Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metoprine which increases brain histamine by blocking its methylation, was recently demonstrated to inhibit electrically induced tonic convulsions in rats. Its effect was now tested on audiogenic convulsions in genetically audiogenic seizure sensitive rats. Metoprine (20 mg/kg, i.p.) reduced the severity of seizures significantly 4 and 28 h after drug administration. Also the duration of convulsions was significantly decreased. These results agree with an involvement of histaminergic neurons in convulsive phenomena perhaps as a part of an anticonvulsive inhibitory transmitter system.
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PMID:Inhibition of sound-induced convulsions by metoprine in the audiogenic seizure susceptible rat. 303 65

The clinical utility of the carbonic anhydrase (CA) inhibitor acetazolamide (ACTZ) is limited because of rapid development of tolerance to its effects. Tolerance is thought to develop as a result of glial cell proliferation and/or increased CA synthesis. DBA mice, susceptible to audiogenic seizures (AGSs) in an age-dependent manner, have increased CA activity as compared with C57 (non-audiogenic seizure susceptible) mice at 21 and 110 days of age. The present work utilized ACTZ to help determine the relationship between increased CA activity in brain and AGSs in DBA mice. Also, minimal electroshock seizure threshold (EST) was measured at various ages in DBA and C57 mice to determine age-related changes in CNS excitability. EST was significantly lower in DBA as compared with C57 mice at 18 days and between 40 and 115 days of age, suggesting that DBA mice remain hyperexcitable to electrical stimulation after they develop resistance to AGSs. ACTZ ED50s against maximal electroshock seizures (MES) were significantly higher in DBA as compared with C57 mice at 26,36, and 115 days of age. This finding correlates with higher CA activity in this strain at 110 days of age, noted previously. However, at 21 days of age, when CA activity is also higher in DBA versus C57 mice, there were no significant differences in ACTZ ED50s against MES between the strains. ACTZ ED50s against AGSs in DBA mice were considerably lower than ACTZ ED50s against MES in either strain, suggesting that a particular fraction of CA is intimately involved in the production of AGSs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and chronic acetazolamide administration in DBA and C57 mice: effects of age. 308 35

A number of neurochemical and behavioral similarities exist between the genetically epilepsy-prone (GEPR) rat and rats made hypothyroid at birth. These similarities include lower brain monoamine levels, audiogenic seizure susceptibility and lowered electroconvulsive shock seizure threshold. Given these similarities, thyroid hormone status was examined in GEPR rats. Serum samples were collected from GEPR-9 and non-epileptic control rats at 5, 9, 13, 16, 22, 31, 45, 60, 90, 150 and 350 days of age. Serum thyroxine (T4) levels were significantly lower in GEPR-9 rats compared to control until day 22 of age. GEPR-9 thyrotropin (TSH) levels were significantly elevated during the period of diminished serum T4. GEPR-9 triiodothyronine (T3) levels were lower than control throughout the first year of life. The data indicate that the GEPR-9 rat is hypothyroid from at least the second week of life up to 1 year of age. The critical impact of neonatal hypothyroidism on brain function coupled with the development of the audiogenic seizure susceptible trait by the GEPR-9 rat during the third week after birth suggests that neonatal hypothyroidism could be one etiological factor in the development of the seizure-prone state of GEPR-9 rats.
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PMID:Evidence of hypothyroidism in the genetically epilepsy-prone rat. 319 82

Our previous studies have shown an increase in the number of GABAergic and total neurons in the inferior colliculus (IC) of the genetically epilepsy-prone rat (GEPR-9) as compared to the non-seizing Sprague-Dawley (SD) rat. To determine whether an increase in neuron number in the IC is genetically associated with seizure behavior, seizing and non-seizing offspring of GEPR-9 and SD progenitor strains were studied as well as offspring from backcrosses made with F1 and either GEPR-9 or SD rats. In addition, the ontogeny of seizure behavior was studied in seizing rats from these same backgrounds. The development of seizure behavior in GEPR-9s was shown to be dependent on age and the number of exposures to sound stimulus up until the age of 9 weeks. The F1 and F2 generations displayed different audiogenic seizure profiles than those of the two progenitor strains. In the F1 generation, the ratio of seizing to non-seizing rats was always greater than 3:1, and the distribution of seizure scores was similar for males and females. In addition, the off-spring from backcrosses made with F1 rats (high or low seizing) and GEPR-9s displayed maximal audiogenic response scores (ARS) of 9, a characteristic of the GEPR-9s used in this study. The results of these genetic studies indicate a polygenetic inheritance of this autosomal dominant trait of audiogenic seizure susceptibility. For the quantitative study of neuronal density in the IC, neurons were counted from cresyl violet-stained preparations from seizing and non-seizing F1 and F2 rats, backcrosses from different categories and age-matched SD rats. Statistically significant increases in the number of both small (70% increase) and medium-sized (14% increase) neurons occurred in the high seizing animals (ARS = 7-9) as compared to either the non-seizing F2 or SD rats. In addition, a significant increase in the number of small neurons (77% increase) occurred in the high seizing offspring of the F1 X GEPR-9 backcross as compared to that of the non-seizing offspring of the F1 X SD backcross. The data from 25 rats generated a 0.9 coefficient of linear correlation between ARS and the number of small neurons. The results from the anatomical studies suggest that the inheritance of audiogenic seizures appears to be closely linked to the increase in cell number. Therefore, the increase in cell number in the IC may be an important determinant of seizure behavior for GEPR-9s.
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PMID:Anatomical and behavioral analyses of the inheritance of audiogenic seizures in the progeny of genetically epilepsy-prone and Sprague-Dawley rats. 319 4

