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Seizure Induction (seizure + induction)
Selected AbstractsfMRI of Generalized Absence Status Epilepticus in Conscious Marmoset Monkeys Reveals Corticothalamic ActivationEPILEPSIA, Issue 10 2004Jeffrey R. Tenney Summary:,Purpose: A nonhuman primate model of generalized absence status epilepticus was developed for use in functional magnetic resonance imaging (fMRI) experiments to elucidate the brain mechanisms underlying this disorder. Methods: Adult male marmoset monkeys (Callithrix jacchus) were treated with ,-butyrolactone (GBL) to induce prolonged absence seizures, and the resulting spike,wave discharges (SWDs) were analyzed to determine the similarity to the 3-Hz SWDs that characterize the disorder. In addition, blood-oxygenation-level,dependent (BOLD) fMRI was measured at 4.7 Tesla after absence seizure induction with GBL. Results: Electroencephalographic recordings during imaging showed 3-Hz SWDs typical of human absence seizures. This synchronized EEG pattern started within 15 to 20 min of drug administration and persisted for >60 min. In addition, pretreatment with the antiepileptic drug, ethosuximide (ESM), blocked the behavioral and EEG changes caused by GBL. Changes in BOLD signal intensity in the thalamus and sensorimotor cortex correlated with the onset of 3-Hz SWDs. The change in BOLD signal intensity was bilateral but heterogeneous, affecting some brain areas more than others. No significant negative BOLD changes were seen. Conclusions: The BOLD fMRI data obtained in this marmoset monkey model of absence status epilepticus shows activation within the thalamus and cortex. [source] Corticothalamic Modulation during Absence Seizures in Rats: A Functional MRI AssessmentEPILEPSIA, Issue 9 2003Jeffrey R. Tenney Summary:,Purpose: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. Methods: Blood-oxygenation-level,dependent (BOLD) fMRI in the brain was measured by using T2*-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using ,-butyrolactone (GBL; 200 mg/kg, intraperitoneal). Results: The corticothalamic circuitry, critical for spike,wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. Conclusions: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents. [source] Dynamic Variations of Local Cerebral Blood Flow in Maximal Electroshock Seizures in the RatEPILEPSIA, Issue 10 2002Véronique André Summary: ,Purpose: Measurement of cerebral blood flow is routinely used to locate the areas involved in generation and spread of seizures in epilepsy patients. Because the nature of the hyperperfused regions varies with the timing of injection of tracer, in this study, we used a rat model of maximal electroshock seizures to follow up the time-dependent changes in the distribution of seizure-induced cerebral blood flow (CBF) changes. Methods: CBF was measured by the quantitative autoradiographic [14C]iodoantipyrine technique over a 30-s duration. The tracer was injected either at 15 s before seizure induction, simultaneous with the application of the electroshock (tonic phase), at the onset of the clonic phase, or at 3 and 6 min after the seizure (postictal phase). Results: Rates of CBF underwent dynamic changes during the different phases of seizure activity and largely increased over control levels (,400%) in the 45 regions studied during all phases of the seizure (first 3 times). CBF remained higher than control levels in 35 and 15 areas at 3 and 6 min after the seizure, respectively. Conclusions: The distribution of maximal CBF increases showed a good correlation with their known involvement in the circuits underlying the clinical expression of the different types of seizure activity, tonic versus clonic. [source] Spectral analysis of electrocorticographic activity during pharmacological preconditioning and seizure induction by intrahippocampal domoic acidHIPPOCAMPUS, Issue 8 2010P.M. Sawant Abstract Previously we have shown that low-dose domoic acid (DA) preconditioning produces tolerance to the behavioral effects of high-dose DA. In this study, we used electrocorticography (ECoG) to monitor subtle CNS changes during and after preconditioning. Young adult male Sprague-Dawley rats were implanted with a left cortical electrode, and acute recordings were obtained during preconditioning by contralateral intrahippocampal administration of either low-dose DA (15 pmoles) or saline, followed by a high-dose DA (100 pmoles) challenge. ECoG data were analyzed by fast Fourier transformation to obtain the percentage of baseline power spectral density (PSD) for delta to gamma frequencies (range: 1.25,100 Hz). Consistent with previous results, behavioral analysis confirmed that low-dose DA preconditioning 60 min before a high-dose