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Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R/PLCG2/PKA/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE
- Source :
- Oxidative Medicine and Cellular Longevity, Oxidative Medicine and Cellular Longevity, Vol 2020 (2020)
- Publication Year :
- 2020
-
Abstract
- Oxidative stress (OS) and neuronal apoptosis are major pathological processes after hypoxic-ischemic encephalopathy (HIE). 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 h. Exogenous recombinant human CSF1 (rh-CSF1) was administered intranasally at 1 h and 24 h after HI. The CSF1R inhibitor, BLZ945, or phospholipase C-gamma 2 (PLCG2) inhibitor, U73122, was injected intraperitoneally at 1 h 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 h 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.
- Subjects :
- Aging
medicine.medical_specialty
Article Subject
Apoptosis
Brain damage
medicine.disease_cause
Biochemistry
Neuroprotection
Rats, Sprague-Dawley
Western blot
Internal medicine
medicine
Animals
Humans
Uncoupling Protein 2
Benzothiazoles
Receptor
Picolinic Acids
Neurons
TUNEL assay
QH573-671
medicine.diagnostic_test
Chemistry
Phospholipase C gamma
Macrophage Colony-Stimulating Factor
Cell Biology
General Medicine
Cyclic AMP-Dependent Protein Kinases
Recombinant Proteins
Rats
Up-Regulation
Disease Models, Animal
Oxidative Stress
Endocrinology
Neuroprotective Agents
Proto-Oncogene Proteins c-bcl-2
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
Hypoxia-Ischemia, Brain
Signal transduction
medicine.symptom
Cytology
Oxidative stress
Signal Transduction
Research Article
Subjects
Details
- ISSN :
- 19420994
- Volume :
- 2020
- Database :
- OpenAIRE
- Journal :
- Oxidative medicine and cellular longevity
- Accession number :
- edsair.doi.dedup.....bb1829ae489801fde6c1d066e68bc122