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

In this chapter, we review the major inherited convulsive disorders found in mice and discuss their possible relationship to specific clinical seizure disorders in humans. These disorders in mice include audiogenic seizures, the epilepsy (El) mouse, various spontaneous seizures, the tottering/leaner syndrome, seizures associated with cerebellar abnormalities, seizures associated with myelin disorders, and alcohol withdrawal seizures. We find that for most major types of epilepsy in humans, there exists a similar counterpart in the mouse. Because human and rodent nervous systems respond similarly to seizure-provoking stimuli, it is possible that biochemical and physiological mechanisms of naturally occurring convulsive disorders are also similar in these species. The use of recombinant inbred (RI) and congenic mouse strains for genetic and biochemical studies of audiogenic seizures is presented. Using these strains, we have identified a major gene, Ias, that inhibits the spread of seizure activity. This gene was found through its close linkage with the Ah locus on chromosome 17. We also found that juvenile-onset and adult-onset audiogenic seizures are controlled by different genetic systems. The problem of juvenile-onset audiogenic seizure susceptibility is especially interesting because these seizures are genetically associated with an ecto-Ca2+-ATPase deficiency among the RI strains. This deficiency is the first neurochemical trait found to be inherited together with an idiopathic convulsive disorder, and may represent a potentially important basic mechanism of epilepsy. Because the brains of human epileptics are generally inaccessible for neurochemical research, the epileptic mouse mutants offer a convenient means of pursuing this type of research. The well-known genetic constitution of the mouse, together with the availability of numerous physiologically distinct convulsive disorders, makes the mouse ideally suited for molecular, genetic, and biochemical studies of convulsive behavior.
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PMID:Inherited convulsive disorders in mice. 351 45

The postnatal development of susceptibility to the convulsant effects of Ro5-4864 (4'-chlorodiazepam) was characterized in two inbred mouse strains (DBA/2J and BALB/c ByJ) which as adults differ markedly in their response to this convulsant. Onset of susceptibility to a dose of Ro5-4864 which caused a high frequency of clonic seizures in adults was observed at 10 days of age in DBA/2 mice, but not until 35 days in BALB/c By mice. At 14 days of age an abrupt increase in susceptibility to Ro5-4864-induced tonic seizures was found in DBA/2 but not BALB/c By mice. Both the peak of tonic seizure susceptibility (21 days) and the time course of its subsequent age-dependent decline closely paralleled the change in audiogenic seizure susceptibility in the DBA/2 strain. PK11195 (40 mg/kg) blocked Ro5-4864 (25 mg/kg)-induced, age-dependent tonic seizures but had no effect on clonic seizure induction in the same mice. These observations establish that both the susceptibility to Ro5-4864 in adult mice and the postnatal time course for development of susceptibility to this convulsant are inherently different in these two strains of mice. The lack of coincidence between the developmental onset of susceptibility to Ro5-4864-induced seizures and the onset of supersensitivity to Ro5-4864-induced tonic seizures during the period of peak audiogenic seizure susceptibility in DBA/2 mice implies that more than one neurochemical mechanism is involved in the ability of Ro5-4864 to induce seizures in this strain. However, the blockade of Ro5-4864-induced tonic seizures by PK11195 suggests that peripheral type benzodiazepine receptors may mediate this effect.
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PMID:Ontogeny of susceptibility to the convulsant, Ro 5-4864, and its relationship to audiogenic seizure susceptibility in inbred mice. 356 Nov 51

The levels of 12 guanidino compounds were determined in serum and brain of audiogenically sensitive rats with and without seizures. During audiogenic seizures the serum levels of creatine are significantly decreased, while those of guanidinoacetic acid, N-alpha-acetylarginine, creatinine, gamma-guanidinobutyric acid, arginine, guanidine and methylguanidine are significantly increased. In brain only creatinine and N-alpha-acetylarginine are markedly increased during seizure. These data demonstrate noticeable modifications of the levels of guanidino compounds in the blood during audiogenic seizure and also, in parallel, a creatinine increase in serum and brain.
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PMID:Guanidino compounds in serum and brain of audiogenically sensitive rats. 356 23