A light and electron microscopic study of Mg-deficient weanling rats showed structural changes of the lungs associated with the audiogenic seizure-shock episode, and with sudden, spontaneous death or spontaneous recovery after the shock episode. Pathogen-free weanling males were fed a Mg-deficient (Mg-0) or Mg-sufficient (Mg-100) diet and were raised in a gnotobiotic environment. Mg-100 rats (n = 16), unstressed or stressed with noise or strychnine, showed normal lungs. Mg-0 rats (n = 20) experienced audiogenic seizure-shock, followed by hyperventilation with tonic-clonic hyperextension of the back and extremities. The lungs of Mg-0 rats sacrificed during shock showed marked hemorrhage, including petechiae; edema; and atelectasis. Eight that died after a post-shock period of hyperventilation and hyperextension of the spine showed partial recovery of the pulmonary lesion; they showed well-expanded lungs, pleural petechiae, persistent congestion, with mild to moderate pathology. Mg-0 rats killed for study 2 days after the seizure-shock episode showed few small areas of residual lung pathology. Ultrastructural changes after Mg-O shock included aggregated platelets, leukocytes, and occasional reticulocytes in congested capillaries. Surfactant was disrupted during Mg-0 seizure-shock, but a layer closely applied to the surface of the epithelium was evident 2 days after shock. Mg-0 rats dying spontaneously showed nonspecific structural changes of the lung similar to changes reported in the sudden infant death syndrome (SIDS).
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PMID:Structural changes in lungs of magnesium-deficient weanling rats dying spontaneously or after spontaneous recovery from the seizure-shock episode. Possible methods for sudden infant death syndromes. 324 82

Convulsive dose 50s (CD50s) for various convulsive drugs and minimal and maximal electroshock seizure thresholds were determined in DBA and C57 mice. DBA mice had lower maximal electroshock seizure thresholds (MESTs, 15%) and CD50s for homocysteine thiolactone (HTL, 23%) and bicuculline (69%), and a higher CD50 for pentylenetetrazol (PTZ) at 3 weeks of age, the age of maximal audiogenic seizure (AGS) susceptibility. At 8 weeks, when DBA mice are not susceptible to AGSs, significant differences were a lower minimal electroshock seizure threshold (mEST, 37%) and maximal EST (MEST) (19%), lower CD50s for N-methyl-D-aspartate (NMDA) (39%), kainic acid (KA, 50%), HTL (32%), strychnine (37%), and a higher CD50 for nicotine (55%) in DBA mice. Based on these data it is suggested that pathways involving NMDA and KA receptors are responsible for increased susceptibility to seizure initiation (mEST), and are opposed by glycine pathways, and that opposing GABA and cholinergic systems at higher CNS levels are involved in seizure spread (AGSs and MEST) in these mice. Latency patterns indicate that nicotine, strychnine, PTZ and bicuculline have high blood-brain barrier (BBB) penetrability. Picrotoxin and the excitatory amino acid receptor agonists had longer latencies, suggesting low BBB penetrability. Age-related changes in latency, however, give evidence that difficulty in drug penetration of the BBB is not responsible for differences observed in CD50s between strains.
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PMID:Seizure susceptibility in DBA and C57 mice: the effects of various convulsants. 329 31

The incidence and severity of audiogenic seizures in kanamycin (KM)-treated rat pups, from a Wistar strain which is inherently seizure-resistant, was analyzed as a function of (a) postnatal age at the time of KM injection (i.p.) and (b) KM dosage. The vigor of the pinna reflex response on postnatal day (PND) 28 was correlated with (a) age at the time of injection, (b) dosage and (c) individual audiogenic seizure severity scores on PND 28 or PND 32. The data indicate that PNDs 9-12 are the developmental period when the rat has its greatest sensitivity to induction of susceptibility to audiogenic seizures by KM. The pinna reflex data suggest that cochlear vulnerability to KM intoxication is also greatest during this period. The optimum dosage for the induction of susceptibility was 100 mg/kg X 4 days. Use of higher doses resulted in a reduction of both incidence and severity of audiogenic seizures. The pinna reflex generally exhibited a supranormal vigor in animals having the most severe seizures. The behavioral attributes of induced audiogenic seizures at postnatal ages of 28 and 32 days are described and discussed.
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PMID:The sensitive period and optimum dosage for induction of audiogenic seizure susceptibility by kanamycin in the Wistar rat. 335 Jul 70

