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Neurosci Lett. 2018 Nov 20;687:94-98. doi: 10.1016/j.neulet.2018.09.035. Epub 2018 Sep 22.

Miconazole stimulates post-ischemic neurogenesis and promotes functional restoration in rats.

Author information

1
Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, 510632, China.
2
Department of Rehahilitation, the First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
3
Key Laboratory of Modern Toxicology of Shenzhen, Center for Disease Control and Prevention, No. 8, Longyuan Road, Nanshan District, Shenzhen 518055, China.
4
Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, 510632, China. Electronic address: zhanggaoxiao2005@163.com.
5
Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, 510632, China. Electronic address: zaijunzhang@163.com.

Abstract

Miconazole, a frequently used antifungal drug, has been identified with new functions to promote oligodendrocyte progenitor cells differentiation and to enhance remyelination. However, the neuroregenerative and therapeutic benefit of miconazole on ischemic stroke model have not been tested. In the present study, the effects of miconazole on a rat model of transient middle cerebral artery occlusion were evaluated. Rats received miconazole (10 mg/kg) or saline by intravenous administration for 7 days after stroke. A battery of neurobehavioral assessments, including rotarod test, open-field test, neurological severity score and novel object recognition task were evaluated. The results revealed a significant functional improvement in miconazole-treated rats compared with vehicle-treated control. Animals were sacrificed at 7 and 28 days after stroke. Double immunofluorescence staining for NeuN+/BrdU+, DCX+/BrdU+ and Nestin+/BrdU+ cells indicated miconazole significantly promoted neurogenesis. Western blotting analysis revealed miconazole upregulated the protein expression of brain derived neurotrophic factor, myocyte enhancer factor 2D, synaptophysin, and postsynaptic density protein 95, while downregulated the expression of cyclin-dependent kinase 5. Taken together, miconazole promoted functional recovery on ischemic stroke model via stimulating post-ischemic neurogenesis.

KEYWORDS:

Brain derived neurotrophic factor; Ischemic stroke; Miconazole; Neuroregeneration

PMID:
30253223
DOI:
10.1016/j.neulet.2018.09.035
[Indexed for MEDLINE]

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