This study aims to evaluate the potential effect and the underlying mechanism of CCL2 in ischemic stroke.
An integrated bioinformatics analysis was performed to identify the differentially expressed (DE) genes and their related pathways in ischemic stroke. En vivo study of a rat model of middle cerebral artery occlusion (MCAO) was further established to assess the effect of C-C Motif Chemokine Ligand 2 (CCL2) on severity of neurologic impairments. The expression levels of pro-inflammatory cytokines were also evaluated using the ELISA assay, and western blot was also used to determine the expression of CCL2 and other DE proteins in the related pathways.
A total of 88 DE genes were identified from the microarray dataset of ischemic stroke. The bioinformatic analysis revealed that CCL2 was highly expressed in ischemic stroke tissues and promoted the ischemic stroke progression via activation of the chemokine signaling pathway and cytokine-cytokine receptor interaction pathway. The in vivo study of the ischemic stroke rat model also showed that the CCL2 expression was elevated in the MCAO/R rats; with significant neurological impairments and ischemic infarct area in the brain tissues being observed. The administration of CCL2 inhibitors significantly inhibited the inflammatory response, attenuated the neurological impairments and decreased the ischemic infarct area in the MCAO/R rats. Furthermore, the down regulation of CCL2 also inhibited the expression of the pathway related proteins including CCL7, CCR2, CXCL16 and TNF-α.
These results indicate that the CCL2/chemokine signaling pathway is responsible for ischemic stroke progression and might represent a potential therapeutic target for ischemic stroke treatment.

Copyright © 2020. Published by Elsevier Inc.

References

PubMed