phosphocreatine and Seizures

To evaluate signal changes in the hippocampus of epileptic seizure rat models, based on quantified creatine chemical exchange saturation transfer (CrCEST) signals.. CEST data and. Measured CrCEST signals were exhibited significant differences between before and after KA injection in the ES group. At each time point, CrCEST signals showed significant correlations with PCr concentration (all |r| > 0.59; all P < 0.05); no significant correlations were found between CrCEST signals and tCr concentrations (all |r| < 0.22; all P > 0.05).. CrCEST can adequately detect changes in the concentration of Cr as a result of energy metabolism, and may serve as a potentially useful tool for diagnosis and assessment of prognosis in epilepsy.

Topics: Animals; Creatine; Disease Models, Animal; Image Processing, Computer-Assisted; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Rats, Wistar; Seizures

To investigate post-ictal changes in cerebral metabolites.. We performed a longitudinal quantitative proton magnetic resonance spectroscopy (MRS) study in 10 patients with epilepsy and 10 control subjects. The patients were studied on two occasions: immediately following a seizure, and on a second occasion at least 7h after the most recent seizure. Each study measured N-acetyl aspartate plus N-acetyl aspartyl glutamate (NAAt), Creatine plus phosphocreatine (Cr), Choline containing compounds (Cho) and glutamate plus glutamine (GLX) concentrations using a short-echo time sequence (TE=30ms), and NAAt, Cr and lactate using a second sequence with longer echo time (TE=144ms). The control group was studied on two occasions using the same sequences.. No inter-scan differences were observed for the control group. NAAt and NAAt/Cr levels were lower in the patient group at both measured TEs but did not change significantly between studies. The ratio of Cr at TE 144ms to TE 30ms (Cr(144)/Cr(30)) and GLX/Cr were higher and Cho lower in the post-ictal scan compared to the inter-ictal study. Change in Cr(144)/Cr(30) and NAAt(144)/Cr(144) correlated with the post-ictal interval. Lactate measurement at longer TE was not informative.. Proton MRS is sensitive to metabolite changes following epileptic seizures within the immediate post-ictal period. The ratio Cr(144)/Cr(30) is the most sensitive measure of metabolic disturbance and is highest in the post-ictal period but appears to normalise within 2h of the most recent seizure.

Topics: Adult; Aspartic Acid; Brain Chemistry; Choline; Creatine; Data Interpretation, Statistical; Dipeptides; Female; Glutamic Acid; Humans; Lactic Acid; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Protons; Seizures

Methylmalonic acidemias are metabolic disorders caused by a severe deficiency of methylmalonyl CoA mutase activity, which are characterized by neurological dysfunction, including convulsions. It has been reported that methylmalonic acid (MMA) accumulation inhibits succinate dehydrogenase (SDH) and beta-hydroxybutyrate dehydrogenase activity and respiratory chain complexes in vitro, leading to decreased CO2 production, O2 consumption and increased lactate production. Acute intrastriatal administration of MMA also induces convulsions and reactive species production. Though creatine has been reported to decrease MMA-induced convulsions and lactate production, it is not known whether it also protects against MMA-induced oxidative damage. In the present study we investigated the effects of creatine (1.2-12 mg/kg, i.p.) and MK-801 (3 nmol/striatum) on the convulsions, striatal content of thiobarbituric acid reactive substances (TBARS) and on protein carbonylation induced by MMA. Moreover, we investigated the effect of creatine (12 mg/kg, i.p.) on the MMA-induced striatal creatine and phosphocreatine depletion. Low doses of creatine (1.2 and 3.6 mg/kg) protected against MMA-induced oxidative damage, but did not protect against MMA-induced convulsions. A high dose of creatine (12 mg/kg, i.p.) and MK-801 (3 nmol/striatum) protected against MMA-induced seizures (evidenced by electrographic recording), protein carbonylation and TBARS production ex vivo. Furthermore, acute creatine administration increased the striatal creatine and phosphocreatine content and protected against MMA-induced creatine and phosphocreatine depletion. Our results suggest that an increase of the striatal high-energy phosphates elicited by creatine protects not only against MMA-induced convulsions, but also against MMA-induced oxidative damage. Therefore, since NMDA antagonists are limited value in the clinics, the present results indicate that creatine may be useful as an adjuvant therapy for methylmalonic acidemic patients.

Topics: Animals; Behavior, Animal; Creatine; Dizocilpine Maleate; Electrodes, Implanted; Electroencephalography; Male; Malonates; Microinjections; Neostriatum; Nerve Tissue Proteins; Neuroprotective Agents; Oxidative Stress; Phosphocreatine; Rats; Rats, Wistar; Seizures; Thiobarbituric Acid Reactive Substances

The present study has examined the effect of free radical spin trap N-tert-butyl-alpha-phenylnitrone (PBN) in the model of seizures induced in immature 12-day-old rats by bilateral intracerebroventricular infusion of dl-homocysteic acid (dl-HCA, 600 nmol/side). PBN was given i.p. in two doses (100 mg/kg each), 30 min prior and 30 min after dl-HCA infusion. PBN did not significantly influence the severity of seizures, evident both from the behavioral symptoms and EEG recordings. PBN normalized decreased ATP levels in the hippocampus, occurring during the acute phase of seizures ( approximately 45-50 min after infusion) and persisting until the end of the 24-h recovery period. PBN also led to normalization of decreased glucose levels and to a significant reduction of lactate accumulation in the cerebral cortex and hippocampus. The neuroprotective effect of PBN was evaluated after 24 h and 6 days of survival following dl-HCA-induced seizures (Nissl and Fluoro-Jade B staining). The administration of PBN resulted in a partial amelioration of severe damage observed in many brain regions following infusion of dl-HCA alone. The data suggest that increased free radical production is apparently occurring during seizures induced in immature rats by homocysteic acid. Free radical scavenger PBN had a clear-cut protective effect, evident as the improved recovery of brain energy status and as a partial, but significant, attenuation of neuronal degeneration associated with this model of seizures.

