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Updated: Aug 19, 2025
A Model of Epileptogenesis in Rhinal Cortex-Hippocampus Organotypic Slice Cultures
Published on: March 18, 2021
Microglial activation and over pruning involved in developmental epilepsy
Qiong Wu1, Hua Wang1, Xueyan Liu1
1Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
Abstract:
To understand the potential role of microglia in synaptic pruning following status epilepticus (SE), we examined the time course of expression of Iba-1, and immune and neuroinflammatory regulators, including CD86, CD206, and CX3CR1, and TLR4/NF-κB after SE induced by pilocarpine in rats. Behavioral tests, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, immunohistochemical staining, Western blotting, PCR, and fluorescence double staining assessments were performed. The expression of Iba-1 protein was lowest in the control group, and peaked after 2 days (p < 0.001). CD86 and CD206 mRNA levels increased gradually in the microglia of the epilepsy group after 12 hours, 1 day, 2 days, and 3 days; peak expression was on the second day. The expression of the chemokine receptor CX3CR1 in microglia increased to varying degrees after SE, and expression of the presynaptic protein synapsin decreased. The expression of TLR4/NF-κB in microglia positively correlated with Iba-1 protein expression. These findings indicate that the TLR4/NF-κB signaling pathway may be involved in the activation and polarization of microglia in epilepsy and in excess synaptic pruning, which could lead to an increase in brain injury.
Insights
Microglia activation, indicated by Iba-1 expression, and immune regulators CD86, CD206, and CX3CR1 increase after status epilepticus (SE). The TLR4/NF-κB pathway may drive excessive synaptic pruning and brain injury in epilepsy.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia play a crucial role in brain homeostasis and disease.
- Status epilepticus (SE) is a neurological emergency characterized by prolonged seizures.
- Synaptic pruning is a vital process for neural circuit development and plasticity.
Purpose of the Study:
- To investigate the role of microglia in synaptic pruning following status epilepticus (SE).
- To examine the time course of microglial activation and immune/neuroinflammatory regulator expression after SE.
- To elucidate the involvement of the TLR4/NF-κB signaling pathway in epilepsy-induced microglial responses.
Main Methods:
- Pilocarpine-induced SE in a rat model.
- Behavioral tests, TUNEL staining, immunohistochemistry, Western blotting, and PCR.
- Analysis of Iba-1, CD86, CD206, CX3CR1, TLR4/NF-κB, and synapsin expression.
Main Results:
- Iba-1 protein expression peaked at 2 days post-SE.
- CD86 and CD206 mRNA levels increased, peaking on day 2.
- CX3CR1 expression in microglia increased, while presynaptic protein synapsin decreased post-SE.
- TLR4/NF-κB expression positively correlated with Iba-1, suggesting pathway involvement.
Conclusions:
- Microglial activation and altered immune profiles are prominent after SE.
- The TLR4/NF-κB signaling pathway is implicated in microglial activation and polarization in epilepsy.
- Excessive synaptic pruning, potentially mediated by activated microglia, may contribute to brain injury in epilepsy.
