Fluctuating and constant valproate administration gives equivalent seizure control in rats with genetic and acquired epilepsy

Dedeurwaerdere, Stefanie; Raay, Leena van; Morris, Margaret J.; Reed, Ronald C.; Hogan, Robert; O’Brien, Terence J.

doi:10.1016/j.seizure.2010.10.011

Cited by 10 publications

(12 citation statements)

References 40 publications

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“…1). This is in line with a previous study from our group showing significant seizure suppression following 3 days of continuous valproate treatment in GAERS [38]. A previous study found that treating non-epileptic Sprague Dawley rats with valproate for four days resulted in a significant increase in NPY expression in the nRT and hippocampus [2].…”

Section: Discussionsupporting

confidence: 93%

“…The seizures in GAERS exhibit a similar pharmacological response to anti-epileptic drugs as for human absence epilepsy, being suppressed by valproate and ethosuximide and aggravated by carbamazepine [36], [37], [38]. For this study GAERS aged between 4–6 months were obtained from the breeding colonies at the Royal Melbourne Hospital and Ludwig Institute for Cancer Research Melbourne, Australia.…”

Section: Methodsmentioning

confidence: 99%

“…Our laboratory has devised an infusion cable that allows for prolonged simultaneous EEG acquisition and intravenous infusion [38], [39]. This involves implantation of a jugular vein cannula (PVC ID = 0.8 mm, OD = 1.2 mm, Microtube Extrusions Pty Ltd, Australia) filled with heparinised saline (20 IU.ml −1 Heparin Sodium DBL, Hameln Pharmaceuticals GmbH, Germany) and tunnelled through the back of the neck to the muscles surrounding the jugular vein.…”

Section: Methodsmentioning

confidence: 99%

“…All rats (n = 17) were given heparinised saline as described above for 3 days and on the 4 th day rats were weighed and assigned randomly to either 42 mg.kg −1 .hr −1 valproate (Sigma, USA) (n = 9) a dose that is known to suppress seizures [38], [40] or saline (n = 8). After 5 days of treatment (day 8) rats were euthanized with an overdose of sodium pentobarbital (1 ml/kg i.p.…”

Section: Methodsmentioning

confidence: 99%

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Long-Term Valproate Treatment Increases Brain Neuropeptide Y Expression and Decreases Seizure Expression in a Genetic Rat Model of Absence Epilepsy

et al. 2013

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The mechanisms by which valproate, one of the most widely prescribed anti-epileptic drugs, suppresses seizures have not been fully elucidated but may involve up-regulation of neuropeptide Y (NPY). We investigated the effects of valproate treatment in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) on brain NPY mRNA expression and seizure control. GAERS were administered either valproate (42 mg.kg−1 hr−1) or saline continuously for 5 days. Electroencephalograms were recorded for 24 hrs on treatment days 1, 3 and 5 and the percentage of time spent in seizure activity was analysed. NPY mRNA expression was measured in different brain regions using qPCR. Valproate treatment suppressed seizures by 80% in GAERS (p<0.05) and increased NPY mRNA expression in the thalamus (p<0.05) compared to saline treatment. These results demonstrate that long-term valproate treatment results in an upregulation of thalamic expression of NPY implicating this as a potential contributor to the mechanism by which valproate suppresses absence seizures.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Long-Term Valproate Treatment Increases Brain Neuropeptide Y Expression and Decreases Seizure Expression in a Genetic Rat Model of Absence Epilepsy

et al. 2013

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“…SE was induced in 13 male Wistar rats (286 ± 4 g) as described before [11,12]. Briefly, by step-wise intraperitoneal (i.p.)…”

Section: Methodsmentioning

confidence: 99%

PET imaging of brain inflammation during early epileptogenesis in a rat model of temporal lobe epilepsy

et al. 2012

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BackgroundRecently, inflammatory cascades have been suggested as a target for epilepsy therapy. Positron emission tomography (PET) imaging offers the unique possibility to evaluate brain inflammation longitudinally in a non-invasive translational manner. This study investigated brain inflammation during early epileptogenesis in the post-kainic acid-induced status epilepticus (KASE) model with post-mortem histology and in vivo with [18F]-PBR111 PET.MethodsStatus epilepticus (SE) was induced (N = 13) by low-dose injections of KA, while controls (N = 9) received saline. Translocator protein (TSPO) expression and microglia activation were assessed with [125I]-CLINDE autoradiography and OX-42 immunohistochemistry, respectively, 7 days post-SE. In a subgroup of rats, [18F]-PBR111 PET imaging with metabolite-corrected input function was performed before post-mortem evaluation. [18F]-PBR111 volume of distribution (Vt) in volume of interests (VOIs) was quantified by means of kinetic modelling and a VOI/metabolite-corrected plasma activity ratio.ResultsAnimals with substantial SE showed huge overexpression of TSPO in vitro in relevant brain regions such as the hippocampus and amygdala (P < 0.001), while animals with mild symptoms displayed a smaller increase in TSPO in amygdala only (P < 0.001). TSPO expression was associated with OX-42 signal but without obvious cell loss. Similar in vivo [18F]-PBR111 increases in Vt and the simplified ratio were found in key regions such as the hippocampus (P < 0.05) and amygdala (P < 0.01).ConclusionBoth post-mortem and in vivo methods substantiate that the brain regions important in seizure generation display significant brain inflammation during epileptogenesis in the KASE model. This work enables future longitudinal investigation of the role of brain inflammation during epileptogenesis and evaluation of anti-inflammatory treatments.

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Photosensitive Epilepsy: Treatment and Prevention: How?

Brancheck¹,

Klein

Hogan

2020

The Importance of Photosensitivity for Epilepsy

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Fluctuating and constant valproate administration gives equivalent seizure control in rats with genetic and acquired epilepsy

Abstract: Administration regimes that result in fluctuating VPA blood levels achieve equivalent sustained seizure suppression as those that maintain steady mid-range concentrations.

Cited by 10 publications

References 40 publications

Long-Term Valproate Treatment Increases Brain Neuropeptide Y Expression and Decreases Seizure Expression in a Genetic Rat Model of Absence Epilepsy

Long-Term Valproate Treatment Increases Brain Neuropeptide Y Expression and Decreases Seizure Expression in a Genetic Rat Model of Absence Epilepsy

PET imaging of brain inflammation during early epileptogenesis in a rat model of temporal lobe epilepsy

Photosensitive Epilepsy: Treatment and Prevention: How?

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