Curcumin attenuated neuroinflammation via the TLR4/MyD88/NF-κB signaling way in the juvenile rat hippocampus following kainic acid-induced epileptic seizures.

The study examined curcumin's impart on relieving neuroinflammation of juvenile rats in kainic acid (KA) induced epileptic seizures by inhibiting the TLR4/MyD88/NF-κB pathway. There were five groups: control, KA, KA + curcumin (KC), KA + oxcarbazepine (OXC) (KO), KA + curcumin + OXC (KCO) groups. KA was stereotactically injected into right hippocampus following intraperitoneal injection of curcumin or (and) OXC for seven days. The rats in the above groups were randomly divided into three subgroups (at 6 h, 24 h, and 72 h of KA administration) following the seizure degree assessed. The number of NeuN (+) neurons and GFAP (+) astrocytes was counted. The gene and protein levels of TLR4, MyD88, and NF-κB were detected. Compared with the KA group, the seizure latency was longer, and the incidence of status epilepticus (SE) was lower in the KC, KO, and KCO groups. The most significant changes were in the KCO group. At 72 h following KA injected, the number of neurons was the least, and the number of astrocytes was the most in the KA group. The number of neurons was the most and the number of astrocytes was the least in the KCO group. At 24 h, the mRNA and protein levels of TLR4, MyD88, and NF-κB in the KA group were the most. The above valves were the least in the KCO group. Therefore, curcumin could enhance anti-epileptic effect of OXC, protect injured neurons and reduce proliferated glial cells of the hippocampus of epileptic rats by inhibiting inflammation via the TLR4/MyD88/NF-κB pathway.

Silencing miR-155-5p alleviates hippocampal damage in kainic acid-induced epileptic rats via the Dusp14/MAPK pathway.

Epilepsy with recurrent seizures is characterized by neuronal damage and glial proliferation induced by brain inflammation. Recurrent seizures can lead to changes in the microRNA (miRNA) spectrum, significantly influencing the inflammatory response of microglia. MiR-155-5p, as a pro-inflammatory miRNA, is increased in the epileptic brain. However, its specific role in acute seizures remains unknown. The study aimed to develop a new strategy for treating epilepsy by investigating how silencing of miR-155-5p initiated its anticonvulsive mechanism. The level of miR-155-5p was up-regulated in the hippocampus of epileptic immature rats induced by kainic acid (KA). The use of antago-miR-155-5p exerted significant beneficial effects on the seizure scores, brain discharges and cognition in immature rats following KA-induced epilepsy. Antago-miR-155-5p also inhibited neuron damage and microglial activation. Moreover, the silencing of miR-155-5p significantly inhibited the Dual-specificity phosphatase 14 (Dusp14)/ mitogen-activated protein kinase (MAPK) axis in vivo. MiR-155-5p interacted with dusp14 to regulate MAPK signaling way expression, verified by a dual-luciferase reporter assay. The results suggested that the silencing of miR-155-5p might reduce hippocampal damage in epileptic immature rats induced by KA via Dusp14/MAPK signaling way. This implied that miR-155-5p could serve as a therapeutic tool to prevent the development of epilepsy.