The EEG of 20 Wistar rats inbred for audiogenic seizures was recorded during 40 daily auditory stimuli 90 s long. The first stimuli provoked wild running, with no cortical EEG abnormality, and then a tonic phase with a characteristic EEG of a brief flat trace 2 to 3 s long followed by low-amplitude regular activity, 10 to 12 c/s, lasting 40 to 60 s. The lack of paroxysmal EEG patterns suggests that the cortex plays only a minor role in audiogenic seizure development. After 5 to 15 daily stimuli, the EEG during the running period exhibited brief spike and spike-wave discharges preceding the EEG pattern of the tonic phase. After a few more daily stimuli these paroxysmal discharges progressively increased in amplitude and duration, overlapping with the regular activity of the tonic phase. After 20 to 30 stimuli, only high-amplitude spikes and spike-waves, 1 to 10 c/s, were seen for 40 to 120 s. The modified EEG persisted 2 to 4 months after daily stimulation was discontinued. Thus, with stimulus repetition, a paroxysmal discharge progressively involved cortical structures. These data suggest that repetition of audiogenic seizures induced a phenomenon related to kindling in Wistar rats susceptible to sound-induced epilepsy.
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PMID:Kindling of audiogenic seizures in Wistar rats: an EEG study. 358 60

A light- and electron-microscopic study was made of the lungs of magnesium (Mg)-sufficient and Mg-deficient pathogen-free weanling rats raised in a gnotobiotic environment. Mg-sufficient rats were studied unstressed, after mild auditory stress, or after strychnine seizures and showed essentially no pulmonary pathology. Mg-deficient rats were studied with no known seizures or immediately after audiogenic seizure-shock. Light microscopy of lung from Mg-deficient rats with audiogenic seizure-shock revealed atelectasis, generalized edema and hemorrhage, and pleural petechiae. Ultrastructural changes in lung alveoli of Mg-deficient rats with seizure-shock included gaps in capillary endothelium, swelling and separation of endothelial cells from the underlying basement membranes; Type I cell necrosis and separation from basement membranes; and intraalveolar red blood cells, fibrin, and precipitated plasma. The seizure-shock episode of acute Mg deficiency produces structural changes in the lung similar to changes produced by several forms of shock, early acute oxygen toxicity, and the respiratory distress syndrome (RDS) in human neonates.
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PMID:Pulmonary lesion induced by stress in magnesium-deficient rats. A light- and electron-microscopic study. 359 2

In the early 1950s, Frings and Frings began a process of selection for audiogenic seizure susceptibility and resistance in albino mice. The present study was conducted to examine behavioral and cochlear functions in the inbred descendants of these mice. The cochlear action potential (AP) thresholds of the susceptible RB/1bg inbred mice were abnormally high, and the resistant inbred RB/3bg mice had normal AP audiograms. The F1 hybrid showed heterosis for its cochlear function. Only the RB/1bg was susceptible to audiogenic seizures on the first acoustic exposure. Thresholds for the successive components of their audiogenic seizures were determined in response to narrow bands of noise. These paralleled the AP thresholds of RB/1bg mice (r = .89). This RB/1bg mouse showed little age-related cochlear loss, which probably accounts for its robust sensitivity to audiogenic seizures over most of its lifespan. Earlier studies had demonstrated that the susceptible RB line had a robust AP, but little or no cochlear microphonic (CM). The susceptible RB/1bg had well-defined AP and CM responses at low frequencies. The nonsusceptible RB/3bg mice were more resistant to acoustic priming than another mouse (CBA/J) strain with a similar audiometric profile.
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PMID:Auditory physiology and behavior in RB/1bg, RB/3bg, and their F1 hybrid mice (Mus musculus): influence of genetics, age, and acoustic variables on audiogenic seizure thresholds and cochlear functions. 369 82

The genetically epilepsy-prone rat (GEPR) is abnormally susceptible to induction of seizures by acoustic stimulation. The inferior colliculus (IC) is critically important to audiogenic seizure susceptibility. The GEPR is more susceptible to induction of audiogenic seizures at 12 kHz than at other pure tone frequencies. IC neurons in the GEPR exhibit significantly elevated response thresholds and broader tuning characteristics than normal. These findings along with previous neurophysiological and anatomical data suggest that a hearing deficit occurs in the GEPR. IC neurons in the GEPR exhibit a significantly elevated incidence of a response pattern with a peak of activity at the beginning and end of the stimulus, the onset-offset response. This response pattern occurs at 12 kHz and at characteristic frequency with high stimulus intensities and may represent an afterdischarge phenomenon. The onset-offset pattern may be a manifestation of central mechanisms developed to compensate for reduced peripheral auditory input that appears to be involved in the hearing deficit of the GEPR. Such compensatory mechanisms may involve alterations of the actions of neurotransmitters of the brain-stem auditory nuclei. GABA is implicated as an inhibitory transmitter in the IC. Iontophoretic application of GABA or a benzodiazepine produces significantly less inhibition of IC neurons of the GEPR than of the normal rat. Endogenous sound-induced (binaural) inhibition which is suggested to be GABA-mediated is also significantly reduced in IC neurons of the GEPR. Iontophoresis of the GABAA antagonist, bicuculline, often converts normal response patterns in the IC to onset-offset responses seen with high incidence in GEPR IC neurons, suggesting that the decreased effectiveness of GABA may lead to the onset-offset prevalence. This reduced effectiveness of inhibition may be unable to compensate for the rise in the putative excitatory transmitter, aspartate, in IC during high intensity acoustic stimulation in the GEPR. These altered transmitter actions may be important mechanisms subserving initiation of audiogenic seizures in the genetically epilepsy-prone rat.
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PMID:Inferior colliculus neuronal response abnormalities in genetically epilepsy-prone rats: evidence for a deficit of inhibition. 374 11

