Deferoxamine decreases the excitatory amino acid levels and improves the histological outcome in the hippocampus of neonatal rats after hypoxia-ischemia.

Hypoxic-ischemic encephalopathy is a severe complication of perinatal asphyxia and causes lifelong deficits in infants and children. Multiple mechanisms acting in serial or parallel fashion are likely to be involved in this procedure. The neuronal injury is strongly related to iron-catalysed oxygen radical production and subsequent peroxidative damage to lipids and protein. Excessive release of excitatory amino acids (EAA) glutamate and aspartate, with consequent overstimulation of glutamate receptors, is also thought to be an important mechanism in this brain injury. Deferoxamine (DFO), a chelator of non-protein-bound iron, has been shown to inhibit lipid peroxidation and hydroxyl radical production via the Fenton reaction and to decrease hypoxic-ischemic and reperfusion associated brain injury. However, the exact mechanism of neuroprotection of DFO and its possible effect on the neurotransmitters' release is currently being investigated. In the present study, a well-established model of perinatal asphyxia was used to investigate the effect of DFO on hypoxic-ischemic-induced damage to different hippocampal brain structures. DFO was administrated subcutaneously immediately after the asphyctic insult. Histological examination of the hippocampus was conducted and the tissue levels of glutamate and aspartate in the same area were determined. A remarkable reduction of hypoxia-ischemia-evoked neurons in the CA1 hippocampal region and a decrease in the asphyxia-induced hippocampal tissue levels of glutamate and aspartate was noted after DFO treatment. These findings suggest a complex action of DFO, which could be neuroprotective when administrated in the immature brain immediately after hypoxia-ischemia.     

神经节苷脂GM1对缺血缺氧后谷氨酸及其转运体神经元的作用

目的 :探讨神经节苷脂GM1对新生大鼠缺氧缺血性脑病保护作用及其可能的机理。方法 :通过建立新生鼠缺氧缺血性脑病动物模型 ,应用免疫组化方法 ,观察缺血缺氧后不同时期脑组织中谷氨酸及其转运体阳性神经元的动态变化 ,以及GM1对其的影响。结果 :缺血缺氧后 6h、1、3d大脑皮层和纹状体中谷氨酸阳性神经元明显减少 ,而谷氨酸转运体阳性神经元有所增加 ,GM1组脑组织损伤明显减轻 ,谷氨酸神经元及谷氨酸转运体神经元较单纯缺氧缺血组明显增多。结论 :神经节苷脂GM1对谷氨酸神经元具有保护作用 ,可能是通过部分提高谷氨酸转运体的表达而发挥作用     

Synergistic interaction between valproate and lamotrigine against seizures induced by 4-aminopyridine and pentylenetetrazole in mice

We compared the effects of adding a non-protective dose of valproate to increasing doses of lamotrigine with those of monotherapy and vice versa in CD1 mice. Anticonvulsant effects were evaluated against seizures induced by both 4-aminopyridine and pentylenetetrazole, and neurotoxic effects were evaluated by the rotarod test. Changes in anticonvulsants, gamma-aminobutyric acid (GABA) and glutamate concentrations in the whole brain were also assessed. Lamotrigine increased the potency ratio of valproate against 4-aminopyridine and pentylenetetrazole but not on rotarod, the protective index being increased from 1.1 to 2.4 against 4-aminopyridine and from 1.9 to 3.8 against pentylenetetrazole, without changes in brain valproate, and with a significant increase in brain GABA. Valproate increased the potency ratio of lamotrigine against 4-aminopyridine but not on rotarod, the protective index being increased from 4.4 to 7.3; valproate also increased brain lamotrigine (but only at low doses), brain GABA and brain glutamate. In conclusion, non-protective doses of lamotrigine increased the therapeutic index of valproate and vice versa, and these effects appeared to be pharmacodynamic.     

Increased anterior cingulate/medial prefrontal cortical glutamate and creatine in bipolar depression.

