Persistent inflammation alters the function of the endogenous brain stem cell compartment.
Persistent inflammation alters the function of the endogenous brain stem cell compartment.
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DOI：
10.1093/brain/awn198
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Martino G
中科院分区：
文献类型：
--
作者：
Pluchino S;Muzio L;Imitola J;Deleidi M;Alfaro-Cervello C;Salani G;Porcheri C;Brambilla E;Cavasinni F;Bergamaschi A;Garcia-Verdugo JM;Comi G;Khoury SJ;Martino G
内源性神经干/前体细胞（NPC）被认为是促进组织稳态和损伤后修复的功能性储库，因此最近提出了动员这些细胞的再生策略。尽管有证据表明急性炎性损伤（如缺血性卒中）后神经发生增加，但慢性CNS炎性疾病中内源性脑干细胞区室的可塑性仍然很差。在这里，我们表明，持续性的脑炎症，诱导免疫细胞靶向髓鞘，广泛地改变了增殖和迁移特性的室管膜下区（SVZ）的居民NPC在体内导致显着积累的非迁移性神经母细胞内的SVZ germinal生态位。同时，我们证明了在持续性脑炎症过程中SVZ中推定的脑干细胞增殖的定量减少，这在分离的NPC体外培养后完全逆转。总之，这些数据表明，发炎的脑微环境维持内源性CNS干细胞区室的非细胞自主功能障碍，并挑战了旨在动员慢性炎症性脑疾病中的内源性前体的拟议疗法的潜在疗效。
Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain inflammation, induced by immune cells targeting myelin, extensively alters the proliferative and migratory properties of subventricular zone (SVZ)-resident NPCs in vivo leading to significant accumulation of non-migratory neuroblasts within the SVZ germinal niche. In parallel, we demonstrate a quantitative reduction of the putative brain stem cells proliferation in the SVZ during persistent brain inflammation, which is completely reversed after in vitro culture of the isolated NPCs. Together, these data indicate that the inflamed brain microenvironment sustains a non cell-autonomous dysfunction of the endogenous CNS stem cell compartment and challenge the potential efficacy of proposed therapies aimed at mobilizing endogenous precursors in chronic inflammatory brain disorders.
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影响因子：
3.7
作者：
Muzio, L;Soria, JM;Mallamaci, A
通讯作者：
Mallamaci, A
影响因子：
5.3
作者：
Bull, ND;Bartlett, PF
通讯作者：
Bartlett, PF
DOI：
10.1073/pnas.0603512103
发表时间：
2006-08-29
影响因子：
11.1
作者：
Jin, Kunlin;Wang, Xiaomei;Greenberg, David A.
通讯作者：
Greenberg, David A.
DOI：
10.1073/pnas.192314199
发表时间：
2002-10-01
影响因子：
11.1
作者：
Picard-Riera, N;Decker, L;Baron-Van Evercooren, A
通讯作者：
Baron-Van Evercooren, A
影响因子：
16.2
作者：
MORSHEAD, CM;REYNOLDS, BA;VANDERKOOY, D
通讯作者：
VANDERKOOY, D