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Updated: Dec 18, 2025
Pentylenetetrazole-Induced Kindling Mouse Model
Published on: June 12, 2018
MS275 reduces seizure-induced brain damage in developing rats by regulating p38 MAPK signaling pathways and
Qing-Peng Hu1, Xiang-Yi Huang2, Fang Peng1
1Department of Pediatrics, The Second Hospital, University of South China, Hengyang, Hunan 421001, China.
Abstract:
Seizure is a common acute and severe disease in infants and children. Recurrent seizures or persistent seizures may cause irreversible brain damage. Mitogen activated protein kinase (MAPK) signaling pathway is associated with an inflammatory response, however it's involvement in the pathological process of seizures is not clear. Histone deacetylase inhibitors (HDACi) have promising neuroprotective effects through epigenetic regulation. Therefore, this study aimed to investigate the mechanism of HDACi MS275 on p38 MAPK signaling pathway and p38 histone modifications in developing rats post-seizure. Intraperitoneal administration of Pentylenetetrazole (PTZ) was used to induce developing rat seizures, and MS275 (5 or 10 mg/kg) was injected intraperitoneally 2 h before PTZ injection. Hippocampal tissues were sampled at 24 h post-seizures for protein and mRNA levels of p38、MK2、CREB and IL-6. Neuronal apoptosis and microglia activation significantly increased after PTZ treatment. However, pretreatment with MS275 attenuated these effects as well as increased seizure latency and decreased seizure scores. Furthermore, MS275 was found to inhibit the expression of p38 by increasing histone H3 and H4 acetylation and decreasing histone H3 and H4 methylation. This study thereby demonstrates that HDACi MS275 can reduce the inflammatory response associated with seizure-induced brain injury through inhibiting the p38 MAPK signaling pathway and p38 gene expression.
Insights
Histone deacetylase inhibitors (HDACi) like MS275 offer neuroprotection against seizures in developing rats. MS275 reduces brain inflammation and damage by inhibiting the p38 MAPK pathway.
Area of Science:
- Neuroscience
- Epigenetics
- Pharmacology
Background:
- Seizures in infants and children can cause severe, irreversible brain damage.
- The p38 Mitogen Activated Protein Kinase (MAPK) pathway's role in seizure pathology is unclear.
- Histone deacetylase inhibitors (HDACi) show potential neuroprotective effects via epigenetic regulation.
Purpose of the Study:
- To investigate the mechanism of HDAC inhibitor MS275 on the p38 MAPK pathway and histone modifications in developing rats after induced seizures.
- To evaluate MS275's neuroprotective effects against seizure-induced brain injury.
Main Methods:
- Induced seizures in developing rats using Pentylenetetrazole (PTZ).
- Administered MS275 (5 or 10 mg/kg) intraperitoneally before PTZ.
- Analyzed hippocampal tissues for protein and mRNA levels of p38, MK2, CREB, and IL-6.
- Assessed neuronal apoptosis and microglia activation.
Main Results:
- PTZ treatment increased neuronal apoptosis and microglia activation.
- MS275 pretreatment attenuated these effects, increased seizure latency, and decreased seizure scores.
- MS275 inhibited p38 expression by increasing histone H3/H4 acetylation and decreasing H3/H4 methylation.
Conclusions:
- HDACi MS275 demonstrates neuroprotective effects in a rat seizure model.
- MS275 mitigates seizure-induced brain inflammation by inhibiting the p38 MAPK signaling pathway.
- Epigenetic modification of histone acetylation and methylation by MS275 underlies its therapeutic potential.