Proton magnetic resonance spectroscopy ((1)HMRS) is an in vivo brain imaging method that can be used to investigate psychotropic drug mechanism of action. This study evaluated baseline (1)HMRS spectra of bipolar depressed patients and whether the level of cerebral metabolites changed after an open trial of lamotrigine, an anti-glutamatergic mood stabilizer. Twenty-three bipolar depressed and 12 control subjects underwent a MRS scan of the anterior cingulate/medial prefrontal cortex. The scan was performed on a GE whole-body 1.5 T MRI scanner using single-voxel PRESS (TE/TR=30/3000 ms, 3 x 3 x 3 cm(3) and post-processed offline with LCModel. Baseline CSF-corrected absolute concentrations of glutamate+glutamine ([Glx]), glutamate ([Glu]), and creatine+phosphocreatine ([Cr]) were significantly higher in bipolar depressed subjects vs healthy controls. The non-melancholic subtype had significantly higher baseline [Glx] and [Glu] levels than the melancholic subtype. Remission with lamotrigine was associated with significantly lower post-treatment glutamine ([Gln]) in comparison to non-remission. These data suggest that non-melancholic bipolar depression is characterized by increased glutamate coupled with increased energy expenditure. Lamotrigine appears to reduce glutamine levels associated with treatment remission. Further study is encouraged to determine if these MR spectroscopic markers can delineate drug mechanism of action and subsequent treatment response.     

全脑缺血诱导沙土鼠纹状体,海马和皮层氨基酸水平的改变(英文)

目的:研究全脑缺血时沙土鼠海马、纹状体和皮层谷氨酸、天冬氨酸、γ-氨基丁酸(GABA)、谷氨酰胺、甘氨酸和牛磺酸含量的变化及氯胺酮对上述氨基酸含量的影响.方法:采用结扎双侧颈总动脉的方法制备沙土鼠全脑缺血模型,应用HPLC和荧光检测器联用测定氨基酸的含量.结果:全脑缺血显著增加沙土鼠海马,纹状体和皮层的谷氨酸,天冬氨酸,谷氨酰胺,GABA,甘氨酸和牛磺酸含量;氯胺酮(120 mg/kg,ip)预处理能完全逆转缺血诱导的谷氨酸、天冬氨酸、甘氨酸和谷氨酰胺释放的增加,但不能完全逆转缺血诱导的GABA和牛磺酸释放增加.结论:脑缺血诱发的神经元损伤可能与其增加谷氨酸、天冬氨酸、甘氨酸、谷氨酰胺含量有关,而抑制性氨基酸GABA和牛磺酸释放增加则可能是机体一种重要的自身脑保护机制.氯胺酮逆转脑缺血诱导的兴奋性氨基酸释放增加可能是其抗兴奋性神经毒的生化基础.     

Synergistic interaction between felbamate and lamotrigine against seizures induced by 4-aminopyridine and pentylenetetrazole in mice

We compared the effects of adding a nonprotective dose of felbamate to increasing single doses of lamotrigine with those of monotherapy and vice versa in CD1 mice. Anticonvulsant effects were evaluated against seizures induced by both 14 mg/kg of 4-aminopyridine and 110 mg/kg of pentylenetetrazole, and neurotoxic effects were evaluated by the rotarod test. Changes in anticonvulsants, gamma-aminobutyric acid (GABA) and glutamate concentrations in the whole brain were also assessed. Lamotrigine increased the potency ratio of felbamate against 4-aminopyridine (1.80, 95% confidence interval (CI) 1.23-2.65, P<0.05) but not against pentylenetetrazole nor on rotarod, the protective index being increased from 12.0 to 17.1 for 4-aminopyridine, with a reduction in brain felbamate, and with an increase in brain GABA. Felbamate increased the potency ratio of lamotrigine against 4-aminopyridine (4.35, 95% CI 2.05-9.25, P<0.05) but not on rotarod, the protective index being increased from 4.4 to 15.7; there were no changes in brain lamotrigine, and changes in brain GABA and/or glutamate were unrelated to the pharmacodynamic effects. In conclusion, a nonprotective dose of lamotrigine increased the therapeutic index of felbamate and vice versa, and these effects appeared to be pharmacodynamic.     

