Dynamic induction of the myelin-associated growth inhibitor Nogo-A in perilesional plasticity regions after human spinal cord injury.
Dynamic induction of the myelin-associated growth inhibitor Nogo-A in perilesional plasticity regions after human spinal cord injury.
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DOI：
10.1111/bpa.13098
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发表时间：
2023-01
期刊：
影响因子：
6.4
通讯作者：
Hoeftberger, Romana
中科院分区：
文献类型：
--
作者：
Schwaiger, Carmen;Haider, Thomas;Endmayr, Verena;Zrzavy, Tobias;Gruber, Victoria E.;Ricken, Gerda;Simonovska, Anika;Hametner, Simon;Schwab, Jan M.;Hoeftberger, Romana
髓磷脂相关抑制剂 Nogo-A（Reticulon 4，RTN4）可限制脊髓损伤 (SCI) 实验模型中的轴突生长、可塑性和神经回路形成，并且是 SCI 后 4 周内开始治疗的临床干预的目标。具体来说，少突胶质细胞表达的 Nogo-A 限制代偿性神经突萌芽。为了质疑随时间推移诱导性病变反应性 Nogo-A 表达的假设，我们分析了脊髓病变核心（组织坏死和轴突损伤/修剪区域）和病变周围边缘（可塑性形成区域）的时空 Nogo-A 表达。将 SCI 受试者 (n = 22) 的脊髓标本与神经病理学未改变的对照 (n = 9) 进行比较。对Nogo-A表达的研究范围包括SCI后的急性（0-3天）、早期亚急性（4-21天）、晚期亚急性（22-90天）到早期慢性-慢性（SCI后91天至1.5年）阶段。对照组中的 Nogo-A 表达仅限于前角的运动神经元以及灰质和白质的少突胶质细胞。 SCI 后，Nogo-A+ 和 TPPP/p25+ 少突胶质细胞的数量 (i) 特别倾向于组织性病变周围边缘，(ii) 随着时间的推移进一步增加，(iii) 在 SCI 后的慢性阶段达到峰值。相比之下，在病变核心，Nogo-A+ 和 TPPP/p25+ 少突胶质细胞的数量没有增加。 Nogo-A+ 少突胶质细胞数量的增加与少突胶质细胞发生同时发生，Ki67+、TPPP/p25+ 增殖少突胶质细胞的 Nogo-A 共表达证实了这一点。随着时间的推移，Nogo-A 少突胶质细胞表达出现在病灶周围（可塑性）区域，这表明针对 SCI 后患者 4 周以上的干预，抗 Nogo-A 途径的治疗窗更长。随着时间的推移，Nogo-A 少突胶质细胞表达出现在病灶周围区域，这表明脊髓损伤后患者的抗 Nogo-A 通路靶向干预治疗窗延长至超过 4 周。
The myelin‐associated inhibitor Nogo‐A (Reticulon 4, RTN4) restricts axonal outgrowth, plasticity, and neural circuitry formation in experimental models of spinal cord injury (SCI) and is targeted in clinical interventions starting treatment within 4 weeks post‐SCI. Specifically, Nogo‐A expressed by oligodendroglia restricts compensatory neurite sprouting. To interrogate the hypothesis of an inducible, lesion reactive Nogo‐A expression over time, we analyzed the spatiotemporal Nogo‐A expression at the spinal lesion core (region of tissue necrosis and axonal damage/pruning) and perilesional rim (region of plasticity formation). Spinal cord specimens of SCI subjects (n = 22) were compared to neuropathologically unaltered controls (n = 9). Nogo‐A expression was investigated ranging from acute (0–3 days), early subacute (4–21 days), late subacute (22–90 days) to early chronic–chronic (91 days to 1.5 years after SCI) stages after SCI. Nogo‐A expression in controls is confined to motoneurons in the anterior horn and to oligodendrocytes in gray and white matter. After SCI, the number of Nogo‐A+ and TPPP/p25+ oligodendrocytes (i) inclined at the organizing perilesional rim specifically, (ii) increased further over time, and (iii) peaked at chronic stages after SCI. By contrast, at the lesion core, the number of Nogo‐A+ and TPPP/p25+ oligodendrocytes did not increase. Increasing numbers of Nogo‐A+ oligodendrocytes coincided with oligodendrogenesis corroborated by Nogo‐A coexpression of Ki67+, TPPP/p25+ proliferating oligodendrocytes. Nogo‐A oligodendrocyte expression emerges at perilesional (plasticity) regions over time and suggests an extended therapeutical window for anti‐Nogo‐A pathway targeting interventions beyond 4 weeks in patients after SCI. Nogo‐A oligodendrocytes expression emerges at perilesional regions over time and suggests an extended therapeutical window for anti‐Nogo‐A pathway trageting interventrions beyond four weeks in patients after spinal cord injury.
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抗Nogo-A抗体治疗促进成年灵长类单侧颈椎损伤后手灵巧度的恢复——行为数据的重新检查和扩展。
DOI：
10.1111/j.1460-9568.2009.06642.x
发表时间：
2009-03
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Freund P;Schmidlin E;Wannier T;Bloch J;Mir A;Schwab ME;Rouiller EM
通讯作者：
Rouiller EM
影响因子：
14.5
作者：
Fleming, Jennifer C.;Norenberg, Michael D.;Weaver, Lynne C.
通讯作者：
Weaver, Lynne C.
影响因子：
2.2
作者：
Fawcett, J. W.;Curt, A.;Short, D.
通讯作者：
Short, D.
影响因子：
64.8
作者：
Chen, MS;Huber, AB;Schwab, ME
通讯作者：
Schwab, ME
影响因子：
6.2
作者：
Hoeftberger, Romana;Fink, Stephanie;Kovacs, Gabor G.
通讯作者：
Kovacs, Gabor G.