankin scores (3.03+/-0.28 vs 8.82+/-0.43, P<0.05). Intra-articular parecoxib injection also suppressed the synovial inflammation of ACLT joint compared to the ACLT/S group (3.92+/-0.41 vs 9.25+/-0.32, P<0.05). Moreover, glutamate and aspartate levels were also significantly reduced in the ACLT/P group compared to the ACLT/S group by parecoxib treatment (91.2+/-9.4% vs 189.5+/-17.0%, P<0.05 and 98.2+/-11.6% vs 175.3+/-12.4%, P<0.05, respectively). This study shows that intra-articular injection of COX-2 inhibitor parecoxib inhibits the ACLT-induced OA progression; it was accompanied by a reduction of glutamate and aspartate concentration in the ACLT joint dialysates. From our present results, we suggested that intra-articular parecoxib injection, in addition to the anti-inflammatory effect, inhibiting the EAAs' release, may also play a role in inhibiting the traumatic knee injury induced OA progression.

Effects of taurine on early changes of excitatory amino acids in rabbit brain due to deep hypothermic circulatory arrest

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). 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. 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. DHCA might increase the excitatory amino acids in the early phases of circulatory restoration. Exterior Tau 150 mg/kg could inhibit release of EAA.

Relationship between cerebral interstitial levels of amino acids and phosphorylation potential during secondary energy failure in hypoxic-ischemic newborn piglets.

The aim of this study was to determine the validity of the hypothesis that excitatory amino acids are related to phosphorylation potential during primary and secondary cerebral energy failure observed in asphyxiated infants. We report here the results of experiments using newborn piglets subjected to severe transient cerebral hypoxia-ischemia followed by resuscitation. We examined cerebral energy metabolism by phosphorus nuclear magnetic resonance spectroscopy and changes in levels of amino acid neurotransmitters in the cortex by microdialysis before, during, and up to 24 h after the hypoxic-ischemic insult. The concentrations of aspartate, glutamate, taurine, and gamma-aminobutyric acid were significantly elevated during the hypoxic-ischemic insult compared with prebaseline values. Shortly after resuscitation, glutamate, taurine, and gamma-aminobutyric acid concentrations decreased but then began to increase again. These secondary elevations were greater than the primary elevations. A negative linear correlation was found between primary interstitial levels of glutamate and taurine and minimum values of phosphocreatine/inorganic phosphate during the secondary energy failure. The cerebral energy state depended on the time course of changes in excitatory amino acids, suggesting that amino acids play distinct roles during the early and delayed phases of injury.

Neurophysiological and Clinical Aspects of Glucocorticoids and Memory: A Review

Neuropsychologists are increasingly involved in the assessment and treatment of individuals with glucocorticoid (GC) dysfunction. This review examines the clinical and neurophysiological changes associated with alterations in GC levels, with specific emphasis on changes in hippocampal plasticity and memory impairments. Hypothalamic-pituitary-adrenal (HPA) axis regulation of GC production and GC effects at hippocampal receptors are examined. GC-related changes in memory and hippocampal plasticity are considered in a wide array of populations, including animals, healthy adults, patients receiving exogenous GC treatments, and patients with neuropsychiatric disorders resulting in GC dysregulation. Hypotheses regarding GC-related memory changes are considered, with emphasis on hippocampal neurotoxicity and changes in excitatory amino acids, glucose metabolism and neurotrophic factors. These hypotheses are examined, with special attention given to inconsistencies and contradictions within this body of research. Finally, implications for neuropsychological evaluation and future research are presented.

Excitatory Amino Acids in Cerebrospinal Fluid of Patients with Acute Head Injuries

