Intranasal Calcitonin Gene-Related Peptide Protects Against Focal Cerebral Ischemic Injury in Rats Through the Wnt/β-Catenin Pathway
| Autor: | Yongfeng Gao, Qiang Chen, Haidong Zhang, Baoliang Sun, Zhenlan Du |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Calcitonin
Male Vascular Endothelial Growth Factor A 0301 basic medicine Calcitonin Gene-Related Peptide Apoptosis Calcitonin gene-related peptide Pharmacology Brain Ischemia 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Ischemia Animals Rats Wistar Wnt Signaling Pathway Administration Intranasal beta Catenin TUNEL assay Cell growth Chemistry Animal Study Wnt signaling pathway Brain Cell cycle process Infarction Middle Cerebral Artery General Medicine Cerebral Arteries Rats Vascular endothelial growth factor Disease Models Animal Neuroprotective Agents 030104 developmental biology Real-time polymerase chain reaction nervous system Blood-Brain Barrier Ischemic Attack Transient Brain Injuries Reperfusion Injury 030217 neurology & neurosurgery |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 |
| DOI: | 10.12659/msm.913777 |
| Popis: | BACKGROUND Intranasal calcitonin gene-related peptide (CGRP) delivery offers a noninvasive method of bypassing the blood-brain barrier for the delivery of CGRP to the brain. Here, we first reported the therapeutic benefits of intranasal CGRP delivery in rats following middle cerebral artery occlusion (MCAO). MATERIAL AND METHODS Real-time quantitative polymerase chain reaction (RT-qPCR) assay, enzyme-linked immunosorbent assay (ELISA), rat MCAO model, TTC (2, 3, 5-triphenyltetrazolium chloride) staining, hematoxylin and eosin (H & E) staining, Morris water maze test, TUNEL assay, immunofluorescence, and western blot assay were used to investigate the role of CGRP in rats. Cell Counting Kit-8 assay, colony formation assay, cell cycle assay, apoptosis assay, western blot assay, and TOP/FOP assay were used to investigate the role of CGRP in normal human astrocytes (NHA) cells. RESULTS The CGRP-MCAO-NDDS (nasal drug delivery system) group showed a significant reduction in the infarct volume and improvement in neurologic deficit tests of motor, sensory, reflex and vestibulo-motor functions compared to those rats in the CGRP-MCAO-IV group. CGRP markedly inhibited apoptosis and increased the expression of vascular endothelial growth factor (VEGF) and bFGF and decreased the expression of GAP43 in the cortex of MCAO rats. CGRP promoted cell proliferation and cell cycle process and inhibited cell apoptosis through the Wnt/β-catenin pathway in NHA cells. CONCLUSIONS This noninvasive, simple, and cost-effective method is a potential treatment strategy for focal cerebral ischemic injury. |
| Databáze: | OpenAIRE |
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