Combination of early and delayed ischemic postconditioning enhances brain-derived neurotrophic factor production by upregulating the ERK-CREB pathway in rats with focal ischemia

Autor: Shao‑Feng Yang, Xiaohua Zhang, Yi‑Feng Miao, Hui Wu, Jiong Dai, Yong‑Ming Qiu
Rok vydání: 2015
Předmět:
Male
Cancer Research
Pathology
medicine.medical_specialty
Time Factors
MAP Kinase Signaling System
Apoptosis
Brain Edema
Pharmacology
CREB
focal brain ischemia
Biochemistry
Brain Ischemia
Rats
Sprague-Dawley
Brain ischemia
Neurotrophic factors
Genetics
medicine
Animals
ischemic postconditioning
Cyclic AMP Response Element-Binding Protein
Molecular Biology
Stroke
combination
Cerebral Cortex
Mitogen-Activated Protein Kinase 1
Neurons
Brain-derived neurotrophic factor
Mitogen-Activated Protein Kinase 3
TUNEL assay
biology
business.industry
Brain-Derived Neurotrophic Factor
Infarction
Middle Cerebral Artery
Articles
medicine.disease
Rats
medicine.anatomical_structure
Gene Expression Regulation
Oncology
Cerebral blood flow
Cerebral cortex
Astrocytes
biology.protein
Molecular Medicine
neuroprotection
business
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
1791-2997
DOI: 10.3892/mmr.2015.4327
Popis: Ischemic postconditioning, including early and delayed ischemic postconditioning, has been recognized as a simple and promising strategy in the treatment of stroke. However, the effects of the combination of early and delayed ischemic postconditioning, and the mechanisms underlying these effects, remain unclear. The aim of the present study was to determine whether the combination of early and delayed ischemic postconditioning offers greater protection against stroke, and enhances the production of brain‑derived neurotrophic factor (BDNF). A combination of early and delayed ischemic postconditioning was established by repeated, transient occlusion and reperfusion of the ipsilateral common carotid artery in a rat model of middle cerebral artery occlusion. Infarct size, motor function, cerebral blood flow and brain edema were then evaluated, in order to confirm the effects of combinative ischemic postconditioning. TUNEL staining was used to analyze the rate of apoptosis of cells in the penumbral area. BDNF, extracellular signal‑regulated kinases 1/2 (ERK1/2) and cAMP response element‑binding protein (CREB) expression was detected using immunofluorescence staining and western blot analysis. The results of the present study indicated that the combination of early and delayed ischemic postconditioning further reduced the infarct volume, stabilized cerebral blood disturbance and attenuated neuronal apoptosis, compared with either alone. However, combinative postconditioning exerted the same effect on neurological function and brain edema, compared with early or delayed ischemic postconditioning alone. Further investigation indicated that combinative ischemic postconditioning increased the expression of BDNF, and a significantly higher number of BDNF‑positive cells was observed in neurons and astrocytes from the combined group than in the early or delayed groups. Combinative ischemic postconditioning also induced the phosphorylation of ERK1/2 and CREB in the cortex, following focal ischemia. The results of the present study suggest that the combination of early and delayed ischemic postconditioning may further reduce brain ischemic reperfusion injury following focal ischemia, compared with either treatment alone. In addition, it induces the production of BDNF in neurons and astrocytes. Furthermore, the effects of combinative ischemic postconditioning may be mediated by the activation of ERK1/2 and CREB.
Databáze: OpenAIRE
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