Quantitative analysis by in vivo imaging of the dynamics of vascular and axonal networks in injured mouse spinal cord

Quantitative analysis by in vivo imaging of the dynamics of vascular and axonal networks in injured mouse spinal cord
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DOI:
10.1073/pnas.0900222106
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发表时间:
2009-06-09
影响因子:
11.1
通讯作者:
Debarbieux, Franck
Debarbieux, Franck
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Dray, Cyril;Rougon, Genevieve;Debarbieux, Franck

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了解脊髓的内源性修复能力是制定改善策略的关键,在此,我们设计了一个脊髓损伤的范例,使用双光子显微镜技术,动态和长期监测的血管和轴突网络的同时变化在活体小鼠脊髓损伤后4个月。高分辨率图像显示,早期探索发芽幸存的损伤轴突导致广泛的再生,直到和过去的病变部位在2个月内。血管密度短暂上调,大多数神经血管相互作用发生在2周内。时间推移分析表明,新生血管产生了一个强大的生长刺激作用,但没有指导作用,相邻的芽,可能是因为他们的几何形状和可塑性。然而,如果重新连接依赖于轴突芽密度,则刺激血管生成可能有利于修复。更一般地说,这种成像方法显示出有助于监测脑部疾病和潜在治疗效果的希望。
Understanding the endogenous repair capacity of spinal cord is pivotal to develop strategies to improve it. Here we design a paradigm of spinal cord lesion in the dorsal column using a 2-photon microscopy technique to dynamically and chronically monitor simultaneous changes of vascular and axonal networks in living mice up to 4 months postinjury. High-resolution images showed that early explorative sprouting of surviving injured axons resulted in extensive regrowth until and past the lesion site within 2 months. Blood vessel density was transiently up-regulated and most neurovascular interactions occurred within 2 weeks. Time-lapse analysis showed that neovessels exerted a potent growth stimulating action, but no guidance effect on neighboring sprouts, possibly because of their geometry and plasticity. Nevertheless, if reconnection depends on axon sprout density, stimulation of angiogenesis would probably be beneficial to repair. More generally, this imaging approach is showing promise to aid in monitoring brain diseases and the efficacy of potential treatments.