The Impact of Protein Glycosylation on the Identification of Patients with Pediatric Appendicitis.

The identification of pediatric appendicitis is challenging due to the lack of specific markers thereby several factors are included in the diagnostic process such as abdominal pain, ultrasonography and altered laboratory parameters (C reactive protein, absolute neutrophil cell number and white blood cell number). The glycosylation pattern of serum N-glycome was analyzed in this study of 38 controls and 40 patients with pediatric appendicitis. The glycans were released by enzymatic deglycosylation followed by fluorescent labeling and solid-phase extraction. The prepared samples were analyzed by hydrophilic interaction liquid chromatography with fluorescence and mass-spectrometric detection. The generated data were analyzed by multiple statistical tests involving the most important laboratory parameters as well. Significant differences associated with the examined patient groups were revealed suggesting the potential use of glycosylation analysis supporting the detection of pediatric appendicitis.

Comparison of Changes in the Plumage and Body Condition, Egg Production, and Mortality of Different Non-Beak-Trimmed Pure Line Laying Hens during the Egg-Laying Period.

The experiment was carried out with altogether 1740 non-beak-trimmed laying hens, which originated from Bábolna TETRA Ltd., representing two different types (Rhode Island Red (RIR) and Rhode Island White (RIW)) and four different lines (Lines 1-2: RIR, Lines 3-4: RIW). The plumage and body condition of randomly selected 120 hens (30 hens/line) was examined at 20, 46, and 62 weeks of age. The egg production and the mortality of the sampled hens were recorded daily. Based on the results, it was established that the lines differ clearly in most of the examined traits. It was also pointed out that injurious pecking of the hens resulted not only in damages in the plumage but also in the body condition. The results obviously demonstrated that the highest egg production and the lowest mortality rate were reached by those hens, which had the best plumage and body condition. Because the occurrence of injurious pecking seems to depend on the genetic background, selection of the hens (lines, families, individuals) for calm temperament will be very important in the future in order to maintain the high production level in non-beak-trimmed layer flocks.

A Dilute and Shoot Strategy for Determining Alternaria Toxins in Tomato-Based Samples and in Different Flours Using LC-IDMS Separation.

Alternaria toxins are emerging mycotoxins whose regulation and standardization are in progress by the European Commission and the European Committee for Standardization. This paper describes a dilute and shoot approach to determine five Alternaria toxins in selected food samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The strategy involves sample extraction with acidified aqueous methanol, followed by a solvent change accomplished via sample evaporation and reconstitution. The quantification is based on isotope dilution, applying all corresponding isotopically labeled internal standards to compensate possible matrix effects of the analysis. The main advantages of the present method over other existing methods includes simple and effective sample preparation, as well as detection with high sensitivity. The five-fold sample dilution can decrease matrix effects, which were evaluated with both external and internal standard methods. The results demonstrated a limit of quantification lower than 1.0 µg/kg for all five analytes for the first time. The newly presented method showed acceptable accuracy (52.7-111%) when analyzing naturally contaminated and spiked standard samples at the described levels. The method was validated for tomato-based and flour samples (wheat, rye, and maize). The absolute recovery ranged from 66.7% to 91.6% (RSD < 10%). The developed method could be an alternative approach for those laboratories that exclude sample cleanup and pre-concentration of state-of-the-art instruments with enhanced sensitivity.

Stress Resilience is Associated with Hippocampal Synaptoprotection in the Female Rat Learned Helplessness Paradigm.

The synaptogenic hypothesis of major depressive disorder implies that preventing the onset of depressive-like behavior also prevents the loss of hippocampal spine synapses. By applying the psychoactive drugs, diazepam and fluoxetine, we investigated whether blocking the development of helpless behavior by promoting stress resilience in the rat learned helplessness paradigm is associated with a synaptoprotective action in the hippocampus. Adult ovariectomized and intact female Sprague-Dawley rats (n = 297) were treated with either diazepam, fluoxetine, or vehicle, exposed to inescapable footshocks or sham stress, and tested in an active escape task to assess helpless behavior. Escape-evoked corticosterone secretion, as well as remodeling of hippocampal spine synapses at a timepoint representing the onset of escape testing were also analyzed. In ovariectomized females, treatment with diazepam prior to stress exposure prevented helpless behavior, blocked the loss of hippocampal spine synapses, and muted the corticosterone surge evoked by escape testing. Although fluoxetine stimulated escape performance and hippocampal synaptogenesis under non-stressed conditions, almost all responses to fluoxetine were abolished following exposure to inescapable stress. Only a much higher dose of fluoxetine was capable of partly reproducing the strong protective actions of diazepam. Importantly, these protective actions were retained in the presence of ovarian hormones. Our findings indicate that stress resilience is associated with the preservation of spine synapses in the hippocampus, raising the possibility that, besides synaptogenesis, hippocampal synaptoprotection is also implicated in antidepressant therapy.