Altered time course of changes in the hippocampal concentration of excitatory and inhibitory amino acids during kainate-induced epilepsy

The temporal sequence of electrophysiological and biochemical correlates of epilepsy induced by systemic injection of kainic acid (15 mg/kg i.p.) was investigated in male rats. A significant decrease in the hippocampal concentration of glutamate and aspartate was observed 20 min after the injection. These decreases preceded both electrographic and behavioral manifestations of epilepsy, thus suggesting a causal relationship between acidic amino acid changes and the genesis of kainate-induced hyperactivity. About 30-45 min after kainate injection, a decrease in glutamate, aspartate, glycine and taurine and no change in GABA concentration were observed. Bioelectrical activity, recorded in the regio inferior (CA3) of the hippocampus or in the fascia dentata revealed the presence of high frequency bursts separated by a long-lasting depression of discharge. About 55-75 min after the injection, the number of spikes in each burst increased and the duration and frequency of interictal pauses decreased. This stage was characterized by a decrease in glutamate and aspartate, restoration to normal of glutamine, glycine and taurine and a decrease in GABA.     

Dexmedetomidine Postconditioning Reduces Brain Injury after Brain Hypoxia-Ischemia in Neonatal Rats

Perinatal asphyxia can lead to death and severe disability. Brain hypoxia-ischemia (HI) injury is the major pathophysiology contributing to death and severe disability after perinatal asphyxia. Here, seven-day old Sprague-Dawley rats were subjected to left brain HI. Dexmedetomidine was given intraperitoneally after the brain HI. Yohimbine or atipamezole, two α2 adrenergic receptor antagonists, were given 10 min before the dexmedetomidine injection. Neurological outcome was evaluated 7 or 28 days after the brain HI. Frontal cerebral cortex was harvested 6 h after the brain HI. Left brain HI reduced the left cerebral hemisphere weight assessed 7 days after the brain HI. This brain tissue loss was dose-dependently attenuated by dexmedetomidine. Dexmedetomidine applied within 1 h after the brain HI produced this effect. Dexmedetomidine attenuated the brain HI-induced brain tissue and cell loss as well as neurological and cognitive dysfunction assessed from 28 days after the brain HI. Dexmedetomidine postconditioning-induced neuroprotection was abolished by yohimbine or atipamezole. Brain HI increased tumor necrosis factor α and interleukin 1β in the brain tissues. This increase was attenuated by dexmedetomidine. Atipamezole inhibited this dexmedetomidine effect. Our results suggest that dexmedetomidine postconditioning reduces HI-induced brain injury in the neonatal rats. This effect may be mediated by α2 adrenergic receptor activation that inhibits inflammation in the ischemic brain tissues.     

血清NSE对晚期早产儿窒息脑损伤早期评价的意义

目的探讨新生儿窒息后血清神经元特异性烯醇化酶（NSE）水平变化对判断晚期早产儿脑损伤的价值。方法选取154例晚期早产儿为研究对象,其中出生时有窒息的患儿94例为实验组,于出生后3～7 d行颅脑MRI检查,依据颅脑MRI分为无脑损伤组42例和脑损伤组52例;正常的60例为对照组,所有患儿均在其出生后24 h内检测血清NSE浓度。结果窒息脑损伤组血清NSE值较窒息无脑损伤组和对照组增高,差异具有统计学意义（P〈0.05）,窒息无脑损伤组血清NSE值较对照组增高,但差异无统计学意义（P〉0.05）。结论外周血清NSE值可作为临床早期评价晚期早产儿窒息后脑损伤的参考指标。     

Cadmium chloride exposure modifies amino acid daily pattern in the mediobasal hypothalamus in adult male rat