Pharmacological studies demonstrate a reciprocal relationship between both noradrenergic and serotonergic transmission and audiogenic seizure severity and susceptibility in the genetically epilepsy-prone rat (GEPR). In contrast, drug-induced changes in the neurochemical indices of dopaminergic activity do not result in alterations in seizure severity. These pharmacological investigations led to the hypothesis that both noradrenergic and serotonergic neurons are capable of regulating seizure severity in the GEPR. Pharmacological investigations also provided evidence that monoaminergic neurons serve as determinants of seizure susceptibility in these epileptic animals. The GEPR is susceptible to environmentally-induced seizures which cannot be precipitated in neurologically normal subjects. Drug studies suggest that monoaminergic decrements serve as one set of susceptibility determinants. However, non-monoaminergic abnormalities also play important roles in the seizure predisposition which characterizes the GEPR. Pathophysiological studies have confirmed and extended the concepts generated by the pharmacological investigations. Noradrenergic and serotonergic deficits do indeed characterize the seizure naive state of the GEPR. These studies have provided a basis for tentative identification of areas of the brain in which monoaminergic abnormalities regulate seizure severity and susceptibility. Monoaminergic defects in some areas such as the thalamus may regulate both susceptibility and severity. In other areas, defects may regulate only severity or susceptibility. In the striatum, noradrenergic defects do not appear to be present and probably are not determinants of the epileptic state of the GEPR.
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PMID:Noradrenergic and serotonergic determinants of seizure susceptibility and severity in genetically epilepsy-prone rats. 374 29

DBA/2J (DBA) mice are susceptible to audiogenic seizures (AGSs) in an age-dependent manner, susceptibility being maximal at 21 days and absent at 110 days of age. Previous studies have demonstrated that there is a decrease in anion transport and an increase in carbonic anhydrase (CA) activity in brain from DBA mice as compared with C57BL/6J (C57, non-AGS) mice at 21 days. Since these results suggest that there are alterations in cellular and electrolyte composition of brain from DBA mice, the present work was directed toward determining electrolyte content, extracellular space, and DNA content of brain from DBA and C57 mice at 21 and 110 days of age. There was a decrease in intracellular chloride and sodium content, and an increase in intracellular potassium content in cerebral cortex, cerebellum, and brainstem from DBA mice at both 21 and 110 days. Also, extracellular space was larger in these three brain tissues from DBA mice at both ages. DNA content, not different between the strains at 21 days, was significantly lower in cerebellum from DBA mice at 110 days. These findings give further evidence of alterations in the transport of ions in brain from DBA mice. In addition, they demonstrate that there are alterations in the intracellular and extracellular space values, an indication of changes in cellular composition of brain in these mice. Such changes may contribute to AGS susceptibility by disrupting the balance that normally exists in the neuronal microenvironment of the central nervous system.
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PMID:Extracellular (36Cl) space, electrolyte, protein, and DNA content in brain of DBA and C57 mice: effects of age. 395 50

The rise and fall of audiogenic seizure vulnerability were followed in three lines of mice selected for brain/body weight ratio and in the heterogeneous stock from which they were derived. Over a period of 12 to 24 days, susceptibility increased and then declined. Subjects retested after a 2-day interval were more susceptible, but this priming effect declined steadily. Differences in seizure threshold varied unsystematically among the lines. No sex differences in susceptibility were found. Mice who seized were heavier on the average than nonseizers of the same age and line. It is proposed that mice with a slower development rate are less susceptible to the stimulus used to evoke seizures. If so, rapid development may tend to lower the threshold of audiogenic seizures in mice.
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PMID:Effects of maturation and priming on audiogenic seizure thresholds in mice. 397 63


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