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 morp...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 C57 BL/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.展开更多
基金supported by the Natural Science Foundation of Gansu Province,China,Nos.20JR5RA337(to BRH),20JR5RA336(to HJR)Cuiying Graduate Supervisor Applicant Training Program of Lanzhou University Second Hospital,China,No.CYDSPY201902(to BRH)+1 种基金Cuiying Students Research Ability Training Program of Lanzhou University Second Hospital,China,No.CYXZ2020-14(to BRH)Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital,China,No.CY2018-MS08(to BRH)。
文摘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 C57 BL/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.