The present study was conducted to investigate the possible effects of cadmium exposure on the daily pattern of aspartate, glutamate, glutamine, gamma‐aminobutyric acid (GABA) and taurine levels in the mediobasal hypothalamus of adult male rats. For this purpose, animals were treated with cadmium at two different exposure doses (25 and 50 mg l^?1 of cadmium chloride, CdCl₂) in the drinking water for 30 days. Control age‐matched rats received CdCl₂‐free water. After the treatment, rats were killed at six different time intervals throughout a 24 h cycle. CdCl₂ exposure modified the amino acid daily pattern, as it decreased aspartate, glutamate, GABA and taurine levels at 12:00 h with both exposure doses employed. In addition, the treatment with 25 mg l^?1 of CdCl₂ induced the appearance of minimal values at 16:00 h and maximal values between 04:00 and 08:00 h for glutamate, and a peak of glutamine content at 20:00 h. The heavy metal also decreased GABA medium levels around the clock in the mediobasal hypothalamus. However, CdCl₂ did not alter the metabolic correlation between glutamate, aspartate, glutamine and GABA observed in control animals. These results suggest that CdCl₂ induced several alterations in aspartate, glutamate, glutamine, GABA and taurine daily pattern in the mediobasal hypothalamus and those changes may be related to alterations in hypothalamic function. Copyright © 2009 John Wiley & Sons, Ltd.     

GABA turnover in the brain of rat lines developed for differential ethanol-induced motor impairment

The role of GABAergic neurons in the differential sensitivity to ethanol between the AT (Alcohol Tolerant) and ANT (Alcohol Nontolerant) rat lines developed for low and high degree of motor impairment from ethanol, was studied by comparing the effect of ethanol (2 or 4 g/kg, IP) on GABA turnover in different regions of the brain in these rat lines. GABA turnover was estimated from the accumulation of GABA after inhibition of GABA aminotransferase with aminooxyacetic acid (AOAA, 50 mg/kg, IP) given 10 min after administration of ethanol. The rats were killed two hours after the AOAA treatment with focused microwaves. The concentrations of GABA, aspartate, glutamate, glutamine and taurine were analyzed with HPLC. The saline-treated ANT rats were found to have a higher concentration of GABA in the striatum and a higher rate of GABA accumulation in the cerebellum than the AT rats. Ethanol suppressed the accumulation of GABA in both lines, but the suppression was significantly greater in the AT rats than in the ANT rats. In specific regions, this line difference was significant in the cerebral cortex and cerebellum with the higher ethanol dose. No line differences were found in the brain or tail blood ethanol concentration. AOAA increased the concentration of glutamine, decreased that of aspartate and glutamate, and did not modify that of taurine. The AOAA-induced changes in the concentrations of these amino acids were, however, minor relative to those found in the concentrations of GABA. The results that GABAergic mechanisms are involved in the differential sensitivity to the motor-impairing effects of ethanol between the AT and ANT rats.     

A method for manual determination of glutamate, glutamine, GABA and aspartate from brain regions

An improved two column method for rapid manual determination of glutamate (Glu), glutamine (Gln), gamma-aminobutyric acid (GABA) and aspartate (Asp) from brain regions is presented. The method uses a Dowex-1 column and various concentrations of acetic acid to separate Glu, Asp and the neutral amino acids. The neutral amino acids are subsequently placed on a Dowex-50 column from which potassium acetate buffers are used to separate the amido amino acids, GABA and the other neutral amino acids. The amido amino acids are hydrolysed in NaOH and the glutamine derived glutamate is separated from contaminants on another Dowex-1 column. Amino acids are manually quantitated using the fluorescence from the reaction with o-phthaldialdehyde. The method described in this paper requires no special equipment other than a fluorometer. The procedure was designed to determine levels of amino acid neurotransmitters and catecholamines from a single brain sample as small as 0.12 g, however, due to the sensitivity of the o-phthaldialdehyde reaction, levels of the four amino acids could be determined on a sample one tenth that size or smaller.     

