中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (11): 2209-2210.doi: 10.4103/1673-5374.310681

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

脑卒中后无创分子影像学方法评估神经胶质细胞的增殖

  

  • 出版日期:2021-11-15 发布日期:2021-04-13

Evaluation of glial cell proliferation with non-invasive molecular imaging methods after stroke

Ana Joya, Abraham Martín   

  1. Achucarro Basque Center for Neuroscience, Leioa, Spain (Joya A, Martín A)
    CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), Paseo, Spain (Joya A)
    Ikerbasque Basque Foundation for Science, Bilbao, Spain (Martín A)
  • Online:2021-11-15 Published:2021-04-13
  • Contact: Abraham Martín, PhD, abraham.martin@achucarro.org.
  • Supported by:
    This work was supported by grants from the Spanish Ministry of Education and Science (RYC-2017-22412, PID2019-107989RB-I00 and MDM-2017-0720), the Basque Government (BIO18/IC/006) and Fundació La Marató de TV3 (17/C/2017). 

摘要:

Neural Regen Res:分子成像方法评价体内胶质细胞增殖

    在过去的几十年中,人们错误地认为神经胶质细胞仅对神经元起被动的支持作用,然而这种观念已经发生了明显的变化,现在人们认识到这些细胞对于神经系统的正常发育和调节至关重要。神经胶质细胞可以进行分化增殖,并且修复受伤组织,推断出成年哺乳动物大脑神经炎症后具有组织修复的能力。由此引出了一系列再生胶质细胞作为诊断和治疗脑部疾病的治疗靶点的有用性及其在临床适用性的相关问题。因此,发展分子成像方法来评价胶质细胞在体内的增殖仍有必要。

来自西班牙阿卡卡罗巴斯克神经科学中心的Abraham Martín团队最近研究发现在脑缺血后1周,[18F] FLT摄取增加,然后2-4周下降,并且下降趋势与TSPO放射性配体相似。因此,PET成像数据支持在实验性中风后活化和增殖性神经胶质细胞都遵循相似的时间模式。PET成像使用[18F]FLT已被证明是一种更容易获得的方法,并有可能应用于临床。尽管如此,[18F]FLT仍有一定的局限性,如(i)区分增殖细胞类型的能力;(ii) PET成像的细胞分辨率低;(iii)研究大脑时血脑屏障的限制。而且,通过这种成像方法观察到的神经胶质增生仍然需要通过离体免疫组织化学研究来验证,从而限制了其在预临床研究领域的应用。另外,磁共振成像方法可能提供比核成像更高的分辨率,具有强大的平移潜力。磁共振成像报告基因和超顺磁氧化铁颗粒标记增殖细胞正在被测试来研究体内神经发生和胶质发生。尽管每种分子成像方式都有其优势和局限性,在过去的几十年里,这一领域依然取得了长足的进步,缩小了预临床研究和临床研究之间的差距。

 

文章在《中国神经再生研究(英文版)》杂志20211111期发表。

https://orcid.org/0000-0002-5357-4935 (Abraham Martín)

Abstract: Glial proliferation: For the last decades, glial cells have been wrongly believed to have a mere passive supporting role for neurons. Nevertheless, this notion has clearly changed and it is now admitted that these cells are essential for the correct development and regulation of the nervous system. Glia cell population are commonly subdivided in astrocytes, oligodendrocytes and microglia. During the development, neural stem cells (NSCs) (called neuroepithelial progenitor cells or NPCs) transform into radial glia, the primary progenitor cells for neurons, astrocytes and oligodendrocytes (Zuchero and Barres, 2015). Microglial cells, however, derive from a mesenchymal precursor infiltration, meaning that during brain development, precursors generated in the bone narrow invade the nervous parenchyma and differentiate into microglial cells (Zuchero and Barres, 2015). This proliferative capacity is preserved in the adult mammalian brain, and neurogenic NSCs are stored in two restricted regions of the central nervous system (CNS), the forebrain subventricular zone (SVZ) and the hippocampal dentate gyrus (subgranular zone). These cells continue to produce neurons and glial cells during the adulthood, being activated after certain signals and leaving the quiescent state (Urbán et al., 2019). This process, in which glial progenitor cells differentiate into mature glia during development and in the adult brain to maintain and regulate brain function, is called gliogenesis (Ardaya et al., 2020). Besides these two niches, oligodendrocyte progenitor cells (OPCs) are present all around the CNS, both in the white and gray matter. These cells are the major dividing cells in the CNS generating new myelinating oligodendrocytes, or to a lesser extent astrocytes and they are constantly scanning the environment and controlling brain homeostasis. In addition, there is evidence of generation of new astrocytes from proliferating mature astrocytes in the brain parenchyma (Frisén, 2016). In summary, the capacity of generation of new glial cells is preserved not only in the SVZ and subgranular zone niches, but in the parenchymal tissue of the adult brain. In fact, the proliferative capacity of glial cells is increased in the injured CNS following neurological diseases. Adult OPCs play an important role in demyelinating diseases, where they turn to an activated state and start proliferating and migrating to the demyelination areas. Once there, they differentiate into mature oligodendrocytes and renew the destroyed myelin (Kuhn et al., 2019). After brain ischemia, microglia and astrocytes play an important role, representing the primary defense line facing neuroinflammation. Different studies using rodents have tried to disclose how microglia and astrocytes behave in this context and what triggers its activation. There is evidence of formation of a glial scar by reactive astrocytes originated from NSCs in the SVZ niche, but also generated through proliferation of local resident astrocytes (Nakafuku and Del Águila, 2020). Krishnasamy et al. (2017) showed the expression of nestin, a stem cell marker, in both reactive astrocytes and activated microglia after brain injury. These studies confirmed that glial cells differentiate and proliferate in order to restore the injured tissue, concluding that adult mammalian brain has the capacity of tissue repair following neuroinflammation.