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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excitatory dicarboxylic amino acid neurotransmitters, particularly glutamate, have been implicated in mediating neuronal cell injury in brain ischemia-anoxia, epilepsy, and stroke. Glutamate neurotoxicity has been demonstrated in several in vitro models, as well as its prevention by a variety of agents, including several sialic acid-containing glycosphingolipid species, gangliosides. We have now examined ganglioside effects in anoxic exposed cultures of granule cells from Postnatal Day 8 rat cerebellum. Cells between 10 and 12 days in vitro were placed into an anoxic atmosphere or subjected to a chemical model of anoxia by a pulse exposure to rotenone. Widespread neuronal degeneration of neuronal cell bodies and their associated neurite network was seen the following day. These effects on cell vitality at the morphological level were quantitatively confirmed by measuring the photometric reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide to a blue formazan product. This neuronal injury was abolished by the specific N-methyl-D-aspartate receptor noncompetitive antagonists Mg2+, phencyclidine and MK-801, suggesting that this subtype of glutamate receptor is involved in the pathogenesis of anoxic granule cell injury. Pretreatment for 30 to 60 min or more or concurrent treatment with ganglioside GM1 largely prevented the ensuing neuronal death (ED50 = 25 microM), even 4 days later. Degeneration induced by exogenous glutamate was equally reduced. Asialo GM1 (lacking sialic acid) was ineffective. These results are consistent with the observed beneficial effects of the gangliosides in ischemic brain injury models in vivo.
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PMID:Monosialoganglioside GM1 protects against anoxia-induced neuronal death in vitro. 268 18

A miniature multiple thin-film recording sensor was used to measure simultaneously the electrical activity, oxygen content and temperature of brain tissue. The chamber-type potential sensor was an Ag/AgCl electrode covered by an Si3N4 (silicon nitride) chamber. The chamber-type oxygen sensor consisted of an Au-Ag/AgCl two-electrode electrochemical cell embedded in an electrolyte-filled Si3N4 chamber. The temperature sensor was a thin-film germanium resistor. The different sensors were spaced 300 microns apart. Anaesthetics (pentobarbital, chloral hydrate, chlornembutal, halothane) were shown to depress electrical activity and to increase local oxygen tension in the hippocampus. Halothane, but not the other anaesthetics, also increased the current output of the oxygen sensor when tested in saline bath, indicating that the apparent increase in measured oxygen levels during halothane anaesthesia was partly due to an electrochemical effect of halothane on the oxygen sensors. The decrease of tissue oxygen consumption produced by the other anaesthetics is likely to be the result of metabolic depression. Cerebral ischemia, evoked by cauterization of the vertebral arteries and occlusion of the carotid arteries for 30 min, resulted in the disappearance of both spontaneous and evoked electrical activity in the hippocampus and a decrease of both local temperature and oxygen tension. There was a marked overshoot of the oxygen tension to above preocclusion level following the release of the carotid arteries. As soon as electrical activity returned, the oxygen tension fell again, often below the lowest level seen during the ischemic period. This secondary decrease of oxygen level could be reversed by administration of supplementary small doses of anaesthetic. The anaesthetic-induced increase in oxygen tension was accompanied by a marked decrease in electroencephalogram amplitude and frequency. During electrically induced seizures a decrease in hippocampal oxygen content occurred and was accompanied by an increase of local temperature. Since the rectal temperature was kept constant, the changes in temperature are likely to reflect changes in blood perfusion of the recorded area. These findings are in agreement with previous observations made with conventional electrodes. In addition, the miniature size of the chamber-type microelectrode assembly allows a correlated monitoring of parallel physiological changes with high spatial and temporal resolution during anaesthesia, ischemia and epilepsy.
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PMID:Simultaneous recording of local electrical activity, partial oxygen tension and temperature in the rat hippocampus with a chamber-type microelectrode. Effects of anaesthesia, ischemia and epilepsy. 271 Mar 29

Glucose metabolism is altered in various pathologic conditions in the brain, i. e. ischemia, epilepsy and hypoglycemia. Therefore, analysis of glucose metabolism in pathologic conditions needs careful investigation of that in steady state. 13C-NMR method allows continuous sequential monitoring of changes in metabolism of glucose in vivo. The natural abundance of 13C is quite low (1.1%) and by administering 13C labelled in various skeleton in glucose, it is possible to monitor the metabolites in vivo. In this study, 13C glucose labelled in 1-position of carbon was employed to investigate the metabolic pathways in the control and transient ischemic gerbil brain with reperfusion. Male mongolian gerbils weighing 60-80 g were employed in this study. The gerbils were anesthetized by intraperitoneal administration of pentobarbital. The right skull was exposed and a surface coli was placed directly above the skull bone. After the operation, the animals were fastened to the NMR probe vertically. 500 mg/kg of [1-13C] glucose was injected via femoral catheter. 13C-NMR spectra were serially obtained before and after injection with GX-270 NMR spectrometer (JEOL, Tokyo, Japan, 6.34 T). In other series of experiments, 30 minutes of cerebral ischemia were induced after 15 minutes of glucose injection by the bilateral common carotid artery occlusion. In the normal gerbil brain, after administration of [1-13C] glucose (500 mg/kg), alpha and beta-anomers of [1-13C] glucose peak appeared abruptly and reached its peak level at 7.5-15 min acquisition period. The C2 peak representing glutamate and/or glutamine appeared later. The C3 and C4 peak started to appear even later at 30-40 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The metabolism of glucose monitored by 13C-NMR in the gerbil brain in vivo-natural course and application to the ischemic model]. 273 47