NMDA receptor-mediated pilocarpine-induced seizures: characterization in freely moving rats by microdialysis

1. Pilocarpine administration has been used as an animal model for temporal lobe epilepsy since it produces several morphological and synaptic features in common with human complex partial seizures. Little is known about changes in extracellular neurotransmitter concentrations during the seizures provoked by pilocarpine, a non-selective muscarinic agonist.
2. Focally evoked pilocarpine-induced seizures in freely moving rats were provoked by intrahippocampal pilocarpine (10 mM for 40 min at a flow rate of 2 μl min⁻¹) administration via a microdialysis probe. Concomitant changes in extracellular hippocampal glutamate, γ-aminobutyric acid (GABA) and dopamine levels were monitored and simultaneous electrocorticography was performed. The animal model was characterized by intrahippocampal perfusion with the muscarinic receptor antagonist atropine (20 mM), the sodium channel blocker tetrodotoxin (1 μM) and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine maleate, 100 μM). The effectiveness of locally (600 μM) or systemically (10 mg kg⁻¹ day⁻¹) applied lamotrigine against the pilocarpine-induced convulsions was evaluated.
3. Pilocarpine initially decreased extracellular hippocampal glutamate and GABA levels. During the subsequent pilocarpine-induced limbic convulsions extracellular glutamate, GABA and dopamine concentrations in hippocampus were significantly increased. Atropine blocked all changes in extracellular transmitter levels during and after co-administration of pilocarpine. All pilocarpine-induced increases were completely prevented by simultaneous tetrodotoxin perfusion. Intrahippocampal administration of MK-801 and lamotrigine resulted in an elevation of hippocampal dopamine levels and protected the rats from the pilocarpine-induced seizures. Pilocarpine-induced convulsions developed in the rats which received lamotrigine perorally.
4. Pilocarpine-induced seizures are initiated via muscarinic receptors and further mediated via NMDA receptors. Sustained increases in extracellular glutamate levels after pilocarpine perfusion are related to the limbic seizures. These are arguments in favour of earlier described NMDA receptor-mediated excitotoxicity. Hippocampal dopamine release may be functionally important in epileptogenesis and may participate in the anticonvulsant effects of MK-801 and lamotrigine. The pilocarpine-stimulated hippocampal GABA, glutamate and dopamine levels reflect neuronal vesicular release.

     

Neurochemical correlates of behavior: levels of amino acids in four areas of the brain of the rat during drug-induced behavioral excitation.

The levels of GABA, aspartate, glutamate, glycine and alanine were determined in 4 specific brain areas (telencephalon, diencephalon-mesencephalon cerebellum and pons-medulla oblongata) of rats killed during a period of drug-induced behavioral excitation. Behavioral excitation was obtained in adult, male Wistar rats working on a Sidman shock-avoidance schedule following administration of 2 mg/kg tetrabenazine (TBZ) 18 hr after iproniazid (50 mg/kg) pretreatment. When compared to trained animals (working on the avoidance schedule but receiving no drugs), the excited rats had increased levels of GABA in the telencephalon and diencephalon-mesencephalon, decreased levels of aspartate in all 4 brain areas, and a lower content of glycine in the pons-medulla region. The changes in the levels of aspartate in all areas of the brain, GABA in the diencephalon-mesencephalon, and glycine in the pons-medulla were significantly correlated (p less than 0.01) with the degree of excitation. It was observed that avoidance training alone produced increases in the levels of four amino acids: aspartate in telencephalon and cerebellum, GABA in cerebellum, and glycine and glutamate in the pons-medulla. The injection of iproniazid alone or iproniazid followed by TBZ into naive animals had little effect on the levels of the five amino acids. The data are discussed in terms of aspartate and GABA interacting as neurotransmitters with cholinergic and catecholaminergic and/or serotonergic neurons to produced the behavioral excitation.     