Topics: Adenosine Triphosphate; Animals; Brain; Cerebral Cortex; Disaccharides; Electroencephalography; Energy Metabolism; Free Radicals; Glucose; Glycogen; Hippocampus; Homocysteine; Injections, Intraperitoneal; Male; Neurons; Phosphocreatine; Rats; Rats, Wistar; Seizures; Spin Trapping

Methylmalonic acidemias are metabolic disorders caused by a severe deficiency of methylmalonyl-CoA mutase activity, which are characterized by neurological dysfunction, including convulsions. It has been reported that the accumulating metabolite, L-methylmalonic acid (MMA), inhibits succinate dehydrogenase leading to ATP depletion in vitro, and that the intrastriatal injection of MMA induces convulsions through secondary NMDA receptor stimulation. In this study we investigated the effect of creatine (1.2, 3.6 and 12.0 mg/kg, (i.p.), [DOSAGE ERROR CORRECTED] succinate (1.5 micromol/striatum) and MK-801 (3 nmol/striatum) on the convulsions and on the striatal lactate increase induced by MMA (4.5 micromol/striatum) in rats. The effect of creatine on the striatal phosphocreatine content and on MMA-induced phosphocreatine depletion was also evaluated. Creatine, succinate and MK-801 pretreatment decreased the number and duration of convulsive episodes and the lactate increase elicited by MMA. Creatine, but not succinate, prevented the convulsions and the lactate increase induced by the direct stimulation of NMDA receptors. Acute creatine administration increased the total striatal phosphocreatine content and prevented MMA-induced phosphocreatine depletion. Our results suggest that MMA increases lactate production through secondary NMDA receptor activation, and it is proposed that the anticonvulsant effect of creatine against MMA-induced convulsions may be due to an increase in the phosphocreatine content available for metabolic purposes.

Topics: Animals; Behavior, Animal; Corpus Striatum; Creatine; Disease Models, Animal; Dizocilpine Maleate; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Lactic Acid; Male; Methylmalonic Acid; N-Methylaspartate; Phosphocreatine; Radiation-Protective Agents; Rats; Rats, Wistar; Seizures; Succinic Acid

Perinatal hypoxia-ischemia (HI) is the most common precipitant of seizures in the first 24-48 h of a newborn's life. In a previous study, our laboratory developed a model of prolonged, continuous electrographic seizures in 10-day-old rat pups using kainic acid (KA) as a proconvulsant. Groups of animals included those receiving only KA, or HI for 15 or 30 min, followed by KA infusion. Our results showed that prolonged electrographic seizures following 30 min of HI resulted in a marked exacerbation of brain damage. We have undertaken studies to determine alterations in hippocampal high-energy phosphate reserves and the extracellular release of hippocampal amino acids in an attempt to ascertain the underlying mechanisms responsible for the damage promoted by the combination of HI and KA seizures.. All studies were performed on 10-day-old rats. Five groups were identified: (1) group I--KA alone, (2) group II--15 min of HI plus KA, (3) group III--15 min of HI alone, (4) group IV--30 min of HI plus KA, and (5) group VI--30 min of HI alone. HI was induced by right common carotid artery ligation and exposure to 8% oxygen/balance nitrogen. Glycolytic intermediates and high-energy phosphates were measured. Prior to treatment, at the end of HI (both 15 and 30 min), prior to KA injection, and at 1 (onset of seizures), 3, 5 (end of seizures), 7, 24 and 48 h, blood samples were taken for glucose, lactate and beta-hydroxybutyrate. At the same time points, animals were sacrificed by decapitation and brains were rapidly frozen for subsequent dissection of the hippocampus and measurement of glucose, lactate, beta-hydroxybutyrate, adenosine triphosphate (ATP) and phosphocreatine (PCr). In separate groups of rats as defined above, microdialysis probes (CMA) were stereotactically implanted into the CA2-3 region of the ipsilateral hippocampus for measurement of extracellular amino acid release. Dialysate was collected prior to any treatment, at the end of HI (15 and 30 min), prior to KA injection, and at 1 (onset of seizures), 3, 5 (end of seizures), 7 and 9 h. Determination of glutamate, serine, glutamine, glycine, taurine, alanine, and GABA was accomplished using high-performance liquid chromatography with EC detection.. Blood and hippocampal glucose concentrations in all groups receiving KA were significantly lower than control during seizures (p < 0.05). beta-Hydroxybutyrate values displayed the inverse, in that values were significantly higher (p < 0.01) in all KA groups compared with pretreatment controls during seizure activity. Values returned to control by 2 h following the cessation of seizures. Lactate concentrations in brain and blood mimicked those of beta-hydroxybutyrate. ATP values declined to 0.36 mmol/l in both the 15 and 30 min hypoxia groups compared with 1.85 mmol/l for controls (p < 0.01). During seizures, ATP and PCr values declined significantly below their homologous controls. Following seizures, ATP values only for those animals receiving KA plus HI for 30 min remained below their homologous controls for at least 24 h. Determination of amino acid release revealed elevations of glutamate, glycine, taurine, alanine and GABA above pretreatment control during HI, with a return to normal prior to KA injections. During seizures and for the 4 h of recovery monitored, only glutamate in the combined HI and KA group rose significantly above both the 15 min of HI plus KA and the KA alone group (p < 0.05).. Under circumstances in which there is a protracted depletion of high-energy phosphate reserves, as occurs with a combination of HI- and KA-induced seizures, excess amounts of glutamate become toxic to the brain. The latter may account for the exacerbation of damage to the newborn hippocampus, and serve as a target for future therapeutic intervention.

Topics: 3-Hydroxybutyric Acid; Adenosine Triphosphate; Animals; Animals, Newborn; Blood Glucose; Excitatory Amino Acid Agonists; Excitatory Amino Acids; Extracellular Space; Female; Glucose; Hippocampus; Hypoxia-Ischemia, Brain; Kainic Acid; Lactic Acid; Microdialysis; Phosphocreatine; Rats; Seizures; Telencephalon; Time Factors