In this chapter, the pathophysiology and neurochemical pathology of epileptic brain damage is discussed on the basis of an integrative approach in which a comparison is made to cell necrosis resulting from ischemia and hypoglycemia. Two main questions are asked. First, is the brain damage resulting from these three disorders of cerebral energy metabolism similar in distribution and structural characteristics, as previously proposed? Second, is it possible to identify one or several neurochemical events, at the cellular and subcellular level, that qualify as the final common pathways leading to neuronal necrosis? A related question is, will seizures cause structural damage even if they do not critically curtail cellular oxygen supply? A review of the literature and of recent results obtained in animals with long-term recovery following status epilepticus of known duration suggests that although brain damage caused by epilepsy shows some similarities to that incurred due to ischemic and hypoglycemic insults, it is far from identical. In well oxygenated animals with an adequate cardiovascular function, 2 hr of status epilepticus causes moderate neuronal necrosis in the cerebral cortex (layers 3-4), the hippocampus (CA4 and CA1 pyramidal cells), and the thalamus (ventromedial nuclei). In rats, status epilepticus of 30 min duration or longer invariably causes infarction of the substantia nigra (pars reticularis), with some affectation of globus pallidus as well. Notably, CA3 pyramids and dentate neurons are spared, as is the pars compacta of the substantia nigra. Neurochemical events in ischemia, hypoglycemia, and status epilepticus show some striking dissimilarities, yet all three conditions lead to neuronal necrosis. In complete or near-complete ischemia, in which metabolic rate virtually ceases; deterioration of tissue energy state is rapid and extensive, with dramatic loss of ion homeostasis; cellular redox systems are reduced; and acidosis is marked to excessive. In hypoglycemic coma, oxygen consumption continues, albeit at a reduced rate; loss of high energy phosphates is extensive but less than complete, as is loss of ion homeostasis; cellular redox system become oxidized; and acidosis is absent. In epileptic seizures, finally, metabolic rate is markedly enhanced; perturbation of tissue energy state and of ion homeostasis is minimal to small; and acidosis is moderate. Results obtained in experimental animals suggest that neuronal necrosis, when incurred, is unrelated to energy failure and occurs in spite of adequate cellular oxygenation. Four neurochemical events are common to all three conditions discussed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epileptic brain damage: pathophysiology and neurochemical pathology. 287 25

Ischemia, hypoglycemia, and epilepsy have long been thought to produce similar or identical brain damage. Furthermore, these insults have been assumed to be additive in their damaging effects. These notions have been based on neuropathological observations in the hippocampus and cerebral cortex, and on the tenet that energy failure (ischemia, hypoglycemia) and increased demand for energy (epilepsy) similarly give rise to selective neuronal necrosis. Recently, other bases for considering these three insults identical have grown out of observations that loss of calcium homeostasis is common to all and that an excitotoxic mechanism of selective neuronal necrosis exists in all three conditions. Fundamental differences between ischemia, hypoglycemia, and epilepsy include the underlying neurochemical changes induced, the neuronal revival times, the time course of neuronal death, the distribution of selective neuronal necrosis, and the likely excitotoxins released. Lactic acid accumulation, implicated in damage to the neuropil as well as to neuronal cell bodies, also occurs to different degrees and in different distributions in the three conditions. The degree and distribution of pannecrosis is thus also different in ischemia, hypoglycemia, and epilepsy.
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PMID:Biological differences between ischemia, hypoglycemia, and epilepsy. 306 62

The most important premise for a successful surgical treatment of epilepsy lies in an accurate diagnosis of the focus location. The hitherto employed methods for this purpose are meticulous analysis of seizure contents and scalp EEGs, but spatial localization of the focus sites is far beyond the capacity of these diagnostic measures. With the advent of positron emission tomography (PET), in vivo observation of human brain metabolism has become possible. The indices of brain metabolism such as cerebral blood flow (rCBF), cerebral metabolic rate of glucose or oxygen (CMRG, CMRO2) are noninvasively measured by PET offering priceless information for diagnosing brain dysfunction such as ischemia, degeneration, psychosis, or epilepsy. Kuhl et al. first employed PET in assessment of epileptic foci, in which interictal foci were beautifully detected as discrete "hypometabolic zones". Many researchers have confirmed this invaluable finding, and nowadays PET seems to have acquired the citizenship as one of the most capable diagnostic measures in focus localization. We have hitherto applied PET study in 72 epileptic patients. The main contents of their seizures consists of complex partial in 32, elementary partial in 32, generalized in 6, and others in 3 cases. We administered perorally 10 mCi glucose labeled with C11 produced in the JSW Baby Cyclotron for the study of CMRG. The continuous inhalation method of CO2 and O2 labeled with O15 produced in the same cyclotron was also employed for measurement of rCBF and CMRO2. In both studies, epileptic foci were shown as well demarcated hypometabolic zones with decreased CMRG, rCBF or CMRO2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Surgical treatment of convexity focal epilepsy--based on diagnosis of PET and subdural EEG]. 310 88

Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.
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PMID:Etiologic and preventive aspects of epilepsy in the child--bridging the gap between laboratory and clinic. 330 92

N-methyl-D,L-aspartate (NMA) antagonists are of potential value in the treatment of epilepsy and ischemia, but commonly utilized compounds are of low potency and poorly penetrate the brain. Tiletamine hydrochloride is a lipophilic and potent veterinary anesthetic. This study shows tiletamine to be similar to ketamine and to phencyclidine, agents known to interact with the NMA receptor. Effects of tiletamine on synaptic transmission and on direct excitatory responses to exogenous amino acids were examined in rat hippocampal and striatal slices. In striatal slices, tiletamine inhibited the NMA-mediated, but not the spontaneous, release of [3H]acetylcholine, with an IC50 of 70 nM. In hippocampal CA1 cells, 3 microM tiletamine in the perfusate reversibly blocked the intracellularly recorded responses to ionophoretically applied NMA, but not to glutamate, quisqualate and kainate. Tiletamine, 3 to 100 microM, had no effect on the orthodromically elicited excitatory postsynaptic potential, action potential amplitude or duration, resting membrane potential, or input resistance. In Mg++-free perfusate, the excitatory postsynaptic potential was greatly augmented to give a paroxysmal depolarization shift and was reversibly blocked by 10 microM tiletamine. Our results show that tiletamine is a potent and reversible antagonist of NMA-mediated responses without itself having major effects in low concentrations on normal membrane and synaptic pyramidal cell properties.
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PMID:Tiletamine is a potent inhibitor of N-methyl-aspartate-induced depolarizations in rat hippocampus and striatum. 332 Mar 47

Flurothyl-induced status epilepticus was studied by light and electron microscopy (LM, EM) to determine the time course and structural features of neuronal necrosis in the vulnerable brain regions in epilepsy. The cerebral cortex, hippocampus and thalamus were examined after closely spaced recovery periods of up to 1 week. The results showed that acidophilic neurons appeared simultaneously in neurons of the neocortex, hippocampus and thalamus, and that this occurred within 1 h following the end of the epilepsy. The corresponding features of acidophilic neurons by EM were mitochondrial flocculent densities and large discontinuities in cell and nuclear membranes. Dark neurons were ubiquitous during the epilepsy, but recovered almost universally. A few dark neuronal forms persisted and underwent cytorrhexis after 12-h recovery or longer. Axon-sparing dendritic lesions characteristic of excitotoxic neuronal death were found in the neuropil of the neocortex, and in both vulnerable CA1 and resistant CA3 neurons of the hippocampus. Other than acute edema, glial changes were absent. The findings support an excitotoxic mechanism in epilepsy-induced selective neuronal necrosis also in brain regions outside the hippocampus, and contrast with previous reports in ischemia and hypoglycemia in that neuronal necrosis occurs virtually immediately after an epileptic insult. No "maturation" of cell damage, as described in ischemia, was seen. Furthermore, even exceedingly dark neuronal forms and massive dendritic swelling must be considered sub-lethal or prelethal cellular changes. Lethal cellular changes include acidophilia by LM, cell membrane breaks, and mitochondrial flocculent densities by EM.
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PMID:The nature and timing of excitotoxic neuronal necrosis in the cerebral cortex, hippocampus and thalamus due to flurothyl-induced status epilepticus. 336 60

Acute ischemia of the brain induces a cascade of biochemical and physiological events. The final consequences depend on the fact whether ischemia is of transient or permanent, total or partial nature. Alteration of extracellular potassium concentration, intracellular calcium and potassium concentration, development of cytotoxic and vasogenic edema, postischemic hyperfusion and no-reflow phenomenon are important factors which decide about the final fate of functional capacity. CO2 reactivity, autoregulation and hemorheology must be considered when therapeutic approaches are used to influence basic flow during ischemic condition. At present there exists no therapy which has been fully accepted and is able to guarantee benefit to the hypoperfused tissue. Since the calcium metabolism is altered by ischemic processes, substances which act on this metabolism might be of value in the treatment of ischemia and its consequences. However, their beneficial effect on cerebral infarction has not been proven yet. In subarachnoid hemorrhage and migraine calcium antagonists are used to prevent and treat ischemia. In epilepsia calcium overload blockers have been tried by one group with promising results.
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PMID:Is there a need for alternative approaches in the therapy of cerebrovascular disorders? 375 10


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