Two-photon fluorescent imaging of myelination in the spinal cord.

Two-photon fluorescent imaging of myelination in the spinal cord.
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脊髓髓鞘形成的双光子荧光成像。

DOI:
10.1002/cmdc.201200343
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发表时间:
2012
期刊:
影响因子:
3.4
通讯作者:
Wang,Yanming
Wang,Yanming
中科院分区:
医学4区
文献类型:
--
作者:
Condie,AllisonG;Gerson,StantonL;Miller,RobertH;Wang,Yanming

文献摘要

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髓鞘形成是脊椎动物神经系统中的基本生物学过程。髓鞘的损伤或畸形可导致各种神经系统疾病;例如,脊髓中的脱髓鞘是患有多发性硬化症和相关疾病的患者瘫痪的主要原因。为了评估治疗剂在促进髓鞘修复中的功效,需要直接追踪脊髓中髓鞘水平的能力。为了解决这一未满足的需求,4-((E)-4-((E)-4-氨基苯乙烯基)-2,5-二甲氧基苯乙烯基)-N-甲基苯胺,称为Case Imaging Compound(CIC),已被开发为选择性结合髓磷脂的髓磷脂靶向荧光成像剂。通过改进的途径合成CIC,并在脱髓鞘和髓鞘发育障碍模型中作为脊髓中髓鞘的双光子荧光成像的荧光探针进行评价。 体外和离体组织染色均表明CIC在动物模型中选择性结合。 在动物模型中的进一步评估表明,CIC对健康与病理髓鞘中髓鞘含量的差异敏感。CIC可能在多发性硬化和其他脱髓鞘疾病的新疗法的开发和评估中有潜在的用途。
Myelination is a fundamental biological process in the vertebrate nervous system. Damage to or malformation of myelin can lead to various neurological diseases; for example, demyelination in the spinal cord is a major cause of paralysis of patients suffering from multiple sclerosis and related diseases. The ability to directly track myelin levels in the spinal cord is needed in order to assess the efficacy of therapeutics in promoting myelin repair. To address this unmet need, 4‐((E)‐4‐((E)‐4‐aminostyryl)‐2,5‐dimethoxystyryl)‐N‐methylaniline, known as Case Imaging Compound (CIC), has been developed as a myelin‐targeted fluorescent imaging agent that selectively binds to myelin. CIC was synthesized via an improved route and evaluated as a fluorescent probe for two‐photon fluorescent imaging of myelin in the spinal cord in both demyelinated and dysmyelinated models. In vitro and ex vivo tissue staining both suggest that CIC selectively binds to in animal models. Further evaluation in animal models indicated that CIC is sensitive to differences in myelin content in healthy versus pathological myelin. CIC could potentially be useful in the development and evaluation of novel therapies for multiple sclerosis and other demyelinating diseases.