Structural Evaluation and Electrophysiological Effects of Some Kynurenic Acid Analogs.

Kynurenic acid (KYNA), a metabolite of tryptophan, as an excitatory amino acid receptor antagonist is an effective neuroprotective agent in case of excitotoxicity, which is the hallmark of brain ischemia and several neurodegenerative processes. Therefore, kynurenine pathway, KYNA itself, and its derivatives came into the focus of research. During the past fifteen years, our research group has developed several neuroactive KYNA derivatives, some of which proved to be neuroprotective in preclinical studies. In this study, the synthesis of these KYNA derivatives and their evaluation with divergent molecular characteristics are presented together with their most typical effects on the monosynaptic transmission in CA1 region of the hippocampus of the rat. Their effects on the basic neuronal activity (on the field excitatory postsynaptic potentials: fEPSP) were studied in in vitro hippocampal slices in 1 and 200 µM concentrations. KYNA and its derivative 4 in both 1 and 200 µM concentrations proved to be inhibitory, while derivative 8 only in 200 µM decreased the amplitudes of fEPSPs. Derivative 5 facilitated the fEPSPs in 200 µM concentration. This is the first comparative study which evaluates the structural and functional differences of formerly and newly developed KYNA analogs. Considerations on possible relations between molecular structures and their physiological effects are presented.

The Glutamine Transporter Slc38a1 Regulates GABAergic Neurotransmission and Synaptic Plasticity.

GABA signaling sustains fundamental brain functions, from nervous system development to the synchronization of population activity and synaptic plasticity. Despite these pivotal features, molecular determinants underscoring the rapid and cell-autonomous replenishment of the vesicular neurotransmitter GABA and its impact on synaptic plasticity remain elusive. Here, we show that genetic disruption of the glutamine transporter Slc38a1 in mice hampers GABA synthesis, modifies synaptic vesicle morphology in GABAergic presynapses and impairs critical period plasticity. We demonstrate that Slc38a1-mediated glutamine transport regulates vesicular GABA content, induces high-frequency membrane oscillations and shapes cortical processing and plasticity. Taken together, this work shows that Slc38a1 is not merely a transporter accumulating glutamine for metabolic purposes, but a key component regulating several neuronal functions.

Novel therapeutic potential of angiotensin receptor 1 blockade in a rat model of diabetes-associated depression parallels altered BDNF signalling.

AIMS/HYPOTHESIS: Diabetes is a worldwide epidemic linked with diverse diseases of the nervous system, including depression. A few studies suggested a connection between renin-angiotensin-aldosterone system blockers and reduced depressive symptoms, although underlying mechanisms are unclear. Here we investigated the antidepressant effect and the mechanisms of action of the angiotensin receptor 1 blocker (ARB) losartan in an experiential model of diabetes-associated depression. METHODS: Experimental diabetes was induced by streptozotocin in adult male Wistar rats. After 5 weeks of diabetes, rats were treated for 2 weeks with a non-pressor oral dose of losartan (20 mg/kg). In protocol 1, cerebrovascular perfusion and glial activation were evaluated by single-photon emission computed tomography-MRI and immunohistochemistry. In protocol 2, behaviour studies were performed (forced swim test and open field test). Hippocampal proinflammatory response and brain-derived neurotrophic factor (BDNF) signalling were also assessed. RESULTS: Here, we show that diabetic rats exhibit depression-like behaviour, which can be therapeutically reversed by losartan. This action of losartan occurs via changes in diabetes-induced neuroinflammatory responses rather than altered cerebral perfusion. We also show that as a part of its protective effect losartan restores BDNF production in astrocytes and facilitates BDNF-tropomyosin receptor kinase B-cAMP response element-binding protein signalling in the diabetic brain. CONCLUSIONS/INTERPRETATION: We identified a novel effect of losartan in the nervous system that may be implemented to alleviate symptoms of diabetes-associated depression. These findings explore a new therapeutic horizon for ARBs as possible antidepressants and suggest that BDNF could be a target of future drug development in diabetes-induced complications.