Differential effects of vigabatrin, γ-acetylenic GABA,aminooxyacetic acid,and valproate on levels of various amino acids in rat brain regions and plasma

Drugs which elevate brain levels of the inhibitory amino acid neurotransmitter GABA by inhibiting the GABA catabolizing enzyme GABA transaminase (GABA-T) have been developed for treatment of brain disease, such as epilepsy. Among all GABA-T inhibitors available, vigabatrin is thought to be the most selective compound, and this drug is the only GABA-T inhibitor in clinical use. However, some previous studies have indicated that vigabatrin might affect the metabolism of several amino acids not directly linked to the GABA shunt. In the present study, various amino acids, involving inhibitory and excitatory neurotransmitters, were determined in 12 brain regions and plasma of rats after treatment with anticonvulsant doses of vigabatrin and the less selective GABA-T inhibitors aminooxyacetic acid (AOAA) and -acetylenic GABA (GAG). Furthermore, the antiepileptic drug valproate, which is also thought to act via the GABA system, was included for comparison. The GABA-T inhibitors markedly enhanced GABA levels in all brain regions examined, while valproate induced only moderate increases in some regions. All drugs, including valproate, significantly decreased aspartate in the brain to a similar extent, and the GABA-T inhibitors but not valproate decreased levels of glutamate. The decreases in aspartate and glutamate levels were not correlated with the different magnitudes of GABA increase produced by GABA-T inhibitors, suggesting that these effects were not simply due to the altered GABA degradation. In addition to glutamate and aspartate, alanine levels were decreased by GABA-T inhibitors but not valproate in several regions. Brain levels of glutamine were decreased by GAG and vigabatrin but increased by valproate and partly also by AOAA. Additional alterations were found in levels of glycine, taurine, serine, arginine, asparagine and threonine in some discrete brain areas. In plasma, the most marked changes in amino acids were obtained with vigabatrin, while valproate did not change plasma amino acids in rats. The data substantiate that vigabatrin is less specific than generally thought but, similar to AOAA and GAG, apparently affects several other cerebral enzymes and/or interacts with other neurotransmitter systems as well. Correspondence to: W. Löscher at the above address     

Review of lamotrigine and its clinical applications in epilepsy

Lamotrigine is an anti-epileptic agent with broad efficacy. Lamotrigine works at voltage-sensitive sodium channels, thereby stabilising the neuronal membrane and inhibiting the release of excitatory neurotransmitters such as glutamate and aspartate. Early preclinical animal studies indicate its broad-spectrum efficacy, which was later confirmed in clinical trials. Multiple randomised, placebo-controlled and comparative trials demonstrate its efficacy against partial and secondarily generalised seizures. Open-label trials show its efficacy against generalised seizures, especially absence seizures of childhood absence epilepsy and generalised seizures of juvenile myoclonic epilepsy. Lamotrigine has a wide clinical dose range and possesses favourable pharmacokinetic properties. It has a good tolerability and safety profile, which enhance compliance. Its small risk of serious skin rash should be weighed against its potential benefits when choosing lamotrigine on an individual basis. Lamotrigine is an excellent therapeutic option in epilepsy.     

Review of lamotrigine and its clinical applications in epilepsy

Lamotrigine is an anti-epileptic agent with broad efficacy. Lamotrigine works at voltage-sensitive sodium channels, thereby stabilising the neuronal membrane and inhibiting the release of excitatory neurotransmitters such as glutamate and aspartate. Early preclinical animal studies indicate its broad-spectrum efficacy, which was later confirmed in clinical trials. Multiple randomised, placebo-controlled and comparative trials demonstrate its efficacy against partial and secondarily generalised seizures. Open-label trials show its efficacy against generalised seizures, especially absence seizures of childhood absence epilepsy and generalised seizures of juvenile myoclonic epilepsy. Lamotrigine has a wide clinical dose range and possesses favourable pharmacokinetic properties. It has a good tolerability and safety profile, which enhance compliance. Its small risk of serious skin rash should be weighed against its potential benefits when choosing lamotrigine on an individual basis. Lamotrigine is an excellent therapeutic option in epilepsy.     

