CNS Neurosci Ther. 2023 Jan;29(1):317-330.doi: 10.1111/cns.14006. Epub 2022 Nov 28.

本文采用的英格恩产品: RNA-Entranster-invivo

Targeting CCL5 signaling attenuates neuroinflammation after seizure

Zhuoran Zhang  1   2 Yan Li  1 Shihe Jiang  1 Fu-Dong Shi  1   2 Kaibin Shi  1 Wei-Na Jin  1

Affiliations

Affiliations

  • 1 China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
  • 2 Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China.

Free PMC article

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.

Keywords: CCL5; CCR5; maraviroc; seizure; spatial transcriptomics.

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