Acute effects of seizure-inducing doses of the organophosphate compound diisopropylphosphorofluoridate (DFP, 1.25 mg/kg s.c.) or the carbamate insecticide carbofuran (CF, 1.25 mg/kg s.c.) on nitric oxide (NO) were studied in the brain of rats. Brain regions (pyriform cortex, amygdala, and hippocampus) were assayed for citrulline as the determinant of NO and for high-energy phosphates (ATP and phosphocreatine) as well as their major metabolites (ADP, AMP, and creatine). Rats, anesthetized with sodium pentobarbital (50 mg/kg i.p.), were killed using a head-focused microwave (power, 10 kW; duration, 1.7 s). Analyses of brain regions of controls revealed significantly higher levels of citrulline in the amygdala (289.8+/-7.0 nmol/g), followed by the hippocampus (253.8+/-5.5 nmol/g), and cortex (121.7+/-4.3 nmol/g). Levels of energy metabolites were significantly higher in cortex than in amygdala or hippocampus. Within 5 min of CF injection, the citrulline levels were markedly elevated in all three brain regions examined, while with DFP treatment, only the cortex levels were elevated at this time. With either acetylcholinesterase (AChE) inhibitor, the maximum increase in citrulline levels was noted 30 min post-injection (> 6- to 7-fold in the cortex, and > 3- to 4-fold in the amygdala or hippocampus). Within 1 h following DFP or CF injection, marked declines in ATP (36-60%) and phosphocreatine (28-53%) were seen. Total adenine nucleotides and total creatine compounds were reduced (36 58% and 28-48%, respectively). The inverse relationship between the increase in NO and the decease in high-energy phosphates, could partly be due to NO-induced impaired mitochondrial respiration leading to depletion of energy metabolites. Pretreatment of rats with an antioxidant, the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN, 200 mg/kg i.p.), prevented DFP- or CF-induced seizures, while the antioxidant vitamin E (100 mg/kg i.p. per day for 3 days) had no anticonvulsant effect. Both antioxidants, however, significantly prevented the increase of citrulline and the depletion of high-energy phosphates. It is concluded that seizures induced by DFP and CF produce oxidative stress due to a marked increase in NO, causing mitochondrial dysfunction, and thereby depleting neuronal energy metabolites. PBN pretreatment provides protection against AChE inhibitor-induced oxidative stress mainly by preventing seizures. Additional antioxidant actions of PBN may contribute to its pro

Topics: Adenosine Triphosphate; Amygdala; Animals; Antioxidants; Brain; Carbofuran; Cerebral Cortex; Cholinesterase Inhibitors; Citrulline; Cyclic N-Oxides; Hippocampus; Insecticides; Isoflurophate; Male; Neuroprotective Agents; Nitric Oxide; Nitrogen Oxides; Phosphocreatine; Rats; Rats, Sprague-Dawley; Seizures; Time Factors; Vitamin E

In cerebral gray matter, ATP concentration is closely maintained despite rapid, large increases in turnover and low substrate reserves. As seen in vivo by (31)P nuclear magnetic resonance (NMR) spectroscopy, brain ATP is stable early in seizures, a state of high energy demand, and in mild hypoxia, a state of substrate deficiency. Like other tissues with high and variable ATP turnover, cerebral gray matter has high phosphocreatine (PCr) concentration and both cytosolic and mitochondrial creatine kinase (UbMi-CK) isoenzymes. To understand the physiology of brain creatine kinases, we used (31)P NMR to study PCr and ATP regulation during seizures and hypoxia in mice with targeted deletion of the UbMi-CK gene. The baseline CK reaction rate constant (k) was higher in mutants than wild-types. During seizures, PCr and ATP decreased in mutants but not in wild-types. The k-value for the CK catalyzed reaction rate increased in wild-types but not in the mutants. Hypoxic mutants and wild-types showed similar PCr losses and stable ATP. During recovery from hypoxia, brain PCr and ATP concentrations returned to baseline in wild-types but were 20% higher than baseline in the mutants. We propose that UbMi-CK couples ATP turnover to the CK catalyzed reaction rate and regulates ATP concentration when synthesis is increased.

Topics: Acid Anhydride Hydrolases; Adenosine Triphosphate; Animals; Brain; Convulsants; Creatine Kinase; Creatine Kinase, Mitochondrial Form; Gene Expression Regulation, Enzymologic; Hypoxia, Brain; Immunohistochemistry; Isoenzymes; Magnetic Resonance Spectroscopy; Mice; Mice, Knockout; Mitochondria; Nucleoside-Triphosphatase; Pentylenetetrazole; Phosphocreatine; Seizures; Subcellular Fractions

To study the effects of creatine (Cr) on brain energy metabolism and on hypoxia-induced seizures, 5- to 30-day-old rabbit pups were given subcutaneous Cr (3 g/kg) for 3 days before exposure to 4% O2 for 8 min. In saline-treated controls, hypoxic seizures were most frequent at 15 days (80% of pups) and 20 days (60%) of age. Seizures were prevented at 15 days and reduced 60% at 20 days in Cr-treated pups. In surface coil-localized brain 31P nuclear magnetic resonance spectra, with signal from both cerebral gray (GM) and white (WM) matter, the phosphocreatine (PCr)/nucleoside triphosphate (NTP) ratio doubled between 5 and 30 days of age in controls. In all Cr-injected pups, brain PCr/NTP increased to values seen in 30-day-old controls. When spectra were acquired in predominantly GM and WM slices in vivo, the PCr/NTP ratio was very low in GM at 5 days but reached adult levels by 15 days in controls. In WM, the ratio increased steadily from 5 to 30 days of age. In Cr-injected pups, PCr/NTP increased to mature levels in WM and in GM at all ages. In conclusion, hypoxic seizures occur midway in the time course of brain PCr/NTP increase in rabbit pups as previously described in rat pups. In both altricial pups, systemic Cr increases brain PCr/NTP ratio and prevents hypoxic seizures. These results suggest that mature levels of PCr and/or Cr in brain limit EEG activation either directly or indirectly by preventing hypoxic metabolic changes.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Brain; Creatine; Electroencephalography; Energy Metabolism; Humans; Hypoxia, Brain; Injections, Subcutaneous; Magnetic Resonance Spectroscopy; Phosphocreatine; Rabbits; Seizures; Spasms, Infantile

The creatine kinase (CK) reaction is thought to be important in coupling ATP metabolism and regulating ADP concentration in tissues with high and variable ATP turnover, including cerebral gray matter (GM). There is low phosphocreatine (PCr), low CK reaction rates, and high mitochondrial CK (MiCK) isoenzyme activity in GM compared to white matter (WM). To compare the CK reaction in GM and WM when ATP metabolism is high, CK reactants and reaction rates were measured in predominantly GM and WM slices in vivo in 2 and 14-day old piglets during pentylenetetrazole (PTZ) seizures using 31P nuclear magnetic resonance (NMR) 1-dimensional chemical shift imaging (CSI). Arterial pressure, temperature, and blood gasses were stable at both ages. Before seizures, the PCr/nucleoside triphosphate (NTP) ratio was higher in WM than GM at both ages with a developmental increase seen in WM. The CK reaction rate constant increased in both regions between 2 and 14 days. During seizures, PCr/NTP increased in GM at 14 days due to increased PCr while the ratio and PCr decreased in WM. The NTP was more stable in WM and GM at both ages. The CK reaction rate decreased in both regions more at 2 than at 14 days. Thus, brain ATP, deduced from NTP, is stable during seizures in the piglet. In GM stable ATP is associated with a unique increase in PCR concentration.

