Perlecan Domain-V Enhances Neurogenic Brain Repair After Stroke in Mice.
Perlecan Domain-V Enhances Neurogenic Brain Repair After Stroke in Mice.
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Perlecan结构域-V促进小鼠中风后的神经源性脑修复。
DOI：
10.1007/s12975-020-00800-5
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发表时间：
2021-03
影响因子：
6.9
通讯作者：
Bix GJ
中科院分区：
文献类型：
--
作者：
Trout AL;Kahle MP;Roberts JM;Marcelo A;de Hoog L;Boychuk JA;Grupke SL;Berretta A;Gowing EK;Boychuk CR;Gorman AA;Edwards DN;Rutkai I;Biose IJ;Ishibashi-Ueda H;Ihara M;Smith BN;Clarkson AN;Bix GJ
细胞外基质片段基底膜蛋白聚糖结构域 V 在实验性中风后具有神经保护和功能恢复作用。由于神经发生是慢性中风后修复的重要组成部分，并且之前的研究表明基底膜蛋白聚糖参与发育性神经发生，因此我们假设结构域 V 可以通过增强中风后神经发生而具有广阔的治疗窗口。我们证明，人类中风患者大脑中的 V 区长期增加，表明它存在于中风后神经源性时期。此外，基底膜蛋白缺陷小鼠在实验性中风后其神经母细胞前体细胞显着减少。实验性中风后，延迟 7 天的 V 域给药增强了神经发生，并恢复了梗塞周围新皮质层 2/3 锥体神经元的兴奋性突触驱动。 α2β1 整合素的阻断可抑制 V 区的作用，这表明 α2β1 整合素对神经发生和 V 区神经原性作用的重要性。我们的结果表明基底膜蛋白聚糖在中风后神经发生中发挥着以前未被认识到的作用，并且实验性中风后延迟 DV 给药可增强神经发生并以 α2β1 整合素介导的方式改善恢复。我们得出的结论是，V 域是一种临床相关的神经保护和神经修复新型中风疗法，具有广泛的治疗窗口。本文的在线版本 (10.1007/s12975-020-00800-5) 包含补充材料，可供授权用户使用。
The extracellular matrix fragment perlecan domain V is neuroprotective and functionally restorative following experimental stroke. As neurogenesis is an important component of chronic post-stroke repair, and previous studies have implicated perlecan in developmental neurogenesis, we hypothesized that domain V could have a broad therapeutic window by enhancing neurogenesis after stroke. We demonstrated that domain V is chronically increased in the brains of human stroke patients, suggesting that it is present during post-stroke neurogenic periods. Furthermore, perlecan deficient mice had significantly less neuroblast precursor cells after experimental stroke. Seven-day delayed domain V administration enhanced neurogenesis and restored peri-infarct excitatory synaptic drive to neocortical layer 2/3 pyramidal neurons after experimental stroke. Domain V’s effects were inhibited by blockade of α2β1 integrin, suggesting the importance of α2β1 integrin to neurogenesis and domain V neurogenic effects. Our results demonstrate that perlecan plays a previously unrecognized role in post-stroke neurogenesis and that delayed DV administration after experimental stroke enhances neurogenesis and improves recovery in an α2β1 integrin-mediated fashion. We conclude that domain V is a clinically relevant neuroprotective and neuroreparative novel stroke therapy with a broad therapeutic window. The online version of this article (10.1007/s12975-020-00800-5) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Gustafsson E;Almonte-Becerril M;Bloch W;Costell M
通讯作者：
Costell M
影响因子：
6.9
作者：
Bix, Gregory J.;Gowing, Emma K.;Clarkson, Andrew N.
通讯作者：
Clarkson, Andrew N.
影响因子：
10.4
作者：
Moors M;Rockel TD;Abel J;Cline JE;Gassmann K;Schreiber T;Schuwald J;Weinmann N;Fritsche E
通讯作者：
Fritsche E
影响因子：
1.2
作者：
Kerever, Aurelien;Mercier, Frederic;Nonaka, Risa;de Vega, Susana;Oda, Yuka;Zalc, Bernard;Okada, Yohei;Hattori, Nobutaka;Yamada, Yoshihiko;Arikawa-Hirasawa, Eri
通讯作者：
Arikawa-Hirasawa, Eri
影响因子：
--
作者：
Giros, Amparo;Morante, Javier;Costell, Mercedes
通讯作者：
Costell, Mercedes