Dataset Information

Targeting CCL5 signaling attenuates neuroinflammation after seizure.

ABSTRACT:

Background

Epilepsy is a neurological condition that causes unprovoked, recurrent seizures. Accumulating evidence from clinical and experimental studies indicates that neuroinflammation exacerbates seizure activity.

Methods

We investigated the transcriptional changes occurring in specific brain domains of a seizure mouse model, using 10× Genomics spatial transcriptomics. Differential gene expression and pathway analysis were applied to investigate potential signaling targets for seizure, including CCL5/CCR5 pathway. Maraviroc, an FDA-approved C-C chemokine receptor 5 (CCR5) antagonist, was used to verify the impact of CCL5/CCR5 signaling in seizure mice.

Results

We found distinguished regional transcriptome features in the hippocampus of seizure mice. The hippocampus exhibited unique inflammatory gene signatures, including glia activation, apoptosis, and immune response in seizure mice. Especially, we observed notable expression of C-C chemokine ligand 5 (CCL5) throughout the entire seizure hippocampus. Blockade of CCL5/CCR5 signaling via maraviroc prevented microglia activation and neuron degeneration in seizure mice.

Conclusions

This study supports the potential of CCL5/CCR5 signaling for targeting neuroinflammation after seizure.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC9804050 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Targeting CCL5 signaling attenuates neuroinflammation after seizure.

Zhang Zhuoran Z Li Yan Y Jiang Shihe S Shi Fu-Dong FD Shi Kaibin K Jin Wei-Na WN

CNS neuroscience & therapeutics 20221128 1

<h4>Background</h4>Epilepsy is a neurological condition that causes unprovoked, recurrent seizures. Accumulating evidence from clinical and experimental studies indicates that neuroinflammation exacerbates seizure activity.<h4>Methods</h4>We investigated the transcriptional changes occurring in specific brain domains of a seizure mouse model, using 10× Genomics spatial transcriptomics. Differential gene expression and pathway analysis were applied to investigate potential signaling targets for s ...[more]

PMID: 36440924

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Dataset Information

Targeting CCL5 signaling attenuates neuroinflammation after seizure.

Background

Methods

Results

Conclusions

Publications

Targeting CCL5 signaling attenuates neuroinflammation after seizure.

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