Effect of carbamazepine, oxcarbazepine and lamotrigine on the increase in extracellular glutamate elicited by veratridine in rat cortex and striatum

Lamotrigine, carbamazepine and oxcarbazepine inhibit veratrine-induced neurotransmitter release from rat brain slices in concentrations corresponding to those reached in plasma or brain in experimental animals or humans after anticonvulsant doses, presumably due to their sodium channel blocking properties. Microdialysis measurements of extracellular glutamate and aspartate were carried out in conscious rats in order to investigate whether corresponding effects occur in vivo. Veratridine (10 M) was applied via the perfusion medium to the cortex and the corpus striatum in the presence of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (1 mM in perfusion medium). Maximally effective anticonvulsant doses of carbamazepine (30 mg/kg), oxycarbazepine ( 60 mg/kg) and lamotrigine (15 mg/kg) were given orally.The uptake inhibitor increased extracellular glutamate and aspartate about 2-fold in striatum and about 7-fold and 3-fold, respectively, in cortex. Veratridine caused a further 2–3-fold increase in extracellular glutamate in striatum and cortex, respectively, but its effect on extracellular aspartate was less marked in both areas. None of the anticonvulsant compounds affected the veratridine-induced increases in extracellular glutamate or aspartate in the striatum which were, however, markedly inhibited by tetrodotoxin (1 M) and thus are sensitive to sodium channel blockade. In the cortex, the same drugs at the same doses did cause about 50% inhibition of the veratridine-induced increase in extracellular glutamate. Carbamazepine and to a lesser extent lamotrigine, but not oxcarbazepine, also inhibited the veratridine-induced increase in extracellular aspartate in the cortex.Although our results might seem to support the view that inhibition of glutamate and aspartate release is responsible for the anticonvulsant effects of lamotrigine, carbamazepine and oxcarbazepine, two complementary findings argue against this interpretation. First, as previously shown, inhibition of electrically induced release of glutamate requires 5 to 7 times higher concentrations of these compounds than release elicited by veratrine. Second, the present study indicates that doses totally suppressing convulsions caused no inhibition in the striatum and at best a 50% inhibition in the brain cortex. From this we conclude that the doses used here, although to some extent effective against veratridine, did not suppress the release of GLU and ASP elicited by the normal ongoing electrical activity of the glutamatergic and aspartatergic neurons and that the mechanism of the suppression of convulsions must be sought elsewhere.     

Effect of the convulsive agent 3-mercaptopropionic acid on the levels of GABA, other amino acids and glutamate decarboxylase in different regions of the rat brain

Intraperitoneal injection of 3-mercaptopropionic acid into rats caused severe convulsions which started after about 7 min. Of the amino acids examined only the level of GABA changed after 4 min and immediately before (6.5–7 min) the convulsions started. The decrease in GABA concentration detected immediately before the onset of convulsions was about 35 per cent in the cerebral cortex, corpus striatum and cerebellum, 30 per cent in pons-medulla and 20% in hippocampus. Concomitant with the fall in GABA there was a large, reversible inhibition of glutamate decarboxylase activity in the brain. The uptake of GABA into synaptosomes isolated after injection of the convulsive agent was not reduced, and the uptake of GABA into synaptosomes was not inhibited by high concentrations of 3-mercaptopropionic acid added in vitro. During convulsions levels of aspartate and taurine decreased significantly in all the brain regions investigated. A small increase in glutamine was detected in pons-medulla and in cerebellum. Major changes in the concentrations of other amino acids such as glutamate, alanine, serine and glycine were found only in corpus striatum.     

新生儿消化道出血的相关因素临床分析

目的探讨新生儿消化道出血的临床相关因素、预防和治疗。方法对57例新生儿消化道出血的临床资料进行回顾性分析。结果早产、低出生体质量及围生期窒息是患儿消化道出血发生率明显高于足月儿、正常出生体质量儿及无围生期窒息史儿(P<0.01),其他新生儿缺氧缺血性脑病、新生儿坏死性小肠结肠炎也是出血高发因素,过敏性肠病发病率呈增加趋势不容忽视。结论新生儿消化道出血是新生儿期常见急症,做好围生期保健、积极治疗原发病可明显减少新生儿消化道出血的发生率。