Conclusions
Intravenous injection of IMRCs protected against CCH-induced white matter injury and cognitive impairment inhibition of microglial activation and regulation of microglia polarization.
Methods
A chronic cerebral hypoperfusion (CCH) model was established in rats via permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO). The rats then received intravenous injections of IMRCs or saline. A single injection of different doses of IMRCs (1 × 106 cells/rat, 2 × 106 cells/rat, or 4 × 106 cells/rat) was administered via tail vein 72 h after establishment of the model. To evaluate functional recovery, the rats were subjected to behavioural tests after 30 days of CCH. Imaging, western blotting, immunofluorescence staining, and quantitative real-time PCR were used to analyse neuroinflammation and white matter injury after 14 and 40 days of CCH. RNA sequencing (RNA-seq) was used to profile gene expression changes in copine 1 (CPNE1) in response to IMRCs treatment.
Results
Intravenous injection of 4 × 106 IMRCs alleviated white matter damage and ameliorated cognitive deficits in rats subjected to CCH. Immunofluorescence staining suggested that activation of microglia and astrocytes was reduced, and RNA sequencing showed that CPNE1 expression was significantly elevated following treatment with IMRCs. Conclusions: Intravenous injection of IMRCs protected against CCH-induced white matter injury and cognitive impairment inhibition of microglial activation and regulation of microglia polarization.