The survival of microglia depends on the colony-stimulating factor-1 receptor (CSF1R) signaling pathway under physiological conditions.
Ki20227 is a highly selective CSF1R inhibitor that has been shown to change the morphology of microglia. However, the effects of
Ki20227 on the progression of
ischemic stroke are unclear. In this study, male C57BL/6 mouse models of focal cerebral ischemic injury were established through the occlusion of the middle cerebral artery and then administered 3 mg/g
Ki20227 for 3 successive days. The results revealed that the number of ionized
calcium-binding adaptor molecule 1/
bromodeoxyuridine double positive cells in the
infarct tissue was reduced, the degree of
edema was increased, neurological deficits were aggravated,
infarct volume was increased, and the number of peri-
infarct Nissl bodies was reduced. The number of
terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in the peri-
infarct tissue was increased. The expression levels of Bax and Cleaved
caspase-3 were up-regulated. Bcl-2 expression was downregulated. The expression levels of inflammatory factors and oxidative stress-associated factors were increased. These findings suggested that
Ki20227 blocked microglial proliferation and aggravated the pathological progression of
ischemia/reperfusion injury in a transient
middle cerebral artery occlusion model. This study was approved by the Animal Ethics Committee of Lanzhou University Second Hospital (approval No. D2020-68) on March 6, 2020.