Propagermanium, a CCR2 inhibitor, attenuates cerebral ischemia/reperfusion injury through inhibiting inflammatory response induced by microglia

Publication date: Available online 19 February 2019Source: Neurochemistry InternationalAuthor(s): Shucheng He, Rui Liu, Binbin Li, Liangliang Huang, Wenxiang Fan, Charmaine Ruvimbo Tembachako, Xiaoya Zheng, Xiaoxing Xiong, Masaaki Miyata, Baohui Xu, Yunman Li, Weirong FangAbstractCCR2 could recruit immune cells migrating into brain after ischemic stroke. It is unclear whether and why Propagermanium (PG, a CCR2 inhibitor) is able to protect against ischemic injury. Middle cerebral artery occlusion (MCAO) and reperfusion injury in C57BL/6 J male mice were performed in vivo to mimic ischemic stroke. Cultured BV2 microglia exposed to oxygen and glucose deprivation (OGD)/reoxygenation injury, LPS or IL-4 incubation were served in vitro. TTC staining, neurological score, brain water content, and MRI scan were performed to evaluate stroke outcome. Real time PCR, ELISA, and immunofluorescence were used to estimate inflammatory cytokines expression and releasing. Western blot was utilized to detect pSTAT1/STAT1 expression. Compared with MCAO mice, PG treatment significantly reduced infarction size and brain edema, improved neurological behavior at 72 h after MCAO. For inflammatory response, PG treatment inhibited inflammatory cytokines releasing, such as TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-17, and IL-23. Further studies indicated that PG treatment downregulated mRNA expression of pro-inflammatory iNOS and CD86, and inhibited CD16 expressed in microglia. In vitro, PG incubation...
Source: Neurochemistry International - Category: Neuroscience Source Type: research