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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of intravenously administered lidocaine on the cerebral cortical energy state and glycolytic metabolism were studied in rats. In one series, rats were divided into five groups according to EEG patterns, i.e., control, desynchronized, synchronized, seizure (1-min duration) and recovery groups. With lidocaine infusion (0.75 mg/min), there were no significant changes from the control group in the cerebral energy state except for a modest increase in phosphocreatine (PCr) in the seizure group and a small decrease in ADP in the non-seizure groups. The cerebral energy charge remained unchanged. Lactate and pyruvate significantly decreased in the non-seizure groups. In a second series, rats were divided into five groups, i.e., control, lidocaine seizure groups (5-min duration, 1.5 mg/min) at hypocapnia, normocapnia and hypercapnia, and a bicuculline (1.2 mg/kg) seizure group. The metabolic changes during lidocaine seizure were essentially the same as those observed in the seizure group in the first series. However, the increase in PCr during lidocaine seizure was significant only in the hypocapnic and the normocapnic groups. Bicuculline-induced seizures were accompanied by a significant decrease in high energy phosphates. In summary, neither a non-seizure nor-seizure dose of lidocaine caused any reduction in the cerebral energy charge nor was there any evidence of increased anaerobic metabolism in the cerebral cortex during lidocaine-induced seizures.
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PMID:Cerebral energy state and glycolytic metabolism during lidocaine infusion in the rat. 721 27

The objective of the present experiments was to study metabolic correlates to the localization of neuronal lesions during sustained seizures. To that end, status epilepticus was induced by i.v. administration of bicuculline in immobilized and artificially ventilated rats, since this model is known to cause neuronal cell damage in cerebral cortex and hippocampus but not in the cerebellum. After 20 or 120 min of continuous seizure activity, brain tissue was frozen in situ through the skull bone, and samples of cerebral cortex, hippocampus, and cerebellum were collected for analysis of glycolytic metabolites, phosphocreatine (PCr), ATP, ADP, AMP, and cyclic nucleotides. After 20 min of seizure activity, the two "vulnerable" structures (cerebral cortex and hippocampus) and the "resistant" one (cerebellum) showed similar changes in cerebral metabolic state, characterized by decreased tissue concentrations of PCr, ATP, and glycogen, and increased lactate concentrations and lactate/pyruvate ratios. In all structures, though, the adenylate energy charge remained close to control. At the end of a 2-h period of status epilepticus, a clear deterioration of the energy state was observed in the cerebral cortex and the hippocampus, but not in the cerebellum. The reduction in adenylate energy charge in the cortex and hippocampus was associated with a seemingly paradoxical decrease in tissue lactate levels and with failure of glycogen resynthesis (cerebral cortex). Experiments with infusion of glucose during the second hour of a 2-h period of status epilepticus verified that the deterioration of tissue energy state was partly due to reduced substrate supply; however, even in animals with adequate tissue glucose concentrations, the energy charge of the two structures was significantly lowered. The cyclic nucleotides (cAMP and cGMP) behaved differently. Thus, whereas cAMP concentrations were either close to control (hippocampus and cerebellum) or moderately increased (cerebral cortex), the cGMP concentrations remained markedly elevated throughout the seizure period, the largest change being observed in the cerebellum. It is concluded that although the localization of neuronal damage and perturbation of cerebral energy state seem to correlate, the results cannot be taken as evidence that cellular energy failure is the cause of the damage. Thus, it appears equally probable that the pathologically enhanced neuronal activity (and metabolic rate) underlies both the cell damage and the perturbed metabolic state. The observed changes in cyclic nucleotides do not appear to bear a causal relationship to the mechanisms of damage.
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PMID:Metabolic changes in cerebral cortex, hippocampus, and cerebellum during sustained bicuculline-induced seizures. 729 97

Carnitine (beta-hydroxy-gamma-trimethylammonium butyrate) is widely distributed in the body including the nervous system. Its physiological function, viz. a carrier of long-chain fatty acids through the inner mitochondrial membrane, has been well established. In this review, mainly based on our experiments, we discuss the possibility that carnitine may have effects other than the "physiological" function and that it may be a potent protector of the brain. When mice were exposed to ammonia (intraperitoneal injection of ammonium acetate), they developed seizures and concentrations of brain energy metabolites were altered; ATP and phosphocreatine decreased while ADP, AMP, pyruvate and lactate increased. The seizures and changes in brain energy metabolites were clearly suppressed when the mice were pre-treated with carnitine. Furthermore, changes in energy metabolites in the brain caused by severe ischemia (decapitation) were also suppressed by carnitine. Since D-carnitine showed similar effects as those of L-carnitine, the effects seem due to function(s) of carnitine yet to be defined. Intrinsic substances including carnitine appear to deserve further studies for possible use in protecting the brain.
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PMID:Protection of the brain by carnitine. 774 96

