A minimum of 3 months of dietary fish oil supplementation is required to raise amygdaloid afterdischarge seizure thresholds in rats - implications for treating complex partial seizures

Taha, Ameer Y.; Trépanier, Marc-Olivier; Ciobanu, F; Taha, Nadeen M. Y.; Ahmed, Muaz O.; Zeng, Qiudi H.; Cheuk, Waiyin I.; Ip, Bryan; Filo, Elvis; Scott, Bradley; Burnham, W.M.; Bazinet, Richard P.

doi:10.1016/j.yebeh.2012.12.004

Cited by 25 publications

(16 citation statements)

References 61 publications

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“…Previous studies have demonstrated protective activity of DHA in PTZ as well as kindling models of epilepsy (Taha et al 2010b(Taha et al , 2013aMusto et al 2011;Trépanier et al 2012Trépanier et al , 2014. Our study is the first report indicating that DHA augments the anticonvulsant activity of standard AEDs valproate and lamotrigine in animal models of seizure and epilepsy.…”

Section: Probit Of Responsesupporting

confidence: 63%

“…Numerous in vitro, in vivo, and clinical studies have evaluated possible anticonvulsant activity of DHA, with positive or negative results. According to the nonclinical studies, anticonvulsant potency of DHA is much lower than that of the current standard AEDs (Voskuyl et al 1998;Willis et al 2009;Taha et al 2010aTaha et al , b, 2013aMusto et al 2011;Trépanier et al 2012). Short-term clinical trials that used n-3 PUFAs as a supplement to AEDs in treatment of refractory epilepsies have neither come up with promising results (Yuen et al 2005;Bromfield et al 2008;Taha et al 2010a).…”

Section: Introductionmentioning

confidence: 99%

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Synergistic effect of docosahexaenoic acid on anticonvulsant activity of valproic acid and lamotrigine in animal seizure models

Gavzan

Sayyah

Sardari

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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Add-on therapy is a common strategy to improve efficacy and tolerability of antiepileptic drugs (AEDs). Anticonvulsant potential and appropriate safety of docosahexaenoic acid (DHA) makes it a promising candidate for combination therapy. We evaluated influence of DHA on anticonvulsant activity of AEDs phenytoin, valproate, and lamotrigine in maximal electroshock (MES), pentylenetetrazole (PTZ), and kindling models of epilepsy. The dose-response to DHA was obtained 15 min after intracerebroventricular (i.c.v.) injection in PTZ model of clonic seizures in mice, MES model of tonic seizures in mice, and kindling model of complex partial seizures in rats. The dose-response curve of valproate (30 min after i.p. injection to mice) in PTZ, phenytoin (60 min after i.p. injection to mice) in MES, and lamotrigine (60 min after i.p. injection to rats) in kindling models were obtained. Dose-response curves of the AEDs were then achieved in the presence of ED25 of DHA. DHA had no anticonvulsant effect in the MES model. However, it showed a dose-dependent protective effect against PTZ (ED50 = 0.13 μM) and kindled seizures (ED50 = 1.08 mM). DHA at ED25 caused a 3.6-fold increase in potency of valproate as its ED50 value from 117.5 (98.3-135.3) decreased to 32.5 (21.6-44.1) mg/kg. Moreover, a 4.9-fold increase in potency of lamotrigine occurred, as its ED50 value from 13.10 (11.50-14.9) decreased to 2.65 (0.8-5.6) mg/kg. CompuSyn analysis indicated synergistic anticonvulsant interaction between DHA and both valproate and lamotrigine. Co-administration strategy of the safe and inexpensive anticonvulsant compound DHA with AEDs should be favorably regarded in clinical studies of epilepsy treatment.

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Section: Probit Of Responsesupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Synergistic effect of docosahexaenoic acid on anticonvulsant activity of valproic acid and lamotrigine in animal seizure models

Gavzan

Sayyah

Sardari

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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“…After PTZ administration, epileptiform activity was observed in the three groups of treated animals and no significant differences between groups were observed. These results are not in accordance with previous studies in which an increase in the after discharge threshold in amygdala of rats treated with chronic administration of fish oil was observed (Gilby, JAns, & McIntyre, ; Taha and others ). Discrepancies between previous studies and our work could be due to the time period of treatments, routes of administration and dosages used, or even the seizure models used.…”

Section: Resultscontrasting

confidence: 99%

Effect of Chronic Krill Oil Supplement on Seizures Induced by Pentylenetetrazole in the Hippocampus of Adult Rats with Previous Febrile Seizures

