Bindarit attenuates neuroinflammation after subarachnoid hemorrhage by regulating the CCL2/CCR2/NF-κB pathway

The poor prognosis of subarachnoid hemorrhage (SAH) is closely linked to neuroinflammation and neuronal apoptosis. The CCL2/CCR2 signaling axis, a cytoplasmic pathway responsible for recruiting immune cells, plays a significant role in regulating neuroinflammation in neurological diseases. Bindarit, an inhibitor of chemokine CC motif ligand 2(CCL2), has been shown to demonstrate neuroprotective effects in various central nervous system diseases. This study aimed to investigate the anti-inflammatory effects of Bindarit after SAH.

Pre-processed RNA-seq transcriptome datasets GSE79416 from the Gene Expression Omnibus (GEO) database were analyzed to identify genes differentially expressed between mice with SAH and control mice using bioinformatics methods. Bindarit, a CCL2 inhibitor, was administered intraperitoneally one hour after SAH. Recombinant CCL2 protein was administered via the lateral ventricle one hour before SAH induction. HT22 cells were cultured and stimulated by oxyhemoglobin to establish an in vitro model of SAH.

Analysis of GSE79416 datasets revealed upregulation of CCL2 expression, identifying it as a hub gene in SAH. Following SAH, CCL2 expression increased in rat brain tissue, reaching the highest level 24 h after SAH. Bindarit improved the short-term and long-term neurological deficits after SAH and also exhibited the anti-inflammatory effects following SAH. Conversely, administration of recombinant CCL2 protein attenuated the protective effects of Bindarit. In vitro, Bindarit significantly reduced neuronal inflammation.

Endogenous CCL2 expression was upregulated in the rat SAH model. Bindarit improved neurological functions and reduced neuroinflammation by regulating the CCL2/CCR2/NF-κB pathway in early brain injury after SAH.