The N-methyl-D-aspartate (NMDA) receptors are a class of excitatory amino acid receptors in the brain which are important for the induction of kindling and kindling-like phenomena. Post hoc sodium nitroprusside-induced ADP ribosylation of some proteins (particularly a p43 and a p39 protein) in homogenates from stimulated hippocampus was reduced at preconvulsive stage II and stage V (tonic-clonic seizures) of dentate gyrus kindling compared with controls. This effect, which probably reflects enhanced endogenous ADP ribosylation, depends on the progressive activation of the NMDA receptors and on the generation of nitric oxide (NO). The early occurrence and the persistence of these modifications suggest they may be associated to the long-lasting changes in neuronal function induced by kindling.
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PMID:Changes in the ADP-ribosylation status of some hippocampal proteins are linked to kindling progression. 791 68

Somatostatin (SS) and noradrenaline (NA) are distributed in the rat cerebral cortex, and seizure activity is one of the aspects of behavior affected by both neurotransmitters. Due to the possible interaction between both neurotransmitter systems, we studied whether phenylphrine, an alpha 1-adrenoceptor agonist, and prazosin, an alpha 1-adrenoceptor antagonist, can modulate SS-like immunoreactivity (SS-LI) levels, binding of [125I][Tyr11]SS to its specific receptors, the ability of SS to inhibit adenylate cyclase (AC) activity, and the guanine nucleotide binding regulatory protein G, and G., in the Sprague-Dawley rat frontoparietal cortex. An IP dose of 2 or 4 mg/kg of phenylephrine injected 7 h before decapitation decreased the number of SS receptors and increased the apparent affinity in frontoparietal cortex membranes. An IP dose of 20 or 25 mg/kg of prazosin administered 8 h before decapitation increased the number of SS receptors and decreased their apparent affinity. The administration of prazosin before the phenylephrine injection prevented the phenylephrine-induced changes in SS binding. The addition of phenylephrine and/or prazosin 10(-5) M to the incubation medium changed neither the number nor the affinity of the SS receptors in the frontoparietal cortex membranes. Phenylephrine or prazosin affected neither SS-LI content nor the basal or forskolin (FK)-stimulated AC activities in the frontoparietal cortex. In addition, SS caused an equal inhibition of AC activity in frontoparietal cortex membranes of phenylephrine-and prazosintreated rats compared with the respective control group. Finally, phenylephrine and prazosin did not vary the pertussis toxin (PTX)-catalyzed ADP ribosylation of Gi- and/or Go-proteins. These results suggest that the above-mentioned changes are related to the phenylephrine activation of alpha 1-adrenoceptors or to the blocking of these receptors by prazosin. In addition, these data provide further support for a functional interrelationship between the alpha 1-adrenergic and somatostatinergic systems in the rat frontoparietal cortex.
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PMID:Effect of phenylephrine and prazosin on the somatostatinergic system in the rat frontoparietal cortex. 874 58

