Treatment with the PPARγ Agonist Pioglitazone in the Early Post-ischemia Phase Inhibits Pro-inflammatory Responses and Promotes Neurogenesis Via the Activation of Innate- and Bone Marrow-Derived Stem Cells in Rats.
Treatment with the PPARγ Agonist Pioglitazone in the Early Post-ischemia Phase Inhibits Pro-inflammatory Responses and Promotes Neurogenesis Via the Activation of Innate- and Bone Marrow-Derived Stem Cells in Rats.
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DOI：
10.1007/s12975-017-0577-8
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发表时间：
2018-06
影响因子：
6.9
通讯作者：
Nagahiro S
中科院分区：
文献类型：
--
作者：
Kinouchi T;Kitazato KT;Shimada K;Yagi K;Tada Y;Matsushita N;Kurashiki Y;Satomi J;Sata M;Nagahiro S
神经发生对于良好的卒中后结局至关重要。目前正在测试外源性干细胞促进中风后神经发生。在其他地方，我们证明了在脑缺血诱导前用PPARγ激动剂吡格列酮（PGZ）治疗可以减少卵巢切除（OVX）大鼠的脑损伤并激活生存相关基因。在这里，我们测试了我们的假设，即缺血后用PGZ治疗抑制脑损伤，并通过激活干细胞促进神经发生。用来自绿色荧光蛋白转基因（GFP+BM）大鼠的BM细胞替换7周龄Wistar雌性大鼠的骨髓（BM）细胞。三周后，切除卵巢（OVX/GFP+BM大鼠）。我们对7周龄Wistar雄性和13周龄OVX/GFP+BM大鼠进行90分钟脑缺血。将雄性和OVX/GFP+BM大鼠分为两组，一组给予PGZ（2.5 mg/kg/天），另一组作为溶剂对照（VC）。在雄性和OVX/GFP+BM大鼠中，缺血后用PGZ治疗减少了神经功能缺损和梗死体积。在雄性大鼠中，PGZ在24 h后降低IL-6和M1样巨噬细胞的mRNA水平。在OVX/GFP+BM大鼠中，PGZ在第7-14天增强了室管膜下区（SVZ）中驻留干细胞的增殖和GFP+BM干细胞的募集。两种类型的增殖干细胞都从SVZ迁移到梗死周围区域。在那里，它们分化成与激活的Akt、MAP 2和VEGF相关的成熟神经元、胶质细胞和血管。缺血后用PGZ治疗可能通过促进神经保护和神经发生为中风治疗提供新途径。
Neurogenesis is essential for a good post-stroke outcome. Exogenous stem cells are currently being tested to promote neurogenesis after stroke. Elsewhere, we demonstrated that treatment with the PPARγ agonist pioglitazone (PGZ) before cerebral ischemia induction reduced brain damage and activated survival-related genes in ovariectomized (OVX) rats. Here, we tested our hypothesis that post-ischemia treatment with PGZ inhibits brain damage and contributes to neurogenesis via activated stem cells. Bone marrow (BM) cells of 7-week-old Wistar female rats were replaced with BM cells from green fluorescent protein-transgenic (GFP+BM) rats. Three weeks later, they were ovariectomized (OVX/GFP+BM rats). We subjected 7-week-old Wistar male and 13-week-old OVX/GFP+BM rats to 90-min cerebral ischemia. Male and OVX/GFP+BM rats were divided into two groups, one was treated with PGZ (2.5 mg/kg/day) and the other served as the vehicle control (VC). In both male and OVX/GFP+BM rats, post-ischemia treatment with PGZ reduced neurological deficits and the infarct volume. In male rats, PGZ decreased the mRNA level of IL-6 and M1-like macrophages after 24 h. In OVX/GFP+BM rats, PGZ augmented the proliferation of resident stem cells in the subventricular zone (SVZ) and the recruitment of GFP+BM stem cells on days 7–14. Both types of proliferated stem cells migrated from the SVZ into the peri-infarct area. There, they differentiated into mature neurons, glia, and blood vessels in association with activated Akt, MAP2, and VEGF. Post-ischemia treatment with PGZ may offer a new avenue for stroke treatment through contribution to neuroprotection and neurogenesis.
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DOI：
10.1161/01.atv.0000143096.15099.ce
发表时间：
2004-10-01
影响因子：
8.7
作者：
Schabbauer, G;Tencati, M;Mackman, N
通讯作者：
Mackman, N
影响因子：
9.3
作者：
Biscetti F;Straface G;Arena V;Stigliano E;Pecorini G;Rizzo P;De Angelis G;Iuliano L;Ghirlanda G;Flex A
通讯作者：
Flex A
影响因子：
3.4
作者：
Patzer, Andreas;Zhao, Yi;Culman, Juraj
通讯作者：
Culman, Juraj
人骨髓间充质干细胞移植促进脑缺血大鼠行为恢复和内源性神经发生
影响因子：
2.9
作者：
Bao, Xinjie;Wei, Junji;Wang, Renzhi
通讯作者：
Wang, Renzhi
影响因子：
8.3
作者：
Kinouchi, Tomoya;Kitazato, Keiko T.;Nagahiro, Shinji
通讯作者：
Nagahiro, Shinji