Local cerebral glucose consumption (l-CMRgl) was studied using [14C]2-deoxyglucose autoradiography in minimally restrained rats during acute (12 or 18 h postwithdrawal (p.w.] and late (14 days p.w.) ethanol withdrawal, as well after 10 previous, weekly withdrawal episodes as after a similar period of isocalorical feeding. A period of two days of intoxication was established by gastric intubation. Spontaneous incomplete convulsive seizures were observed during the 8th to 10th withdrawal episode. Audiogenic seizures occurred following stimulation during the 6th and 10th withdrawal episode. Animals with previous spontaneous or audiogenic seizure were distributed randomly and evenly among the groups. l-CMRgl values were adjusted to a temperature of 38 degrees C. During acute withdrawal, l-CMRgl was significantly reduced by 18-32% in cortical and most limbic regions, but unchanged in cerebellum and subcortical structures as compared with the neutral state (late withdrawal and control groups). l-CMRgl was relatively more lowered in the amygdala in animals with previous spontaneous withdrawal seizures and in structures belonging to the auditory system in animals with previous audiogenic seizures. l-CMRgl did not differ among neutral groups. The lowered l-CMRgl in cortical and limbic regions during withdrawal contrasts to the results of previous studies. This difference may be attributed to the minimal restraint of animals in this study. The pattern of l-CMRgl in acute and late withdrawal animals with previous spontaneous withdrawal seizures is consistent with a mechanism comparable to electrical amygdala kindling contributing to seizure genesis.
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PMID:Local cerebral glucose consumption during ethanol withdrawal in the rat: effects of single and multiple episodes and previous convulsive seizures. 340 59

DBA/2J mice exhibit audiogenic seizure susceptibility (AGSS) and lower electroshock seizure thresholds compared with C57BL/6J mice. Thyroid function, including thyroxine (T4), 3,5,3'-triiodothyronine (T3), and thyrotropin (TSH) concentrations, T4/T3 ratio, and iodide uptake, of DBA and C57 mice were compared. Thyroid function was also assessed in relation to AGSS and severity in DBA mice. DBA mice have a larger thyroidal pool of iodide due to increased iodide uptake and possibly decreased release, but not to an increased organification rate. This increased iodide uptake exists until about 40 days of age. DBA mice also have a decreased radiochloride space and increased thyroid weight, indicative of enhanced TSH activity. The DBA mice show high T4 and TSH concentrations and a high T4/T3 ratio between the ages of 20 and 40 days. Beginning at 40 days of age the DBA mice have high T4, TSH, and T3 concentrations leading to a T4/T3 ratio approximating the C57 ratio. At any age, DBA mice demonstrating clonic/tonic seizures in response to auditory stimulation have hormone concentrations similar to their 21-day-old counterparts with seizures. Mice that show decreased response to auditory stimulation have hormone concentrations similar to the older age group. The increased thyroid activity of DBA mice is the result of enhanced TSH secretion. The increased TSH production is due to adaptations corresponding to the different age and AGSS. A decreased conversion of T4 to T3 by 3,3,5'-monodeiodinase, is responsible for the increase in TSH due to loss of T3 negative feedback on the anterior pituitary gland. By 40 days of age, the Type I 5'-deiodinase matures whereas the brain deiodinase activity remains subnormal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparison of thyroid function in DBA/2J and C57BL/6J mice. 340 39

Abnormalities in noradrenaline-mediated neurotransmission have been advocated as a basis of the age-related susceptibility of DBA/2J mice to generalised convulsions induced by auditory stimulation. We have measured the kinetics of synaptosomal high-affinity noradrenaline uptake in 5 brain regions of DBA/2J mice at ages before, during and after their maximal susceptibility to audiogenic seizures, and age-matched C57 BL/6 mice, a strain resistant to audiogenic seizures at all ages. No differences were found between the two strains of mice in any of the brain regions studied. Abnormalities of high-affinity noradrenaline uptake do not contribute to audiogenic seizure susceptibility of DBA/2J mice.
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PMID:Synaptosomal high-affinity noradrenaline uptake does not differ between mice susceptible (DBA/2J) and resistant (C57 BL/6) to audiogenic seizures. 350 89


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