General pharmacological effects of recombinant human basic fibroblast growth factor (bFGF) were investigated. 1. Central nervous system: Basic FGF produced almost no effect on the general symptoms and behaviors of mice. Basic FGF did not influence the spontaneous motor activity, hexobarbital-induced anesthesia, electroshock seizure threshold, pentylenetetrazole-induced seizure in mice and normal body temperature and spinal reflex in rats up to a dose of 1 mg/kg (s.c., i.v.). As regards pain sensation, it inhibited the acetic acid-induced writhing at 1 mg/kg (s.c.). No abnormal waves were observed in spontaneous EEG of the rabbit up to 1 mg/kg (i.v.) of bFGF, but at 0.1 mg/kg it had a slight effect on the ratio of EEG levels and at 1 mg/kg induced an increase in rest period, disappearance in the period of fast wave sleep and a decrease in the period of deep sleep. 2. Somatic nervous system: Basic FGF did not influence the corneal reflex, twitch response of the skin and diaphragm-phrenic nerve preparations. 3. Autonomic nervous system and smooth muscle: Basic FGF showed little effects on the spontaneous movement of the isolated ileum, contraction induced by various agonists in isolated ileum, resting tension and noradrenaline(NA)-induced contraction of the aorta, resting tension and histamine-induced contraction of isolated trachea, spontaneous movement and 5-HT-induced contraction of isolated strips of stomach fundus, NA-induced contraction of isolated vas deferens of the rat up to the concentration of 10(-4) g/ml. Basic FGF augmented the tone of the isolated non-pregnant uterus at the concentrations of 10(-5) g/ml and above and inhibited or tended to inhibit the contractile tension of non-pregnant or pregnant uterus at 10(-4) g/ml, but it did not influence the spontaneous movement of the uterus, either the non-pregnant or pregnant, under in situ conditions even at a dose of 1 mg/kg (i.v.). Basic FGF did not influence the pupil size. 4. Respiratory and circulatory systems: Basic FGF had no effect on the isolated heart. The influence was not exerted on the heart rate for the isolated atria but slight inhibition of contractile force was observed at 10(-4) g/ml. In anesthetized dogs a decrease in blood pressure, a slight increase in heart rate and respiratory rate and a decrease in femoral blood flow were observed at 0.01 and 0.1 mg/kg (i.v.) of bFGF Similarly, a slight increase in heart rate and a slight decrease of blood pressure were observed at 1 mg/kg (s.c.) in conscious rats. 5. Digestive system: Administration of bFGF at 1 mg/kg did not result in changes in the transport capacity within the gastrointestinal tract (s.c., i.v.) and the secretion of the gastric juice (s.c.). 6. Urine output and electrolyte metabolism: Basic FGF produced a decrease in urinary Na+ excretion at 1 mg/kg (s.c.), and showed a tendency to increase in urinary volume at 0.01 and 0.1 mg/kg (i.v.). At 1 mg/kg (i.v.) urinary excretion of Na+ and Cl- was decreased significantly. It had no effect on the ability of rats to excrete PSP (phenol red) up to 1 mg/kg (s.c.). 7. Blood system: Basic FGF did not influence the coagulation time of the whole blood, prothrombin time and activated partial thromboplastin time of rats up to 1 mg/kg (s.c., i.v.). It did not influence the aggregation of rabbit platelets induced by collagen and ADP up to 10(-4) g/ml. Basic FGF at concentration of 10(-4) g/ml exhibited no hemolytic action. 8. Local action: Plantar subcutaneous injection of bFGF at above 0.005 mg/site induced edema by itself on and after the next day, and also reinforced carrageenin-induced edema from 1 day after injection. The results show that bFGF did not produce any acute effects on the somatic nervous system, autonomic nervous system, smooth muscle and blood system. In contrast, bFGF produced slight effects on the circulatory system, central nervous system and kidney function when injected systemically. Subcutaneous administration may produce edema at the s
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PMID:General pharmacology of recombinant human basic fibroblast growth factor. 884 46

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.
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PMID:In vivo phosphocreatine and ATP in piglet cerebral gray and white matter during seizures. 947 37

Pentachlorophenol (PCP) increased oxygen consumption and lowered the respiratory control ratio (RCR) in mitochondria from rat liver. These effects of PCP were lessened by 1 mM L-carnitine but not by D-carnitine. In contrast, up to 150 mM of pentylenetetrazol (PTZ) added at state 4 of respiration did not accelerate oxygen consumption. When mitochondria were incubated with 3.3 mM of PTZ, oxygen consumption, RCR and ADP/O ratio were all decreased. Moreover, these could not be suppressed even by high concentrations (-20 mM) of L-carnitine. Thus, while L-carnitine could suppress effects of PCP, it could not counteract PTZ in mitochondria. It appears that anticonvulsive effects of carnitine in PTZ-induced seizures may not be due to mitochondrial protection.
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PMID:Effects of pentachlorophenol, pentylenetetrazol and carnitine on mitochondria. 988 82

Impaired energy metabolism may play a critical role in the neuronal injury caused by kainic acid (KA) induced status epilepticus (SE). Following an acute dose of KA (15 mg/kg, s.c.) rats developed SE within 1 h. Rats were sacrificed 1 or 72 h after the onset of SE using a head focused microwave technique and the brain regions (pyriform cortex, amygdala, and hippocampus) were assayed for energy metabolites: ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) using reversed-phase HPLC (RP-HPLC). Control values were significantly higher in cortex (23-32%) than in other brain regions. Within 1 h, SE caused a marked decline in ATP (44-56%), PCr (49-64%), total adenine nucleotides (TAN, 45-50%) and total creatine compounds (TCC, 32-51%). Within three days, the hippocampus showed the greatest recovery, as the reduced values returned to normal. Pretreatment of rats with an antioxidant (PBN, 200 mg/kg, i.p., 30 min prior to KA; or vitamin E (Vit-E), 100 mg/kg, i.p./day for 3 days), which did not prevent seizure activity, attenuated depletion of high-energy phosphates caused by KA. These findings suggest that the depletion of energy metabolites caused by KA-induced seizures may be linked to oxidative stress mediated toxicity.
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PMID:Seizure-induced changes in energy metabolites and effects of N-tert-butyl-alpha-phenylnitrone (PNB) and vitamin E in rats. 1100 54

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 protective effects. Vitamin E has direct antioxidant effects by preventing excessive NO production.
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PMID:Nitric oxide modulates high-energy phosphates in brain regions of rats intoxicated with diisopropylphosphorofluoridate or carbofuran: prevention by N-tert-butyl-alpha-phenylnitrone or vitamin E. 1157 Jun 92


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