The Effect of Diazepam on Neonatal Seizure: In Vivo 31P and 1H NMR Study

Young, Richard S.; Chen, Benjamin; Petroff, Ognen A. C.; Gore, John C.; Cowan, Barrett E.; Novotny, Edward J.; Wong, Mabel; Zuckerman, Kaye

doi:10.1203/00006450-198901000-00006

Cited by 24 publications

(7 citation statements)

References 18 publications

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“…Whereas GABA antagonists induce rapid loss of phosphocreatine and glycogen, and large increases in lactate (~6–8-fold)—all signs of intense glycolytic activation [109-114], MSO-induced seizures do not produce such changes. Instead, levels of phosphocreatine and ATP are maintained at or near normal during MSO-induced seizures, while levels of glucose and glycogen are elevated, with only a modest rise in lactate (<twofold) [98].…”

Section: What Are the Metabolic And Functional Consequences Of Brain mentioning

confidence: 99%

Roles of Glutamine Synthetase Inhibition in Epilepsy

et al. 2012

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Glutamine synthetase (GS, E.C. 6.3.1.2) is a ubiquitous and highly compartmentalized enzyme that is critically involved in several metabolic pathways in the brain, including the glutamine-glutamate-GABA cycle and detoxification of ammonia. GS is normally localized to the cytoplasm of most astrocytes, with elevated concentrations of the enzyme being present in perivascular endfeet and in processes close to excitatory synapses. Interestingly, an increasing number of studies have indicated that the expression, distribution, or activity of brain GS is altered in several brain disorders, including Alzheimer’s disease, schizophrenia, depression, suicidality, and mesial temporal lobe epilepsy (MTLE). Although the metabolic and functional sequelae of brain GS perturbations are not fully understood, it is likely that a deficiency in brain GS will have a significant biological impact due to the critical metabolic role of the enzyme. Furthermore, it is possible that restoration of GS in astrocytes lacking the enzyme could constitute a novel and highly specific therapy for these disorders. The goals of this review are to summarize key features of mammalian GS under normal conditions, and discuss the consequences of GS deficiency in brain disorders, specifically MTLE.

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Section: What Are the Metabolic And Functional Consequences Of Brain mentioning

confidence: 99%

Roles of Glutamine Synthetase Inhibition in Epilepsy

et al. 2012

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“…In vivo 31 P MRS has been widely applied to study both normal and diseased brains and has led to a large number of publications (e.g., (19, 21–24, 26–28, 30–42). The abnormality in the HEP metabolites has been frequently observed in the diseased brains using in vivo 31 P MRS, and these changes or the change of HEP concentration ratios have been commonly applied in many clinical studies.…”

Section: Introductionmentioning

confidence: 99%

Advanced In Vivo Heteronuclear MRS Approaches for Studying Brain Bioenergetics Driven by Mitochondria

Zhu

Zhang

et al. 2009

Methods in Molecular Biology

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The greatest merit of in vivo magnetic resonance spectroscopy (MRS) methodology used in biomedical research is its ability for noninvasively measuring a variety of metabolites inside a living organ. It, therefore, provides an invaluable tool for determining metabolites, chemical reaction rates and bioenergetics, as well as their dynamic changes in the human and animal. The capability of in vivo MRS is further enhanced at higher magnetic fields because of significant gain in detection sensitivity and improvement in the spectral resolution. Recent progress of in vivo MRS technology has further demonstrated its great potential in many biomedical research areas, particularly in brain research. Here, we provide a review of new developments for in vivo heteronuclear 31P and 17O MRS approaches and their applications in determining the cerebral metabolic rates of oxygen and ATP inside the mitochondria, in both animal and human brains.

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“…The first appreciation of this was persistence of high lactate concentration in SE, leading to the pH,/lactate dissociation discussed above . In a study of flurothyl-induced SE in the neonatal dog, arrest of seizure discharge by diazepam restored PCr and Pi to control levels, whereas lactate remained elevated (Young et al, 1989). Brain lactate elevated by cortical electroshock causing less than 5 min of electrical afterdischarge declined slowly, reaching con-trol levels only after more than an hour (Prichard et al, 1987).…”

Section: Addition Of 'H Mrsmentioning

confidence: 96%

Nuclear Magnetic Resonance Spectroscopy of Seizure States

Prichard

1994

Epilepsia

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Magnetic resonance spectroscopy (MRS) can be used for noninvasive measurement of more than two dozen small metabolites in the brains of living animals and humans. In the first decade of its use for study of seizure phenomena in animals, MRS successfully detected in vivo seizure-induced cerebral acidosis and reduction of phosphocreatine concentration, changes that had been described previously by techniques requiring destruction of tissue. Thus validated, MRS was used to reveal new aspects of epileptic pathophysiology in animals: (a) dissociation of brain lactate and pH during experimental status epilepticus of low and intermediate intensity, reflecting metabolic compartmentation; and (b) long persistence of metabolically active elevated brain lactate after brief cortical electroshock. The latter phenomenon may be an extreme form of a mechanism by which lactate production primes synaptic terminals for maximal sustained firing rates during normal brain activation. Diffusion-weighted imaging of rat brain has shown that status epilepticus apparently shortens the mean path length of water diffusion, a novel finding that provides new insight concerning the physical conditions under which the seizure-related chemical changes detected by MRS occur. MRS study of epileptic patients has been undertaken more recently as instruments large enough for observations on humans have become available. Acidosis, reduction of phosphocreatine, and elevation of lactate have all been demonstrated in the human brain during seizure discharge. Chronic reduction of N-acetylaspartate in limbic regions probably reflects neuronal loss and may correlate with mesial temporal sclerosis.

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The Effect of Diazepam on Neonatal Seizure: In Vivo 31P and 1H NMR Study

Cited by 24 publications

References 18 publications

Roles of Glutamine Synthetase Inhibition in Epilepsy

Roles of Glutamine Synthetase Inhibition in Epilepsy

Advanced In Vivo Heteronuclear MRS Approaches for Studying Brain Bioenergetics Driven by Mitochondria

Nuclear Magnetic Resonance Spectroscopy of Seizure States

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