Absolute Lymphocyte Count (ALC) after Induction Treatment Predicts Survival of Pediatric Patients with Acute Lymphoblastic Leukemia.

Absolute Lymphocyte Count (ALC) has been recently established as a prognostic factor of survival in pediatric Acute Lymphoblastic Leukemia (ALL). A retrospective analysis of 132 patients treated according the BFM - ALLIC 2002 protocol was performed in a single institution. A possible association between ALC values and Overall Survival (OS) or Event-Free Survival (EFS) was evaluated at multiple time points during induction chemotherapy. ALC higher than 350 cells/µL measured on the 33th day of induction was associated with better Overall- and Event-Free Survival in both Kaplan-Meier (OS 88.6% vs. 40%; p < 0.001 / EFS 81.6% vs. 30%; p < 0.001) and Cox regression (OS HR 8.77 (3.31-23.28); p < 0.001) and EFS HR 6.61 (2.79-15.63); p < 0.001) analyses. There was no association between survival and measured ALC values from earlier time points (day of diagnosis, days 8 and 15) of induction therapy. Patients with low ALC values tend to have higher risk (MR or HR groups) and a higher age at diagnosis (>10 years). With help of day 33 ALC values of 350 cells/µL cutoff it was possible to refine day 33 flow cytometry (FC) Minimal Residual Disease (MRD) results within the negative cohort: higher ALC values were significantly associated with better survival. ALC on day 33 (350 cells/µL) remained prognostic for OS and EFS in multivariate analysis after adjusting it for age, cytogenetics, immunophenotype and FC MRD of induction day 33. According to these findings ALC on day 33 of induction is a strong predictor of survival in pediatric ALL.

Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen-glucose deprivation.

Hypoxic circumstances result in functional and structural impairments of the brain. Oxygen-glucose deprivation (OGD) on hippocampal slices is a technique widely used to investigate the consequences of ischemic stroke and the potential neuroprotective effects of different drugs. Acetyl-l-carnitine (ALC) is a naturally occurring substance in the body, and it can therefore be administered safely even in relatively high doses. In previous experiments, ALC pretreatment proved to be effective against global hypoperfusion. In the present study, we investigated whether ALC can be protective in an OGD model. We are not aware of any earlier study in which the long-term potentiation (LTP) function on hippocampal slices was measured after OGD. Therefore, we set out to determine whether an effective ALC concentration has an effect on synaptic plasticity after OGD in the hippocampal CA1 subfield of rats. A further aim was to investigate the mechanism underlying the protective effect of this compound. The experiments revealed that ALC is neuroprotective against OGD in a dose-dependent manner, which is manifested not only in the regeneration of the impaired synaptic transmission after the OGD, but also in the inducibility and stability of the LTP. In the case of the most effective concentration of ALC (500µM), use of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) revealed that the PI3K/Akt signaling pathway has a key role in the restoration of the synaptic transmission and plasticity reached by ALC treatment.

A simple novel technique to induce short-lasting local brain ischaemia in the rat.

AIMS: Brain ischaemia models are essential to study the pathomechanisms of stroke. Our aim was to investigate the reliability and reproducibility of our novel focal ischaemia-reperfusion model. METHODS: To induce a cortical transient ischaemic attack, we lifted the distal middle cerebral artery (MCA) with a special hook. The early changes after 2 × 15-min occlusion were observed in the somatosensory evoked responses (SERs). The histological responses to 2 × 15-min MCA occlusion and to 30-, 45- or 60-min ischaemia were examined after a 1-day survival period by 2,3,5-triphenyltetrazolium chloride (TTC) and Fluoro Jade C (FJC) staining. Another group, with 30-min ischaemia, was analysed histologically by FJC, S100 and CD11b labelling after a 5-day survival period. RESULTS: The amplitudes of the SERs decreased immediately at the beginning of the ischaemic period, and remained at a reduced level during the ischaemia. Reperfusion resulted in increasing SER amplitudes, but they never regained the control level. The short-lasting ischaemia did not lead to brain infarction when evaluated with TTC, but intense labelling was found with FJC. The 30-min ischaemia did not result in FJC labelling after 1 day, but marked labelling was observed after 5 days with FJC, S100 and CD11b in the cortical area supplied by the MCA. CONCLUSIONS: We present here a novel, readily reproducible method to induce focal brain ischaemia. The ischaemia-reperfusion results in noteworthy changes in the SERs and the appearance of conventional tissue damage markers. This method involves possibilities for precise blood flow regulation, and the setting of the required level of perfusion.

Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood-brain barrier permeability.

Cortical spreading depression (CSD) involves a slowly-propagating depolarization wave in the cortex, which can appear in numerous pathophysiological conditions, such as migraine with aura, stroke, and traumatic brain injury. Neurons and glial cells are also depolarized transiently during the phenomena. CSD is followed by a massive increase in glutamate release and by changes in the brain microcirculation. The aim of this study was to investigate the effects of two N-methyl-D-aspartate receptor antagonists, endogenous kynurenic acid (KYNA) and dizocilpine, on CSD and the related blood-brain barrier (BBB) permeability in rats. In intact animals, KYNA hardly crosses the BBB but has some positive features as compared with its precursor L-Kynurenine, which is frequently used in animal studies (KYNA cannot be metabolized to excitotoxic agents such as 3-hydroxy-L-kynurenine and quinolinic acid). We therefore investigated the possible effects of peripherally administered KYNA. Repetitive CSD waves were elicited by the application of 1 M KCl solution to the cortex. Direct current-electrocorticograms were measured for 1 hour. Four parameters of the waves were compared. Evans blue dye and fluorescent microscopy were used to study the possible changes in the permeability of the BBB. The results demonstrated that N-methyl-D-aspartate receptor antagonists can reduce the number of CSD waves and decrease the permeability of the BBB during CSD. These results suggest that KYNA itself or its derivatives may offer a new approach in the therapy of migraines.

Effects of vasoactive substances on the neurovascular structures and microcirculation in the developing callus 10 and 15 days after bone injury.

The developing callus requires sufficient oxygen and substrate supply. Despite the importance of these processes, we have limited understanding of regulation of the callus microcirculation. We aimed to assess the role of vasoactive substances in the microcirculation of the callus in a gap osteotomy model in the rabbit detected by laser-Doppler flowmetry. The reactions were elicited with locally applied vasoactive substances: epinephrine (E), calcitonine-gene related protein (CGRP), substance P (SP), sodium nitroprusside (SNP) and Ebrantil (Ebr) on the 10th and 15th postoperative days. Changes of the circulatory parameters were compared to changes in the ipsilateral femoral bone marrow. Perfusion pressure, maximal change of the blood flow and 50% recovery time (50RT) of the flow reactions and peripheral micro vascular resistance (MVR) was calculated. Systemic blood pressure (BP) was measured directly with an arterial catheter. Reactive neurovascular structures, sensitive to neuropeptides and vasoactive substances, appear at a very early stage of callus formation. On the 10th postoperative day, 2/3 of the blood flow velocity of the intact tibia has already returned, and the values are higher on the 15th postoperative day than those of the intact tibia. The basal blood flow velocities (prior to administration of any substance) are significantly higher on the 15th postoperative day than on the 10th.

Behavioural studies with a newly developed neuroprotective KYNA-amide.

The neuroactive properties and neuroprotective potential of endogenous L: -kynurenine, kynurenic acid (KYNA) and its derivatives are well established. KYNA acts as an antagonist on the obligatory co-agonist glycine site, and has long been at the focus of neuroprotective trials. Unfortunately, KYNA is barely able to cross the blood-brain barrier. Accordingly, the development and synthesis of KYNA analogs which can readily cross the BBB have been at the focus of research interest with the aim of neuroprotection. Earlier we reported a new KYNA-amide crosses the BBB and proved neuroprotective in several experiments. In the present study, we investigated the locomotor activity, working memory performance, and also the long-lasting, consolidated reference memory of animals treated intraperitoneally (i.p.) with the novel analog. The effects of the novel analog on the spatial orientation and learning ability of rats were assessed in the Morris water maze (MWM) paradigm. The effects on locomotor activity of mice was assessed in the open field (OF) paradigm, and those on the spatial orientation and learning ability of mice were investigated in the radial arm maze (RAM) paradigm. It emerged that there is a dose of this KYNA-amide which is neuroprotective, but does not worsen the cognitive function of the brain. This result is significant in that a putative neuroprotectant without adverse cognitive side-effects is of great benefit.

Kainate postconditioning restores LTP in ischemic hippocampal CA1: onset-dependent second pathophysiological stress.