Topics: Adenosine Triphosphate; Animals; Brain; Catalysis; Creatine Kinase; Magnetic Resonance Spectroscopy; Pentylenetetrazole; Phosphocreatine; Phosphorus; Seizures; Swine

Brain creatine kinase (CK) catalyzed phosphorus fluxes between phosphocreatine (PCr) and ATP and changes in reactant concentrations were measured using [31P] nuclear magnetic resonance spectroscopy ([31P]NMR) before and during pentylenetetrazole-induced seizures in 7 and 21 day old rats. The CK rate constants measured before seizures were three times higher in the older than in the younger rats. The rate constants increased 60% during seizures in the older rats but did not change or decreased in the younger. Small decreases in PCr were seen during seizures at both ages. A small decrease in ATP was seen at 7 days but not at 21 days.

Topics: Adenosine Triphosphate; Aging; Animals; Brain; Brain Chemistry; Creatine Kinase; Electroencephalography; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Pentylenetetrazole; Phosphocreatine; Rats; Seizures

Mitochondrial and cytosolic creatine kinase (CK) isozymes are active in cells with high and variable ATP metabolic rates. beta-Guanidinopropionic acid (GPA), a competitive inhibitor of creatine transport, was used to study the hypothesis that the creatine-CK-phosphocreatine (PCr) system is important in regulating brain ATP metabolism. The CK-catalyzed reaction rate and reactant concentrations were measured in vivo with 31P nuclear magnetic resonance spectroscopy during energy deficit (hypoxia) or high-energy turnover (seizures) states in urethane-anesthetized mice fed GPA, creatine, or standard chow (controls). Brain phosphagen (i.e., cellular energy reserves) or PCr plus phosphorylated GPA (GPAP) concentrations were equal. The phosphagen-to-NTP ratio was lower than in controls. In vivo CK reaction rate decreased fourfold, whereas ex vivo CK activity that was biochemically measured was doubled. During seizures, CK-catalyzed fluxes increased only in GPA-fed mice. Phosphagen increased in GPA-fed mice, whereas PCr decreased in controls. Survival was higher and brain phosphagen and ATP losses were less for hypoxic GPA-fed mice than for controls. In contrast to mice fed GPA, hypoxic survival and CK reactant concentrations during hypoxia and seizures were the same in creatine-fed mice and controls. Thus GPA, GPAP, or adaptive changes in ATP metabolism stabilize brain ATP and enhance survival during hypoxia in mice.

Topics: Adenosine Triphosphate; Animals; Brain; Creatine; Creatine Kinase; Diet; Female; Guanidines; Hypoxia; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred Strains; Phosphocreatine; Phosphorylation; Propionates; Seizures

The present study was undertaken to explore how transient ischemia in rats alters cerebral metabolic capacity and how postischemic metabolism and blood flow are coupled during intense activation. After 6 h of recovery following transient forebrain ischemia 15 min in duration, bicuculline seizures were induced, and brains were frozen in situ after 0.5 or 5 min of seizure discharge. At these times, levels of labile tissue metabolites were measured, whereas the cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) were measured after 5 min of seizure activity. After 6 h of recovery, and before seizures, animals had a 40-50% reduction in CMRO2 and CBF. However, because CMRO2 rose three-fold and CBF fivefold during seizures, CMRO2 and CBF during seizures were similar in control and postischemic rats. Changes in labile metabolites due to the preceding ischemia encompassed an increased phosphocreatine/creatine ratio, as well as raised glucose and glycogen concentrations. Seizures gave rise to minimal metabolic perturbation, essentially comprising reduced glucose and glycogen contents and raised lactate concentrations. It is concluded that although transient ischemia leads to metabolic depression and a fall in CBF, the metabolic capacity of the tissue is retained, and drug-induced seizures lead to a coupled rise in metabolic rate and blood flow.

Topics: Animals; Bicuculline; Cerebrovascular Circulation; Creatine; Energy Metabolism; Glucose; Glycogen; Ischemic Attack, Transient; Kinetics; Male; Oxygen; Phosphocreatine; Prosencephalon; Rats; Rats, Wistar; Seizures

The cerebral metabolic changes elicited by kainate-induced seizures in the rat were investigated by in vivo combined NMR spectroscopy of 31P and 1H. Systemic injection of kainate induced no significant changes in cerebral ATP or PCr levels during up to 90 min of continuous, generalised seizures, and the cerebral 31P spectra showed only a transient mild cerebral acidosis 30 min after kainate administration. In parallel with the changes in intracellular cerebral pH, the 1H spectra showed a significant increase in lactate, which remained elevated throughout the seizures. These findings indicate that oxidative metabolism does not completely match the increased glycolysis during seizures though the energy homeostasis is maintained. This suggests that oxidative metabolism has a limited capacity to satisfy the brain's energy needs during the kainate-induced seizures, but that the different pathways of energy production in the brain cells can overcome this limitation. Thus the brain damage associated with this experimental model of epilepsy is not due to extended major failure of the energy supply.

Topics: Acidosis; Adenosine Triphosphate; Animals; Blood Pressure; Brain; Carbon Dioxide; Energy Metabolism; Fourier Analysis; Glycolysis; Homeostasis; Hydrogen; Hydrogen-Ion Concentration; In Vitro Techniques; Kainic Acid; Lactates; Magnetic Resonance Spectroscopy; Oxygen; Partial Pressure; Phosphocreatine; Phosphorus; Rats; Seizures; Time Factors

Seizures were induced in 7-day-old rats by intraperitoneal injection of DL-homocysteine thiolactone. Phosphocreatine (PCr), ATP, glucose, glycogen and lactate were determined in the cerebral cortex during various intervals after injection, corresponding to the early, as well as long periods of seizure activity. The unchanged levels of ATP, a very mild PCr decline and a pronounced accumulation of lactate (in the face of modest changes in brain glucose and glycogen) were observed. These results suggest that the immature rat brain is able to compensate energy expenditure associated with seizure activity by increased energy production, mainly due to increased anaerobic glycolysis. It remains to be determined whether a similar conclusion is also valid for other brain regions, e.g. subcortical structures.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Cerebral Cortex; Energy Metabolism; Glucose; Glycogen; Homocysteine; Lactates; Lactic Acid; Male; Phosphocreatine; Rats; Rats, Wistar; Seizures

