Effects of linoleic acid on generalized convulsive and nonconvulsive epileptic seizures

Ekici, Filiz; Gürol, Gönül; Ateş, Nurbay

doi:10.3906/sag-1305-13

Cited by 9 publications

(5 citation statements)

References 13 publications

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“…When infused intravenously at a dose of 0.028 mg/kg, it decreased the incidence of tonic-clonic convulsions by 3-fold, but increased the incidence of cortical spike-wave discharges by 1.5 to 2 folds. 32 Voskuyl et al showed that intravenous administration of 56–64 mg/kg LA raised cortical focal and generalized seizure thresholds by 3-fold and 1.3–9.0-fold, respectively, in a cortical stimulation seizure model compared to saline and oleic acid controls. 33 The effect of chronic LA administration on seizure thresholds has not been tested.…”

Section: Effects Of La or Oxlams On Rodentsmentioning

confidence: 99%

Linoleic acid–good or bad for the brain?

Taha

2020

npj Sci Food

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Increased intake of omega-6 rich plant oils such as soybean and corn oil over the past few decades has inadvertently tripled the amount of n-6 linoleic acid (LA, 18:2n-6) in the diet. Although LA is nutritionally “essential”, very little is known about how it affects the brain when present in excess. This review provides an overview on the metabolism of LA by the brain and the effects of excess dietary LA intake on brain function. Pre-clinical evidence suggests that excess dietary LA increases the brain’s vulnerability to inflammation and likely acts via its oxidized metabolites. In humans, excess maternal LA intake has been linked to a typical neurodevelopment, but underlying mechanisms are unknown. It is concluded that excess dietary LA may adversely affect the brain. The potential neuroprotective role of reducing dietary LA merits clinical evaluation in future studies.

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Section: Effects Of La or Oxlams On Rodentsmentioning

confidence: 99%

Linoleic acid–good or bad for the brain?

Taha

2020

npj Sci Food

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“…However, very little is known about the role of LA or its metabolites in brain. LA was reported to raise seizure threshold in rats 50, 51 , and to increase the number and duration of spontaneous wave discharges in a rat model of absence seizures 51 , suggesting its involvement in neurotransmission. Although it is not known whether the effects of LA in brain are mediated by LA itself or its oxidized metabolites, LA-metabolites have been detected in brain tissue 31, 52 and are known to activate pain-gating transient receptor potential vanilloid (TRPV) channels and inflammatory pathways in rodent spinal cord 53 and hindpaw 54 , and to reduce retinal epithelial cell growth 55 .…”

Section: Introductionmentioning

confidence: 94%

Linoleic acid participates in the response to ischemic brain injury through oxidized metabolites that regulate neurotransmission

Hennebelle

Zhang

Metherel

et al. 2017

Sci Rep

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Linoleic acid (LA; 18:2 n-6), the most abundant polyunsaturated fatty acid in the US diet, is a precursor to oxidized metabolites that have unknown roles in the brain. Here, we show that oxidized LA-derived metabolites accumulate in several rat brain regions during CO2-induced ischemia and that LA-derived 13-hydroxyoctadecadienoic acid, but not LA, increase somatic paired-pulse facilitation in rat hippocampus by 80%, suggesting bioactivity. This study provides new evidence that LA participates in the response to ischemia-induced brain injury through oxidized metabolites that regulate neurotransmission. Targeting this pathway may be therapeutically relevant for ischemia-related conditions such as stroke.

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“…Linoleic acid is a polyunsaturated fatty acid, and previous studies have suggested that it has a protective effect against seizures. Ekici et al found that linoleic acid combined with conventional antiepileptic drugs had a positive effect on generalized epilepsy 33 . In a recent meta‐analysis, Asadi‐Pooya et al found the addition of linoleic acid was beneficial in controlling seizures 34 .…”

Section: Discussionmentioning

confidence: 99%

“…Ekici et al found that linoleic acid combined with conventional antiepileptic drugs had a positive effect on generalized epilepsy. 33 In a recent meta‐analysis, Asadi‐Pooya et al found the addition of linoleic acid was beneficial in controlling seizures. 34 In our study, we found that the non‐responsive group had lower levels of linoleic acid, a phenomenon that might be related to poor spasm control.…”

Section: Discussionmentioning

confidence: 99%

Abnormalities in Clostridioides and related metabolites before ACTH treatment may be associated with its efficacy in patients with infantile epileptic spasm syndrome

Wan

Shi

et al. 2023

CNS Neurosci Ther

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ObjectiveAdrenocorticotropic hormone (ACTH) is the first‐line treatment of infantile epileptic spasm syndrome (IESS). Its reported effectiveness varies, and our current understanding regarding the role of gut microbiota composition in IESS treatment response is limited. This study assessed the microbiome–metabolome association to understand the role and mechanism of gut microbiota composition in IESS treatment outcomes.MethodsChildren with IESS undergoing ACTH treatment were enrolled. Pre‐treatment stool and serum samples were collected for 16S rRNA gene sequencing and liquid chromatography–tandem mass spectrometry, respectively. The children were divided into “responsive” and “non‐responsive” groups, and gut microbiota and serum metabolome differences were analyzed.ResultsOf the 30 patients with IESS, 14 responded to ACTH and 16 did not. The “non‐responsive” group had larger maleficent Clostridioides and Peptoclostridium_phage_p630P populations (linear discriminant analysis >2; false discovery rate q < 0.05). Ten metabolites were upregulated (e.g., xanthurenic acid) and 15 were downregulated (e.g., vanillylmandelic acid) (p < 0.05). Association analysis of the gut microbiome and serum metabolome revealed that Clostridioides and Peptoclostridium_phage_p630P2 were positively correlated with linoleic and xanthurenic acids, while Clostridioides was negatively correlated with vanillylmandelic acid (p < 0.05). A classifier using differential gut bacteria and metabolites achieved an area under the receiver operating characteristic curve of 0.906 to distinguish responders from non‐responders.ConclusionThis study found significant differences in pre‐treatment gut microbiota and serum metabolome between children with IESS who responded to ACTH and those who did not. Additional exploration may provide valuable information for treatment selection and potential interventions. Our results suggest that varying ACTH responses in patients with IESS may be associated with increased gut Clostridioides bacteria and kynurenine pathway alteration, but additional experiments are needed to verify this association.

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Effects of linoleic acid on generalized convulsive and nonconvulsive epileptic seizures

Cited by 9 publications

References 13 publications

Linoleic acid–good or bad for the brain?

Linoleic acid–good or bad for the brain?

Linoleic acid participates in the response to ischemic brain injury through oxidized metabolites that regulate neurotransmission

Abnormalities in Clostridioides and related metabolites before ACTH treatment may be associated with its efficacy in patients with infantile epileptic spasm syndrome

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