Curcumin reduces development of seizurelike events in the hippocampal‐entorhinal cortex slice culture model for epileptogenesis

Abstract

Summary Objective Inhibition of the mammalian target of rapamycin (mTOR) pathway could be antiepileptogenic in temporal lobe epilepsy (TLE), possibly via anti‐inflammatory actions. We studied effects of the mTOR inhibitor rapamycin and the anti‐inflammatory compound curcumin—also reported to inhibit the mTOR pathway—on epileptogenesis and inflammation in an in vitro organotypic hippocampal‐entorhinal cortex slice culture model. Methods Brain slices containing hippocampus and entorhinal cortex were obtained from 6‐day‐old rat pups and maintained in culture for up to 3 weeks. Rapamycin or curcumin was added to the culture medium from day 2 in vitro onward. Electrophysiological recordings revealed epileptiformlike activity that developed over 3 weeks. Results In week 3, spontaneous seizurelike events (SLEs) could be detected using whole cell recordings from CA1 principal neurons. The percentage of recorded CA1 neurons displaying SLEs was lower in curcumin‐treated slice cultures compared to vehicle‐treated slices (25.8% vs 72.5%), whereas rapamycin did not reduce SLE occurrence significantly (52%). Western blot for phosphorylated‐S6 (pS6) and phosphorylated S6K confirmed that rapamycin inhibited the mTOR pathway, whereas curcumin only lowered pS6 expression at one phosphorylation site. Real‐time quantitative polymerase chain reaction results indicated a trend toward lower expression of inflammatory markers IL‐1β and IL‐6 and transforming growth factor β after 3 weeks of treatment with rapamycin and curcumin compared to vehicle. Significance Our results show that curcumin suppresses SLEs in the combined hippocampal‐entorhinal cortex slice culture model and suggest that its antiepileptogenic effects should be further investigated in experimental models of TLE.

Electrical stimulation of the endopiriform nucleus attenuates epilepsy in rats by network modulation

“…Altered dynamics of the stimulated network, recalibrating dysfunctional circuits, maybe a core mechanism of DBS 53 . Our results showed that the effect of LFS‐EPN on hippocampus seizure control was better than that of motor cortex, which may be due to denser EPN connectivity with entorhinal cortex, 6,40 resulting in greater modulation of the temporal lobe than the motor cortex 54,55 . EPN may be involved in the propagation and generalization of seizures originating from the motor cortex to the hippocampus.…”

“…53 Our results showed that the effect of LFS-EPN on hippocampus seizure control was better than that of motor cortex, which may be due to denser EPN connectivity with entorhinal cortex, 6,40 resulting in greater modulation of the temporal lobe than the motor cortex. 54,55 EPN may be involved in the propagation and generalization of seizures originating from the motor cortex to the hippocampus. Anatomical evidence does not demonstrate efferent projections from EPN to the structures in the contralateral hemisphere of the brain.…”

<p>Liposomal Encapsulated Curcumin Effectively Attenuates Neuroinflammatory and Reactive Astrogliosis Reactions in Glia Cells and Organotypic Brain Slices</p>

“…In comparable brain slice models, curcumin has previously been shown to protect from Aβ1-42-induced toxicity, to prevent cell death as well as bilirubin-induced cell damage, and to reduce seizure-like events. [84][85][86][87][88] In our brain slice model, we could show that our liposomal curcumin formulation could alleviate cytotoxic effects of LPS stimulations, induction of pro-inflammatory cytokines and genes associated with reactive astrogliosis and restore cellular loss, being at least as effective as free curcumin. Thus, we could show in two different test systems (even from different species) that liposomal encapsulated curcumin (LipoCur) can effectively prevent reactive processes that occur in glial scar formation.…”

The Gelatinase Inhibitor ACT-03 Reduces Gliosis in the Rapid Kindling Rat Model of Epilepsy, and Attenuates Inflammation and Loss of Barrier Integrity In Vitro

“…Persistent activation of astrocytes and microglia may lead to a pro-inflammatory environment, which has been implicated in the development of many neurological disorders including several types of epilepsies [ 42 , 43 ]. Activation of astrocyte and microglia and increased expression of their signature markers has been shown after brain insults such as a status epilepticus, induced seizures or brain trauma [ 43 , 44 , 45 , 46 , 47 ]. Staining for the commonly used marker for astrogliosis, GFAP, did not show a difference between vehicle-treated and ACT-03-treated kindled rats.…”