Seizures were induced in 7-day-old rats by intraperitoneal injection of DL-homocysteine thiolactone. Phosphocreatine (PCr), ATP, glucose, glycogen and lactate were determined in the cerebral cortex during various intervals after injection, corresponding to the early, as well as long periods of seizure activity. The unchanged levels of ATP, a very mild PCr decline and a pronounced accumulation of lactate (in the face of modest changes in brain glucose and glycogen) were observed. These results suggest that the immature rat brain is able to compensate energy expenditure associated with seizure activity by increased energy production, mainly due to increased anaerobic glycolysis. It remains to be determined whether a similar conclusion is also valid for other brain regions, e.g. subcortical structures.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Cerebral Cortex; Energy Metabolism; Glucose; Glycogen; Homocysteine; Lactates; Male; Phosphocreatine; Rats; Rats, Wistar; Seizures

31-P magnetic resonance spectroscopy (MRS) allows noninvasive measurements of cerebral phosphorus compounds: ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME) and phosphodiesters (PDE). In this paper we reported our MRS data from the brains of infants with intrauterine growth retardation, respiratory distress syndrome, neonatal seizures or neonatal asphyxia, and discussed the possibilities to prevent brain damage due to these perinatal troubles.

Topics: Adenosine Triphosphate; Asphyxia; Brain; Energy Metabolism; Fetal Growth Retardation; Humans; Infant, Newborn; Magnetic Resonance Spectroscopy; Phosphocreatine; Respiratory Distress Syndrome, Newborn; Seizures

The hippocampus exhibits a post-ictal phenomenon in which it is unresponsive to further stimulation. It has been suggested that this loss of excitability is the basis of post-seizure amnesia. The biochemical events associated with this phenomenon are unclear. In the present study, energy metabolites were measured in the stratum oriens, stratum pyramidale and stratum radiatum in rat hippocampus, and correlated with field potential recordings. Wistar rats were anesthetized and the calvarium removed. Following removal of the cortex by aspiration, the hippocampus was covered with oil, and stimulating and recording electrodes were placed. Stimulation consisted of a train of stimuli at 100 Hz (10-20 m Amps). This stimulation was found to be effective in evoking self-sustaining after-discharges and post-ictal depression. Tissues for metabolite analysis were taken from a series of controls, from animals during active self-sustaining seizures, and from animals which were totally unresponsive to further electrical stimulation. Hippocampal tissue for metabolite analysis was obtained by pouring liquid N2 on the exposed tissue, then removing the frozen tissue. Glucose, ATP, and phosphocreatine were measured in hippocampal layers of CA1 using fluorescence techniques and enzymatic cycling. Results showed that during seizure activity, glucose, ATP, and phosphocreatine were all decreased from 40-80% in the three layers of the hippocampus, whereas from 60 seconds after the onset of hippocampal shutdown, energy metabolites had returned toward normal. Thus, at a time when the hippocampus was unresponsive, energy metabolites were at control levels. These data suggest that the shutdown phenomenon occurs in the presence of adequate energy stores.

Topics: Animals; Energy Metabolism; Glucose; Hippocampus; Male; Phosphocreatine; Rats; Rats, Inbred Strains; Refractory Period, Electrophysiological; Seizures

It is assumed that when anticonvulsants arrest seizure, there is rapid return of brain high energy phosphates and brain lactate to control values. To test this hypothesis, diazepam was administered to neonatal dogs during flurothyl-induced seizure. In vivo 31P nuclear magnetic resonance spectroscopy disclosed that diazepam quickly arrested electrographic seizure and restored brain phosphocreatine and inorganic phosphate to baseline values. In contrast, in vivo 1H nuclear magnetic resonance spectroscopic measurements showed that arrest of seizure with diazepam did not return brain lactate to control values. The sustained increase in cerebral blood flow and prolonged elevation of brain lactate, acetate, valine, and succinate in the postictal period indicate that metabolic recovery of the brain occurs over an extended period of time after the normalization of EEG, phosphocreatine, and brain pH.

Topics: Acetates; Animals; Animals, Newborn; Blood Glucose; Blood Pressure; Brain; Diazepam; Dogs; Electroencephalography; Glucose; Hydrogen-Ion Concentration; Lactates; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Random Allocation; Seizures; Succinates; Valine

Cats were subjected to a 3.5-atm fluid percussion impact administered to the cerebral cortex. Near-infrared spectrophotometry (NIRS) was used to measure the quantity of oxyhemoglobin and total hemoglobin in the illuminated tissue as well as the cytochrome a, a3 redox state. Corroborative data were obtained by freezing brains with liquid nitrogen and measuring cortical concentrations of ATP, creatine phosphate (CP), and lactate. Immediately postimpact there was a rise in mean arterial pressure with a 38% increase of highly oxygenated blood and a shift toward oxidation in the cytochrome a, a3 redox state. By 4 hours postimpact, cytochrome a, a3 was becoming progressively reduced despite the persistence of hyperemia. This was associated with a significant (p less than 0.01) decrease in ATP and CP concentration. Additional studies in which a 0.5-sec, 100-v electrical seizure was induced before and after fluid percussion demonstrated significant differences in seizure response, indicating a failure of autoregulation.

Topics: Adenosine Triphosphate; Animals; Brain Chemistry; Brain Injuries; Cats; Electron Transport Complex IV; Hemoglobins; Homeostasis; Lactates; Oxidation-Reduction; Oxyhemoglobins; Phosphocreatine; Seizures; Spectrophotometry, Infrared

The cerebral metabolic response to bicuculline (BC)-induced status epilepticus (SE) was studied in two-week-old ketamine-anesthetized marmoset monkeys. During 30-min clonic seizures, mean blood pressure, plasma glucose and paO2 did not decrease and plasma lactate doubled. Brains were funnel-frozen and punch biopsies of frontoparietal cortex, temporal cortex and thalamus were analyzed for ATP, phosphocreatine (PCr), glucose and lactate. There were marked reductions of ATP (to 56-77% of controls), PCr (to 23-28% of controls) and glucose (to 1-4% of controls), and lactate increased 3- to 6-fold in seizure animals. NADH fluorescence increased during seizures in cerebral cortex, thalamus, amygdaloid nuclei, hippocampus, posterior striatum and hemispheric white matter. This suggests a reduced tissue redox state in these regions and is correlated with the high energy phosphate depletion and elevated lactate in cortex and thalamus. Our results demonstrate a significant depletion of energy reserves and glucose in cerebral cortex and thalamus during neonatal seizures in the absence of adverse systemic factors. These seizure-induced metabolic changes in brain could have adverse long-term effects on brain development and function.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Bicuculline; Brain; Callitrichinae; Energy Metabolism; Glucose; Lactates; Lactic Acid; NAD; Phosphocreatine; Seizures