Postconditioning can be induced by a broad range of stimuli within minutes to days after an ischemic cerebral insult. A special form is elicited by pharmacological intervention called second pathophysiological stress. The present study aimed to evaluate the effects of low-dose (5 mg/kg) kainate postconditioning with onsets 0, 24 and 48 h after the ischemic insult on the hippocampal synaptic plasticity in a 2-vessel occlusion model in rat. The hippocampal function was tested by LTP measurements of Schaffer collateral-CA1 pyramidal cell synapses in acute slices and the changes in density of Golgi-Cox-stained apical dendritic spines. Postconditioning 0 and 24 h after ischemia was not protective, whereas 48-h-onset postconditioning resulted in the reappearance of a normal spine density (>100,000 spines) 3 days after ischemia, in parallel with the long-term restoration of the damaged LTP function. Similar, but somewhat less effects were observed after 10 days. Our data clearly demonstrate the onset dependence of postconditioning elicited by a subconvulsant dose of kainate treatment in global ischemia, with restoration of the structural plasticity and hippocampal function.

Neuroprotection with a new kynurenic acid analog in the four-vessel occlusion model of ischemia.

Global forebrain ischemia results in damage to the pyramids in the CA1 hippocampal subfield, which is particularly vulnerable to excitotoxic processes. Morphological and functional disintegration of this area leads to a cognitive dysfunction and neuropsychiatric disorders. Treatment with N-methyl-d-aspartate receptor antagonists is a widely accepted method with which to stop the advance of excitotoxic processes and concomitant neuronal death. From a clinical aspect, competitive glycine- and polyamine-site antagonists with relatively low affinity and moderate side-effects are taken into account. Endogenous kynurenic acid acts as an antagonist on the obligatory co-agonist glycine site, and has long been at the focus of neuroprotective trials. In the present study, we estimated the neuroprotective capability of a novel kynurenic acid analog in transient global forebrain ischemia, measuring the rate of hippocampal CA1 pyramidal cell loss and the preservation of long-term potentiation at Schaffer collateral-CA1 synapses. The neuroprotective potential was reflected by a significantly diminished hippocampal CA1 cell loss and preserved long-term potentiation expression. The neuroprotective effect was robust in the event of pretreatment, and also when the drug was administered at the time of reperfusion. This result is beneficial since a putative neuroprotectant proven to be effective as post-treatment is of much greater benefit.

Effects of blood glutamate scavenging on cortical evoked potentials.

It is well known that traumatic or ischemic brain injury is followed by acute excitotoxicity caused by the presence of abnormally high glutamate (Glu) in brain fluids. It has recently been demonstrated that excess Glu can be eliminated from brain into blood following the intravenous administration of oxaloacetate (OxAc), which, by scavenging blood Glu, induces an enhanced and neuroprotective brain-to-blood Glu efflux. In this study, we subjected rats to intravenous OxAc administration (i.v., 12.5, 25, and 50 mg/kg, respectively), and studied its effects on somatosensory evoked cortical potentials (EPs). Against our expectation, the amplitudes of EPs did not decrease but increased in a dose- and time-dependent manner after OxAc administration. Similar effects were observed when blood Glu scavenging was enhanced by combining OxAc (12.5 mg/kgbw) with recombinant glutamate-oxaloacetate transaminase (GOT, 0.14 nmol/100 g rat). On the basis of these results, we suggest that the changes of amplitudes of the EPs involve not only a glutamatergic but also the weakening of a GABAergic component. We cannot rule out the possibility that OxAc penetrates into the brain and improves mitochondrial functions.

Calcitonin gene-related peptide, substance P, nitric oxide and epinephrine modulate bone marrow micro circulation of the rabbit tibia and femur.

Different bones have different blood supplies, which may influence bone healing. Therefore, elucidation of the mechanisms involved in the regulation of bone marrow blood flow in different bones is of high clinical importance. To assess the micro circulation of bone marrow of the femur and tibia simultaneously, flow velocities were continuously measured by a two-channel laser-Doppler flowmeter. The probes were introduced into the femoral and tibial diaphysis, respectively, in the anesthetized rabbit. Changes in micro circulation of the bone marrow were elicited by intra-arterial bolus injections of vasoactive substances: epinephrine (E), calcitonine-gene related peptide (CGRP), substance P (SP), sodium nitroprusside (SNP), E and Ebrantil. Systemic arterial blood pressure was recorded with an electro-manometer. Micro vascular resistance (MVR) and 50% recovery time (50RT) to baseline flow level were calculated from the measured data. Flow velocity in the femur was significantly higher. Epinephrine considerably reduced micro vascular blood flow, which could be significantly warded off by Ebrantil. CGRP and SP did not change MVR. Application of SNP resulted in reduction of flow velocity, but it also decreased MVR. No statistically significant differences were found between reactions of the micro circulation in the two marrows. These results suggest that there are no significant differences between the blood flow response patterns of these two bone marrow sites, thus the regulation patterns of the micro circulation of the two bones are also similar.