Medina‐Ceja

Villalpando‐Vargas

Cruz

et al. 2019

Journal of Food Science

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We evaluated the effect of krill oil (KO) supplement on seizures induced by pentylenetetrazole (PTZ) in animals with previous febrile seizures (FSs) induced by hyperthermia to determine its effectiveness in seizure susceptibility and as an anticonvulsant. Male Wistar rats with FS separated into water (W, 1 mL), palm oil (PO, 300 mg/kg, total volume 1 mL), or KO (300 mg/kg, total volume 1 mL) groups. All drugs were administered chronically via the intragastric route. Electrical activity was recorded by intracranial EEG simultaneously with convulsive behavior. All animals’ brains were processed by immunofluorescence against GFAP, NeuN, and connexins (Cx); cellular quantification was performed in hippocampus and pyramidal or granular layer thickness was evaluated with cresyl violet (CV) staining. The results showed a significant delay in convulsive behavior and a slight increased survival time after PTZ administration in the group treated with KO compared with PO and W groups. The epileptiform activity showed high amplitude and frequency, with no significant differences between groups, nor were there differences in the number and duration of discharge trains. KO and PO increased the number of astrocytes and the number of neurons compared with the W group. KO and PO decreased the expression of Cx36 without affecting Cx43 expression or the thickness of layers. Based on these data, we consider it important to perform more experiments to determine the anticonvulsant role of KO, taking into account the partial effect found in this study. KO could be used as a coadjuvant of traditional anticonvulsive treatments. Practical Application In this study was evaluated the anticonvulsive effect of a chronic krill oil (KO) supplement in animals with seizures. Results showed that KO had partial anticonvulsive effects measured by EEG activity and convulsive behavior analysis. These data justify further research that looks at KO supplementation as a prospective coadjuvant of pharmacologic management of seizure disorder.

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“…The observed positive therapeutic effect of DHA and EPA on patients with DRE is consistent with animal models treated with EPA and DHA for long duration [16][17][18][19][20] . Interestingly, a timecourse study conducted by Taha et al showed that at least 3 months are required for DHA and EPA to raise seizure threshold 36 . The delayed effect of DHA and EPA was attributed to the slow process of enriching the neuronal tissues with these fatty acids, delay in formation of unestrified EPA and DHA or their bioactive metabolite such as protectins (NPD1) 20 .…”

Section: Discussionmentioning

confidence: 99%

The differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on seizure frequency in patients with drug-resistant epilepsy — A randomized, double-blind, placebo-controlled trial

Ibrahim

Ghebremeskel

Abdel-Rahman

et al. 2018

Epilepsy & Behavior

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Objectives: The omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to play an important role in maintenance and modulation of neuronal functions. There is evidence that omega-3 fatty acids may have anticonvulsant effects. The effect of DHA and EPA on seizure rate in patients with DRE was investigated. Methods: A double-blind, randomized, placebo-controlled clinical trial included ninety-nine (n=99) DRE subjects, aged 5-16 (n=85) and 17-45 (n=14). After randomization, subjects were given two, four or six capsules per day of DHA (417.8 mg DHA and 50.8 mg EPA/capsule, n=33), EPA (385.6 mg EPA and 81.2 mg DHA/capsule, n=33) or placebo (high oleic acid sunflower oil, n=33) for one year. The primary endpoint was the effect of treatment on rate of seizure. Random-effects negative binomial regression models were fitted to model the patients' total count of seizures per month. The treatment effects on seizure incidence rate ratio was tested after controlling for the covariate effects of gender, age, rate of seizure per week at enrollment, type of seizure and number of AEDs combinations used at enrollment. Results: Fifty-nine subjects (n=59) completed the study (59.6%).The average number of seizures per month were 9.7 ± 1.2 in the EPA group, 11.7 ± 1.5 in the DHA group, and 16.6 ± 1.5 in the placebo group. Age, gender and seizure type adjusted seizure incidence rate ratios (IRRs) of the EPA and DHA groups compared with the placebo were 0.61 (CI= 0.42-0.88, p=0.008, 42% reduction) and 0.67 (CI = 0.46-1.0, p= 0.04, 39% reduction), respectively. There was no difference in IRR between the EPA and DHA groups (p=0.56). Both treatment groups had a significantly higher number of seizure-free days compared to placebo (p<0.05).

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A minimum of 3 months of dietary fish oil supplementation is required to raise amygdaloid afterdischarge seizure thresholds in rats - implications for treating complex partial seizures

Cited by 25 publications

References 61 publications

Synergistic effect of docosahexaenoic acid on anticonvulsant activity of valproic acid and lamotrigine in animal seizure models

Synergistic effect of docosahexaenoic acid on anticonvulsant activity of valproic acid and lamotrigine in animal seizure models

Effect of Chronic Krill Oil Supplement on Seizures Induced by Pentylenetetrazole in the Hippocampus of Adult Rats with Previous Febrile Seizures

The differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on seizure frequency in patients with drug-resistant epilepsy — A randomized, double-blind, placebo-controlled trial

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