In vivo [31P] nuclear magnetic resonance (NMR) spectroscopy disclosed that a 10 second electroshock seizure in oxygenated neonatal dogs produced prolonged alteration of brain phosphocreatine (PCr), inorganic phosphate (Pi), and lactate. The slow return of these metabolites to baseline may be related to lower endogenous stores of high energy phosphates, or less developed pathways for their regeneration.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Brain; Dogs; Electroshock; Energy Metabolism; Lactates; Lactic Acid; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Seizures

In order to assess the early regional changes in energy metabolism in bicuculline induced seizures, mice were injected and sacrificed before the onset of overt seizure activity, and shortly after clonic-tonic seizures began. The energy metabolites glucose, ATP, and phosphocreatine were measured in layers of the motor cortex and the cerebellar vermis. Results showed minimal metabolite changes in the cerebellum, whereas changes in energy metabolism in the motor cortex were largely localized to the layers containing pyramidal cells. These results are in agreement with previous studies showing a relative sparing of the cerebellum, and suggest early cortical changes occur in pyramidal cells.

Topics: Adenosine Triphosphate; Animals; Bicuculline; Cerebellum; Energy Metabolism; Female; Glucose; Mice; Motor Cortex; Phosphocreatine; Seizures

In vivo phosphorus 31 nuclear magnetic resonance (31P NMR) spectroscopy was used to evaluate changes in cerebral high-energy phosphate compounds in 8 infants with seizures. During the study 4 babies had seizures that caused a 50% decrease in the phosphocreatine to inorganic phosphate (PCr/Pi) ratio. Focal seizures caused lateralized decreases in the PCr/Pi ratio; generalized seizures caused bilateral decreases. Postictal spectra had increased PCr/Pi ratios, presumably due to postictal inhibition. Interictal 31P NMR spectra were normal. One patient's seizures were successfully treated with intravenously administered phenobarbital during NMR data acquisition, causing an immediate increase in the PCr/Pi ratio from 0.7 to 1.2. These studies indicate that cerebral PCr concentration decreases by approximately 33% and that oxidative metabolism increases by approximately 45% during neonatal seizures. Five babies had PCr/Pi ratios of less than 0.8 during seizures and subsequently developed long-term neurological sequelae, which suggests that neonatal seizures may cause or exacerbate cerebral injury by increasing cerebral metabolic demands above energy supply.

Topics: Adenosine Triphosphate; Anticonvulsants; Cerebral Cortex; Electroencephalography; Humans; Infant; Infant, Newborn; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Seizures

Female chicks carrying the lethal, sex-linked recessive paroxysmal (px) gene are susceptible to spontaneous and audiogenic seizures. Because seizure activity does not begin until 1 to 2 weeks posthatching - coincidental with disappearance of the yolk-sac - it is postulated that a contributing factor to seizure activity may be a developmental failure of the chick's ability to switch from lipid to carbohydrate as a primary energy source. In testing this hypothesis, three experiments were performed: 1) to evaluate cerebral energy reserves - adenosine triphosphate (ATP), phosphocreatine - of px and normal chicks; 2) to determine effects of energy source (ethanol, glucose, insulin, and glucose-insulin combined) on audiogenically-induced seizure activity and electrical seizure threshold; 3) to evaluate energy source utilization as estimated by the respiratory quotient (RQ). Brain ATP and phosphocreatine levels in px chicks were both decreased (P less than .05) as early as 10 days posthatching. Ethanol increased electrical seizure threshold in 50% of px chicks and provided protection from audiogenic stimulation. No consistent effect was found with any of the other substances. The RQ of px chicks were lower (P less than .05) than those of controls by 18 days posthatching.

Topics: Acoustic Stimulation; Adenosine Triphosphate; Animals; Brain; Chickens; Energy Metabolism; Ethanol; Female; Genes, Recessive; Glucose; Insulin; Male; Phosphocreatine; Poultry Diseases; Seizures

The effects of prolonged bicuculline-induced seizures on cerebral blood flow and metabolism were determined in paralyzed, mechanically ventilated neonatal dogs. Transient changes occurring early in the course of status epilepticus included significant arterial hypertension, hypocarbia, elevation of plasma norepinephrine levels, and decline in brain glucose concentration. Cerebral blood flow remained elevated throughout the 45 minutes of seizure. Determination of cerebral metabolite values by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy and by in vitro enzymatic analysis of frozen brain samples showed significant decreases in the level of phosphocreatine and relatively less change in ATP values. Progressive intracellular acidosis occurred, coincident with elevation of brain lactate concentrations. We conclude that the physiological and metabolic alterations that occur during prolonged seizures are not uniform, but change with time. Any hypothesis advanced to explain the mechanism of neuronal injury during prolonged seizures must take into account these temporally related changes.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Brain; Cerebrovascular Circulation; Dogs; Electroencephalography; Magnetic Resonance Spectroscopy; Phosphocreatine; Phosphorus; Seizures; Time Factors

Audiogenic seizure-prone mice (DBA/2J) were exposed to a broad band noise source. A reproducible response consisting of wild run, clonus, and tonic stages resulted in all mice. Layers 1 and pyramidal from the parietal cortex and the molecular and Purkinje cell-rich layers from the cerebellar vermis were separately analyzed for glucose, glycogen, ATP, and phosphocreatine. Results showed a biphasic cerebellar response, with decreases in high energy phosphates occurring during the wild run and tonic stage. In the cortex, similar changes occurred in the pyramidal cell layer, but the decreases were not as pronounced as those in the cerebellum. Cells from layer 1 of the parietal cortex were not affected as much as those of the pyramidal layer, suggesting a differential effect between neuronal and nonneuronal cell populations. The greater response of the cerebellum could indicate an attempt to reduce the severity of both the wild run and the tonic extension seizure.

Topics: Acoustic Stimulation; Adenosine Triphosphate; Animals; Cerebellum; Cerebral Cortex; Clonazepam; Energy Metabolism; Female; Glucose; Glycogen; Mice; Mice, Inbred DBA; Phosphocreatine; Seizures; Valproic Acid

Isoniazid is a useful chemical convulsant in that metabolic events associated with the preseizure state can be easily examined. In the present study, net levels of glucose, glycogen, ATP, and phosphocreatine were measured using enzymatic techniques in control mice, and in those injected with isoniazid. Results from this study showed a differential effect of isoniazid on cells from the cerebral cortex and the cerebellum. In the preseizure stage, the high energy phosphates ATP and phosphocreatine were decreased in layer 1 and the pyramidal cell layer of the cerebral parietal cortex, but were unchanged in the cerebellum. At the onset of seizures, metabolites were decreased not only in cortical layers, but in the molecular layer and Purkinje cell rich layer of the cerebellum as well. The somewhat delayed response of the cerebellum emphasizes the differential nature of metabolism in various brain regions. Such a delay in cerebellar energy response to perturbation may be conducive to the seizure state. In another series of mice, either sodium valproate or clonazepam was administered prior to isoniazid, and metabolite studies repeated. Results showed that at a time when each anticonvulsant acted to eliminate overt seizure activity, the reduction in ATP and phosphocreatine was not as great as it was in seizing mice treated with isoniazid alone.