DA challenge produced significant reductions in cumulative seizure scores and high level seizure behaviors. ECoG analysis revealed significant reductions in power spectral density across all frequency bands, and high-frequency/high-amplitude spiking in DA preconditioned animals, relative to saline controls. Significant correlations between seizure scores and ECoG power confirmed that behavioral analysis is a reliable marker for seizure analysis. The reduction ofpower in delta to gamma frequency bands in contralateral cortex does not allow a clear distinction between seizure initiation and seizure propagation, but does provide objective confirmation that pharmacological preconditioning by DA reduces network seizure activity. © 2009 Wiley-Liss, Inc. [source] The Salt-Inducible Kinase, SIK, Is Induced by Depolarization in BrainJOURNAL OF NEUROCHEMISTRY, Issue 6 2000Jonathan D. Feldman Abstract: Membrane depolarization of neurons is thought to lead to changes in gene expression that modulate neuronal plasticity. We used representational difference analysis to identify a group of cDNAs that are induced by membrane depolarization or by forskolin, but not by neurotrophins or growth factors, in PC12 pheochromocytoma cells. One of these genes, SIK (salt- inducible kinase), is a member of the sucrose-nonfermenting 1 protein kinase/AMP-activated protein kinase protein kinase family that was also recently identified from the adrenal gland of rats treated with high-salt diets. SIK mRNA is induced up to eightfold in specific regions of the hippocampus and cortex in rats, following systemic kainic acid administration and seizure induction. [source] Characterization of the anticonvulsant profile and enantioselective pharmacokinetics of the chiral valproylamide propylisopropyl acetamide in rodentsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003Nina Isoherranen Propylisopropyl acetamide (PID) is a new chiral amide derivative of valproic acid. The purpose of this study was to evaluate the anticonvulsant activity of PID in rodent models of partial, secondarily generalized and sound-induced generalized seizures which focus on different methods of seizure induction, both acute stimuli, and following short-term plastic changes as a result of kindling, and to assess enantioselectivity and enantiomer,enantiomer interactions in the pharmacokinetics and pharmacodynamics of racemic PID and its pure enantiomers in rodents. Anticonvulsant activity of (S)-PID, (R)-PID and racemic PID was evaluated in the 6 Hz psychomotor seizure model in mice, in the hippocampal kindled rat, and in the Frings audiogenic seizure susceptible mouse. The pharmacokinetics of (S)-PID and (R)-PID was studied in mice and rats. In mice (S)-PID, (R)-PID and racemic PID were effective in preventing the 6 Hz seizures with (R)-PID being significantly (P<0.05) more potent (ED50 values 11 mg kg,1, 46 mg kg,1 and 57 mg kg,1 at stimulation intensities of 22, 32 and 44 mA, respectively) than (S)-PID (ED50 values 20 mg kg,1, 73 mg kg,1 and 81 mg kg,1 at stimulation intensities of 22, 32 and 44 mA, respectively). (S)-PID, (R)-PID and racemic PID also blocked generalized seizures in the Frings mice (ED50 values 16 mg kg,1, 20 mg kg,1 and 19 mg kg,1 respectively). In the hippocampal kindled rat a dose of 40 mg kg,1 of (R)- and (S)-PID prevented the secondarily generalized seizure, whereas racemic PID also blocked the expression of partial seizures following an i.p. dose of 40 mg kg,1. Racemic PID also significantly increased the seizure threshold in this model. Mechanistic studies showed that PID did not affect voltage-sensitive sodium channels or kainate-, GABA- or NMDA- evoked currents. The pharmacokinetics of PID was enantioselective following i.p. administration of individual enantiomers to mice, with (R)-PID having lower clearance and longer half-life than (S)-PID. In rats and mice, no enantioselectivity in the pharmacokinetics of PID was observed following administration of the racemate, which may be due to enantiomer,enantiomer interaction. This study demonstrated that PID has both enantioselective pharmacokinetics and pharmacodynamics. The better anticonvulsant potency of (R)-PID in comparison to (S)-PID may be due to its more favorable pharmacokinetic profile. The enhanced efficacy of the racemate over the individual enantiomers in the kindled rat may be explained by a pharmacokinetic enantiomer,enantiomer interaction in rats. This study also showed the importance of studying the pharmacokinetics and pharmacodynamics of chiral drugs following administration of the individual enantiomers as well as the racemic mixture. British Journal of Pharmacology (2003) 138, 602,613. doi:10.1038/sj.bjp.0705076 [source] | |||||||||||||