Effects of RO27-3225 on neurogenesis, PDGFRβ+ cells and neuroinflammation after cerebral infarction
Effects of RO27-3225 on neurogenesis, PDGFRβ+ cells and neuroinflammation after cerebral infarction
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RO27-3225 对脑梗死后神经发生、PDGFRβ 细胞和神经炎症的影响
DOI：
10.1016/j.intimp.2020.106281
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发表时间：
2020-04-01
影响因子：
5.6
通讯作者：
Man, Jiang
中科院分区：
文献类型：
--
作者：
Zhang, Yongxin;Wang, Jianping;Man, Jiang
Cerebral infarction causes severe social and economic burdens to patients due to its high morbidity and mortality rates, and the available treatments are limited. RO27-3225 is a highly selective melanocortin receptor 4 agonist that alleviates damage in many nervous system diseases, such as cerebral hemorrhage, traumatic brain injury and chronic neurodegenerative diseases. However, the effect of RO27-3225 on cerebral infarction remains unclear. In this study, we used a mouse model of transient middle cerebral artery occlusion (tMCAO) and administered RO27-3225 or saline to the mice through intraperitoneal injection. RO27-3225 increased the number of Nestin(+)/BrdU(+) cells and doublecortin (DCX)(+)/BrdU(+) cells in the subventricular zone (SVZ) and the number of DCX+/BrdU(+) cells in the peri-infarct area on day 7 after tMCAO. Furthermore, RO27-3225 decreased the number of activated microglia (Iba1(+) cells with a specific morphology) and the expression levels of Iba1, TNF alpha, IL6, and iNOS proteins and increased the number of PDGFR beta(+) cells in the peri-infarct region on day 3 after tMCAO. Finally, RO27-3225-treated mice exhibited significantly decreased infarct volumes, brain water contents, and neurological deficits after cerebral infarction. Thus, RO27-3225 can improve the outcomes following cerebral infarction, partially by regulating neurogenesis in the SVZ, PDGFR beta(+) cell survival and neuroinflammation in the peri-infarct zone. Our research reveals that RO27-3225 is a potential new treatment for cerebral infarction.