Topics: Adenosine Triphosphate; Animals; Cerebellar Cortex; Cerebral Cortex; Clonazepam; Energy Metabolism; Female; Glucose; Glycogen; Isoniazid; Mice; Phosphocreatine; Seizures; Valproic Acid

Pentylenetetrazole was administered to Swiss-Albino mice, producing clonic-tonic seizures. Other groups were pretreated with one of the three anticonvulsants: phenytoin, clonazepam, or sodium valproate. Mice were sacrificed during the preseizure (1 minute) stage and at the onset of clonic-tonic seizures (2 minutes). Glucose, glycogen, ATP, and phosphocreatine were measured in layers of the parietal cortex and cerebellar vermis. Cortical metabolites were unchanged, or increased slightly, suggesting decreased utilization. In both cerebellar layers, glucose and glycogen were significantly decreased, and phosphocreatine was decreased in the molecular layer. These results indicate a regionally selective effect for pentylenetetrazole on cerebral energy metabolites. Pretreatment with anti-convulsants reduced the severity of the seizure, and eliminated the effect of pentylenetetrazole on glucose and glycogen.

Topics: Adenosine Triphosphate; Animals; Behavior, Animal; Blood Glucose; Cerebellum; Energy Metabolism; gamma-Aminobutyric Acid; Glycogen; Muridae; Parietal Lobe; Pentylenetetrazole; Phosphocreatine; Purkinje Cells; Seizures

Topics: Acoustic Stimulation; Adenosine Triphosphate; Aging; Animals; Brain; Glucose; Glycogen; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Phosphocreatine; Seizures; Species Specificity

Topics: Adenosine Triphosphate; Animals; Brain; Cyclic AMP; Cyclic GMP; Electroshock; gamma-Aminobutyric Acid; Glucose; Glycogen; Kinetics; Lactates; Male; Mice; Phenytoin; Phosphocreatine; Purkinje Cells; Seizures

Experimental seizures were induced in mice by application of 50 mA for 0.2 sec via corneal electrodes. The reproducible conclusive behavior was characterized by a sequence of 2 sec of tonic flexion, 13 sec of tonic extension, and 8 sec of clonus followed by a postictal depressive stage. The animals were frozen and tissues were prepared for analysis according to Lowry and Passonneau [Lowry, O. H. & Passonneau, J. V. (1972) A Flexible System of Enzymatic Analysis (Academic, New York)]. Freeze-dried samples (1-10 ng) of pyramidal cell bodies and adjacent neuropil from the parietal cortex and of Purkinje cell bodies and adjacent neuropil from the cerebellum were analyzed for glucose, ATP, and P-creatine (0.01-0.05 pmol). There were marked decreases in these energy stores after the maximal electroshock in three of the areas examined. In the Purkinje cell bodies, however, the metabolic stress was dampened; glucose concentrations decreased, but the levels of ATP were maintained and, to a lesser extent, those of P-creatine. The results indicate that the output from the Purkinje cells is less than in the other regions examined in the excitable stages of the convulsion. The lesser energy debt probably reflects lower energy demand as well as a lower discharge intensity. The fact that Purkinje cells are spared from the metabolic stress imposed on other regions may be a partial explanation of the seizure activity. A diminished output from the Purkinje cells could be a situation that permits cortical convulsive activity.

Topics: Adenosine Triphosphate; Animals; Cerebellum; Cerebral Cortex; Electric Stimulation; Glucose; Mice; Phosphocreatine; Purkinje Cells; Seizures

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Bicuculline; Cerebral Cortex; Energy Metabolism; Kinetics; Lactates; Male; Phosphocreatine; Rats; Seizures

Topics: Adenine Nucleotides; Amino Acids; Ammonia; Animals; Bicuculline; Biological Transport; Brain; Citric Acid Cycle; Creatine; Energy Metabolism; Glucose; Glycolysis; Hydrogen-Ion Concentration; Male; NAD; Oxidation-Reduction; Phosphocreatine; Rats; Seizures

Topics: 3-Mercaptopropionic Acid; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Cerebral Cortex; Energy Metabolism; Glucose; Glycogen; Homocysteine; Lactates; Male; Mice; Phenobarbital; Phosphocreatine; Seizures; Sulfhydryl Compounds

Topics: Adenine Nucleotides; Animals; Blood Pressure; Brain; Creatine Kinase; Electroencephalography; Electroshock; Energy Metabolism; Flurothyl; Glucose; Glycogen; Hydrogen-Ion Concentration; L-Lactate Dehydrogenase; Lactates; Male; Mice; NAD; Oxidation-Reduction; Pentylenetetrazole; Phosphocreatine; Rats; Seizures

Topics: Acidosis; Adenosine Diphosphate; Adenosine Triphosphate; Animals; Bicarbonates; Blood Flow Velocity; Brain; Carbon Dioxide; Cats; Cerebrovascular Circulation; Dogs; Electric Stimulation; Energy Metabolism; Epilepsy; Flurothyl; Hydrogen-Ion Concentration; Lactates; Mice; NAD; Oxygen; Oxygen Consumption; Pentylenetetrazole; Phosphocreatine; Pyruvates; Rats; Seizures

Topics: Adenosine Triphosphate; Animals; Brain; Circadian Rhythm; Disulfiram; Glucose; Lactates; Male; Mice; Mice, Inbred Strains; Oxygen; Phosphocreatine; Pressure; Pyruvates; Seizures; Time Factors

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Blood Glucose; Carbon Dioxide; Cerebral Cortex; Creatine; Electroencephalography; Fasting; Hydrogen-Ion Concentration; Hypoglycemia; Insulin; Male; Oxygen; Phosphocreatine; Rats; Seizures; Time Factors

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Blood Glucose; Cerebral Cortex; Electrochemistry; Energy Metabolism; Glucose; Glycogen; Homocysteine; Humans; Lactates; Lactones; Mice; Phosphocreatine; Seizures