The excitatory amino acids (EAAs) glutamate (Glu) and aspartate (Asp) play a role in the pathogenesis of postischemic and posttraumatic brain insult. The changes of EAAs in cerebrospinal fluid (CSF) of patients with traumatic brain injury are incompletely understood. We used reversed-phase HPLC with precolumn derivatization with o-phthalaldehyde and fluorescence detection to measure Glu and Asp in CSF of 42 patients with acute head injury and 9 control adults without neurologic diseases. We assessed the Glasgow Coma Scale (GCS) on admission, the main lesion patterns on computed tomography (CT) scan within 24 h post trauma, and the Glasgow Outcome Scale (GOS) 3 months post injury. The mean concentrations of Glu and Asp in CSF in the brain-injured group were significantly higher than those of the control group (Glu, P <0.001; Asp, P <0.05). In patients admitted within 24 h after severe injury (n = 13), peak Glu values appeared within 48 h in 11 patients (85%), and the mean value remained higher than control values at day 7 (P <0.02). The concentrations of EAAs were higher in patients with severe injuries (GCS < or =8) than in those with milder injuries (Glu, P <0.001; Asp, P <0.05). GCS and peak EAAs correlated negatively (Glu, rs = -0.5706, P <0.001; Asp, rs = -0.5503, P <0.001). The patients with focal brain contusion on initial CT scan (n = 8) had a significantly lower peak Glu value than the patients with other patterns (n = 8-15; P <0.02 to 0.001). The peak value of EAAs in the poor-outcome group (including severe disability, vegetative state, and death) was significantly higher than in the good-outcome group (good recovery and moderate disability; Glu, P <0.001; Asp, P <0.01); GOS was closely correlated to the EAA values (Glu, rs = 0.5737, P <0.001; Asp, rs = 0.5470, P <0.001). The EAA concentrations in CSF increase after acute head injury and remain higher for at least 1 week post injury in severely injured patients. The more severe the trauma, the more obvious the excitotoxicity induced by EAAs and the worse the outcome.

Changes of amino acid levels and aspartate distribution in the cervical spinal cord after traumatic spinal cord injury.

To evaluate the role of excitatory amino acids in secondary injury occurring after spinal cord trauma, several experimental studies focusing on the the changes of amino acid levels in the spinal cord have been performed to date. However, because of technical limitations, it has not been possible to correlate the local changes of excitatory amino acids with the total tissue levels of excitatory amino acids. To investigate the connection between the spread of injury and the excitatory amino acids, we assessed, the local changes of aspartate through novel experimental approaches like immunoreactivity via fluorescence microphotometry and histopathology while also analyzing the total tissue levels of amino acids via HPLC. These studies were performed using a model of incomplete cervical spinal cord injury in rats. Through this approach, we found that the levels of excitatory amino acids, such as glutamate and aspartate, began to decrease immediately after injury. No significant decrease was observed in the other amino acids. Similarly, local changes in aspartate in the spinal cord were observed using fluorescence microphotometry. The decrease in the anterior and posterior horns was rapid up to 15 min after injury, but, slowed thereafter, suggesting that a release of excitatory amino acids occurred at the site of primary injury almost immediately following injury. At 15-min post-injury large neurons within the injured cord appeared intact on histopathological analysis demonstrating that the alteration of excitatory amino acids occurs prior to histopathological change. Histopathological change in the white matter occurred more slowly than in the anterior and posterior horns, suggesting the spread of the lesion by secondary damage due to an autoclastic mechanism.

Post-hypoxic hypothermia reduces cerebrocortical release of NO and excitotoxins.

Hypothermia applied after hypoxia offers neuroprotection in neonatal animals, but the mechanisms involved remain unknown. Hypoxia was induced in newborn piglets and changes in excitatory amino acids (EAAs) and the citrulline:arginine ratio (CAR) were followed by microdialysis for 5 h. After the 45 min hypoxic insult, the animals were randomized to receive normothermia (39 degrees C; n=7) or hypothermia (35 degrees C; n = 7). After reoxygenation, extracellular glutamate, aspartate and the excitotoxic index were significantly lower in the cerebral cortex of hypothermic animals than in normothermic animals. A progressive rise of the CAR occurred during reoxygenation in the normothermic group whereas the ratio tended to decrease in the hypothermic group. In conclusion, post-hypoxic hypothermia attenuated NO production and overflow of EAAs.

Brain injury after hypoxia-ischemia in newborn rats: relationship to extracellular levels of excitatory amino acids and cysteine

The aim of this study was to follow extracellular concentrations of excitatory amino acids (EAAs) and cysteine during neonatal hypoxia-ischemia (HI) and reflow and to relate these events to the extent of brain damage evaluated 6 h after the insult. Rat pups (PND 7–10) were subjected to unilateral ligation of the common carotid artery and exposed to hypoxia (7.7% O 2). Extracellular amino acids were sampled during HI and for 6 h of reperfusion with microdialysis and the levels were correlated with the extent of brain damage at the site of probe placement. The concentrations of glutamate, aspartate and cysteine increased transiently during HI (15×, 6× and 3×, respectively) in the extracellular space and returned to normal or remained slightly elevated during reperfusion. Changes of EAAs and cysteine were similar during HI in the infarcted, undamaged and border-zone regions. During reperfusion the concentrations of glutamate, aspartate and cysteine were higher in infarcted and border-zone areas compared to undamaged tissue. In neonatal rats, the extracellular levels of EAAs during HI do not correspond to the extent of brain injury whereas the EAA concentrations during reflow are related to the extent of infarction.