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Colony stimulating factor 1 (CSF1), binding to CSF1 receptor (CSF1R), has been shown to reduce neuronal loss after hypoxic-ischemia- (HI-) induced brain injury. In the present study, we hypothesized that CSF1 could alleviate OS-induced neuronal degeneration and apoptosis through the CSF1R\/PLCG2\/PKA\/UCP2 signaling pathway in a rat model of HI. A total of 127 ten-day old Sprague Dawley rat pups were used. HI was induced by right common carotid artery ligation with subsequent exposure to hypoxia for 2.5\u2009h. Exogenous recombinant human CSF1 (rh-CSF1) was administered intranasally at 1\u2009h and 24\u2009h after HI. The CSF1R inhibitor, BLZ945, or phospholipase C-gamma 2 (PLCG2) inhibitor, U73122, was injected intraperitoneally at 1\u2009h before HI induction. Brain infarct volume measurement, cliff avoidance test, righting reflex test, double immunofluorescence staining, western blot assessment, 8-OHdG and MitoSOX staining, Fluoro-Jade C staining, and TUNEL staining were used. Our results indicated that the expressions of endogenous CSF1, CSF1R, p-CSF1R, p-PLCG2, p-PKA, and uncoupling protein2 (UCP2) were increased after HI. CSF1 and CSF1R were expressed in neurons and astrocytes. Rh-CSF1 treatment significantly attenuated neurological deficits, infarct volume, OS, neuronal apoptosis, and degeneration at 48\u2009h after HI. Moreover, activation of CSF1R by rh-CSF1 significantly increased the brain tissue expressions of p-PLCG2, p-PKA, UCP2, and Bcl2\/Bax ratio, but reduced the expression of cleaved caspase-3. The neuroprotective effects of rh-CSF1 were abolished by BLZ945 or U73122. These results suggested that rh-CSF1 treatment attenuated OS-induced neuronal degeneration and apoptosis after HI, at least in part, through the CSF1R\/PLCG2\/PKA\/UCP2 signaling pathway. Rh-CSF1 may serve as therapeutic strategy against brain damage in patients with HIE.<\/jats:p>","DOI":"10.1155\/2020\/6801587","type":"journal-article","created":{"date-parts":[[2020,10,11]],"date-time":"2020-10-11T08:55:31Z","timestamp":1602406531000},"page":"1-20","source":"Crossref","is-referenced-by-count":32,"title":["Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R\/PLCG2\/PKA\/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE"],"prefix":"10.1155","volume":"2020","author":[{"given":"Xiao","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People's Hospital, Guiyang 550002, China"},{"name":"Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People's Hospital, Guiyang 550002, 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