Topics: Adenosine Triphosphate; Animals; Biological Transport, Active; Brain; Cerebral Cortex; Energy Metabolism; Membrane Potentials; Mitochondria; NAD; NADP; Neurons; Oxidative Phosphorylation; Oxidoreductases; Phosphocreatine; Potassium; Rabbits; Rats; Seizures; Sodium

Topics: Adenosine Triphosphate; Animals; Brain; Carbon Dioxide; Cerebrovascular Circulation; Disease Models, Animal; Electric Stimulation; Electroencephalography; Electroshock; Energy Metabolism; Evoked Potentials; Lactates; Oxygen; Oxygen Consumption; Partial Pressure; Pentylenetetrazole; Phosphocreatine; Rats; Seizures

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Brain Chemistry; Guanine Nucleotides; Inosine Nucleotides; Mice; NAD; Nucleotides; Phosphocreatine; Seizures; Sound; Time Factors; Uracil Nucleotides

Topics: Acetates; Acoustic Stimulation; Adenine Nucleotides; Adenosine Diphosphate; Animals; Brain; Brain Chemistry; Injections, Intramuscular; Mice; Nitrogen; Oxidative Phosphorylation; Phosphocreatine; Seizures

Topics: Adenosine Triphosphate; Animals; Brain Stem; Central Nervous System; Cerebellum; Cerebral Cortex; Electroshock; Glucose; Glycogen; Lactates; Male; Mice; Phenobarbital; Phosphocreatine; Seizures; Spinal Cord; Thalamus

Topics: Adenosine Triphosphate; Animals; Brain Stem; Central Nervous System; Cerebellum; Cerebral Cortex; Citric Acid Cycle; Glucose; Glycogen; Glycolysis; Hexosephosphates; Ketoglutaric Acids; Lactates; Malates; Male; Mice; Phosphocreatine; Seizures; Spinal Cord; Thalamus

Topics: Acetates; Acoustic Stimulation; Adenine Nucleotides; Adenosine Diphosphate; Adenosine Triphosphate; Aminobutyrates; Animals; Anticonvulsants; Brain; Guinea Pigs; Phosphocreatine; Seizures

Topics: Adenine Nucleotides; Adenosine Triphosphate; Ammonia; Animals; Brain; Cerebellum; Cerebral Cortex; Citric Acid Cycle; Medulla Oblongata; Nerve Tissue Proteins; Oxidative Phosphorylation; Oxidoreductases; Oxygen Consumption; Pentylenetetrazole; Phosphocreatine; Rats; Seizures

Topics: Adenosine Triphosphate; Animals; Brain; Brain Chemistry; Fluorometry; Freezing; Glucose; Glycogen; Hypoxia; Ischemia; Lactates; Male; Mice; Phosphocreatine; Seizures; Time Factors

Topics: Adenosine Triphosphate; Animals; Central Nervous System Stimulants; Cerebral Cortex; Energy Transfer; Ethers; Fluorine; Freezing; Glucose; Hindlimb; Lactates; Male; Mice; Myoclonus; Phosphocreatine; Seizures

Topics: Animals; Brain Chemistry; Electroshock; Glucose; Hexokinase; Hexosephosphates; Lactates; Pentylenetetrazole; Phosphocreatine; Rats; Seizures; Ultrasonics

Topics: Adenine Nucleotides; Adenosine Triphosphate; Amino Acids; Aminobutyrates; Animals; Brain; Centrifugation; Citrates; Fluorometry; Freezing; Glucose; Glutamates; Glycogen; Lactates; Male; Metabolism; Pentylenetetrazole; Phosphates; Phosphocreatine; Pyruvates; Rats; Seizures; Spectrophotometry; Spectrum Analysis

Topics: Adenosine Triphosphate; Animals; Brain; Electroencephalography; Electroshock; Glycolysis; Hydrogen-Ion Concentration; Lactates; Mice; Paralysis; Phosphocreatine; Seizures

Topics: Acetylcholinesterase; Adenosine Triphosphate; Amino Acids; Aminobutyrates; Animals; Brain; Chromatography, Paper; Disease Models, Animal; Glucose; Glycogen; Lactates; Oxygen Consumption; Phosphates; Phosphocreatine; Plant Extracts; Propionates; Rats; Seizures; Toxins, Biological

Topics: Adenosine Triphosphate; Animals; Brain; Glucose; Glycogen; Lactates; Methionine; Methionine Sulfoximine; Mice; Phosphocreatine; Seizures

Topics: Adenosine Triphosphate; Animals; Brain; Electroshock; Glucose; Lactates; Mice; Oxygen; Paralysis; Phosphocreatine; Respiration, Artificial; Seizures

Topics: Adenosine Triphosphate; Animals; Anticonvulsants; Brain Chemistry; Cerebral Cortex; Electroshock; Glucose; Lactates; Mice; Phenobarbital; Phenytoin; Phosphocreatine; Seizures; Trimethadione

Topics: Adenosine Triphosphate; Animals; Brain; Brain Chemistry; Calcium; Electric Stimulation; Glucose; Lactates; Lithium; Magnesium; Mice; Ouabain; Phosphocreatine; Potassium; Seizures; Sodium

Topics: Adenosine Triphosphate; Ammonia; Animals; Brain; Cerebellum; Cerebral Cortex; Glucose; Glutamates; Glycogen; Lactates; Male; Methionine Sulfoximine; Methods; Phosphocreatine; Rats; Seizures; Time Factors

Topics: Animals; Centrifugation; Cerebral Cortex; Chlorpromazine; Electric Stimulation; Electroshock; Freezing; Glucose; Glycogen; Hypoxia; Insulin; Lactates; Male; Mice; Pentylenetetrazole; Phenobarbital; Phosphocreatine; Secobarbital; Seizures; Stress, Physiological

Topics: Adenine Nucleotides; Animals; Aspartic Acid; Brain; Brain Chemistry; Central Nervous System Stimulants; Citrates; Glutamates; Glycogen; Glycolysis; Hexokinase; Hexosephosphates; In Vitro Techniques; Lactates; Mice; Phosphocreatine; Phosphofructokinase-1; Seizures

Topics: Adenosine Triphosphate; Adrenal Glands; Ammonia; Animals; Ascorbic Acid; Brain Chemistry; Hexosephosphates; Lactates; Noise; Phosphocreatine; Rats; Seizures

Topics: Acetylcholine; Animals; Brain Chemistry; In Vitro Techniques; Phosphocreatine; Rats; Seizures