室下区
纽恩
神经发生
缺血
溴脱氧尿苷
神经干细胞
双皮质醇
纹状体
齿状回
神经保护
神经科学
海马体
医学
内分泌学
生物
内科学
细胞生物学
干细胞
多巴胺
免疫组织化学
作者
Yingxun Liu,Junrong Ren,Mengsi Kang,Chenyang Zhai,Qiangqiang Cheng,Li Jin,Yuzi Wu,Xiaofei Ruan,Jinlong Zhou,Juan Fan,Yingfang Tian
出处
期刊:Brain Research
[Elsevier]
日期:2021-04-01
卷期号:1757: 147312-147312
被引量:8
标识
DOI:10.1016/j.brainres.2021.147312
摘要
Progranulin (PGRN), a secreted glycosylated protein, has been reported to attenuate ischemia-induced cerebral injury through anti-inflammation, attenuation of blood-brain barrier disruption and neuroprotection. However, the effect of PGRN on neurogenesis in the subventricular zone (SVZ) after cerebral ischemia remains unclear. In this study, adult C57BL/6 mice were subjected to permanent middle cerebral artery occlusion (pMCAO), and different doses of recombinant mouse PGRN (r-PGRN, 0.3 ng, 1 ng, 5 ng) were intracerebroventricularly administered 30 min after pMCAO. Results showed that 1 ng r-PGRN markedly reduced infarct volume and rescued functional deficits 24 h after pMCAO. Meanwhile, 1 ng r-PGRN increased SVZ cell proliferation, as shown by a high number of bromodeoxyuridine-positive (BrdU+) cells and Ki-67+ cells in the ischemic ipsilateral SVZ 7 d after pMCAO. Additionally, PGRN increased the percentage of BrdU+/Doublecortin (DCX)+ cells in the ipsilateral SVZ 14 d after pMCAO and increased the percentage of new neurons (BrdU+/NeuN+ cells) in the peri-infarct striatum 28 d after pMCAO, suggesting that PGRN promotes neuronal differentiation. PGRN also upregulated phosphorylation of ERK1/2 and Akt in the ipsilateral SVZ 3 d after pMCAO. Our data indicate that PGRN treatment promotes acute functional recovery; most importantly, it also stimulates neurogenesis in the SVZ, which could be beneficial for long-term recovery after cerebral ischemia. The increase in neurogenesis could be associated with activation of the MAPK/ERK and PI3K/Akt pathways. These results suggest a potential new strategy utilizing PGRN in ischemic stroke therapy.
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