A novel kynurenic acid analogue: a comparison with kynurenic acid. An in vitro electrophysiological study.

Kynurenic acid is an endogenous product of the tryptophan metabolism, and as a broad-spectrum antagonist of excitatory amino acid receptors may serve as a protective agent in neurological disorders. The use of kynurenic acid as a neuroprotective agent is rather limited, however, because it has only restricted ability to cross the blood-brain barrier. Accordingly, new kynurenic acid analogues which can readily cross the blood-brain barrier and exert their complex anti-excitotoxic activity are greatly needed. Such a novel analogue, 2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one hydrochloride, has been developed and tested. In an in vitro electrophysiological study, in which its properties were compared with those of kynurenic acid, the new analogue behaved quite similarly to kynurenic acid: in the micromolar range, its administration led to a decrease in the amplitudes of the field excitatory postsynaptic potentials in the CA1 region of the hippocampus, while in nanomolar concentrations it did not give rise to inhibition, but, in fact, facilitated the field excitatory postsynaptic potentials. Moreover, the new analogue demonstrated similar protective action against PTZ-induced facilitation to that observed after kynurenic acid administration. The findings strongly suggest that the neuroactive effects of the new analogue are comparable with those of kynurenic acid, but, in contrast with kynurenic acid, it readily crosses the blood-brain barrier. The new analogue may therefore be considered a promising candidate for clinical studies.

Effects of neuropeptides and vasoactive substances on microcirculation of the callus after tibial osteotomy in rabbits.

Previous studies have demonstrated a dynamic ingrowth of vessels into the developing callus. In this study, maturation and development of the regulation of microcirculation were followed in the callus of rabbits. In the first series, the effects of vasoactive substances on blood flow velocity, perfusion pressure, duration of effects and peripheral vascular resistance of the bone marrow in the femur and tibia were compared. In the second series, the same parameters were measured in the femur and in the developing callus 10 and 15 days following gap osteotomy of the tibia. There were no significant differences between the microcirculatory reactions of the intact femur and tibia. Basal blood flow could be verified in the callus on the 10th postoperative day. No vascular reactions could be elicited. Basal blood flow velocity was higher on the 15th day, when compared to the measurements on the 10th day. The substances elicited statistically significant differences in flow velocity, resistance and 50% recovery time in the callus on the 15th day. Blood flow reactions of the ipsilateral femoral and tibial bone marrow are identical, thus the femur can serve as a reference site for blood flow measurements in the callus. Regulation and maturation of callus microcirculation develop rapidly between the 10th and 15th days.

Oxaloacetate decreases the infarct size and attenuates the reduction in evoked responses after photothrombotic focal ischemia in the rat cortex.

A traumatic brain injury or a focal brain lesion is followed by acute excitotoxicity caused by the presence of abnormally high glutamate (Glu) levels in the cerebrospinal and interstitial fluids. It has recently been demonstrated that this excess Glu in the brain can be eliminated into the blood following the intravenous administration of oxaloacetate (OxAc), which, by scavenging the blood Glu, induces an enhanced and neuroprotective brain-to-blood Glu efflux. In this study, we subjected rats to a photothrombotic lesion and treated them after the illumination with a single 30-min-long administration of OxAc (1.2 mg/100 g, i.v.). Following induction of the lesion, we measured the infarct size and the amplitudes of the somatosensory evoked potentials (SEPs) as recorded from the skull surface. The photothrombotic lesion resulted in appreciably decreased amplitudes of the evoked potentials, but OxAc administration significantly attenuated this reduction, and also the infarct size assessed histologically. We suggest that the neuroprotective effects of OxAc are due to its blood Glu-scavenging activity, which, by increasing the brain-to-blood Glu efflux, reduces the excess Glu responsible for the anatomical and functional correlates of the ischemia, as evaluated by electrophysiological evoked potential (EP) measurements.