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首页> 外文期刊>Neuropathology and applied neurobiology >Intracisternal enzyme replacement therapy in lysosomal storage diseases: Dispersal pathways, regional enzyme concentrations and the effect of posttreatment posture
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Intracisternal enzyme replacement therapy in lysosomal storage diseases: Dispersal pathways, regional enzyme concentrations and the effect of posttreatment posture

机译：溶酶体贮积病的脑内酶替代疗法：弥散途径，区域酶浓度和治疗后姿势的影响

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Aims: To investigate routes of dispersal of enzyme, its regional uptake and the effect of posture when replacement enzyme is administered directly into the cerebrospinal fluid (CSF). Methods: Dispersal pathways of particles and solutes were investigated using intracisternal injections of india ink with visual assessment, and a contrast medium (Iohexol) with computer tomography (CT). Replacement enzyme was measured at 46 loci within the central nervous system (CNS) in four groups of dogs subjected to different post-injection postural changes. Results: India ink and CT studies showed dispersal pathways for CSF to be mainly via cisterns and sulci. Replacement enzyme reached all areas of the CNS tested, although mean concentrations varied 49-fold over different areas of the brain. Posttreatment posture had only modest effects on enzyme uptake in limited anatomical sites. Conclusions: Dispersal of solutes after injection is rapid and initially enhanced by the injection process. Preferential pathways for CSF flow in the subarachnoid spaces of the brain involve cisterns and sulci. The splenial and suprasplenial sulci in particular appear important conduits for dispersal to more dorsal and rostral areas of the brain. Expansion and contraction of these sulci during brain pulsation is considered important to the forward flow of solutes in CSF through these compartments. Following intracisternal enzyme replacement therapy, enzyme reached all areas of the brain, but there was considerable disparity of enzyme uptake with some areas recording much higher levels than others. Posttreatment posture made only modest differences to enzyme uptake.
机译：目的：研究将替代酶直接注入脑脊液（CSF）后酶的扩散途径，其区域吸收和姿势的影响。方法：采用视觉评估通过印度脑池脑内注射，计算机断层扫描（CT）造影剂（Iohexol）研究颗粒和溶质的扩散途径。在四组遭受不同注射后姿势变化的狗中，在中枢神经系统（CNS）的46个基因座上测定了替代酶。结果：印度墨水和CT研究表明，脑脊液的扩散途径主要是通过水箱和渠道。替代酶到达了受测中枢神经系统的所有区域，尽管平均浓度在大脑的不同区域变化了49倍。后处理姿势在有限的解剖部位仅对酶的吸收有中等程度的影响。结论：注射后溶质的扩散迅速，并且最初在注入过程中得到增强。脑脊液蛛网膜下腔中脑脊液流动的优先途径涉及储水池和沟。脾脏和脾上神经尤其出现在弥散到大脑的背侧和延侧区域的重要管道。这些脉动在脑部搏动期间的扩张和收缩被认为对于溶质在脑脊液中通过这些隔室的正向流动很重要。进行脑池内酶替代治疗后，酶到达了大脑的所有区域，但是酶的吸收差异很大，某些区域的水平要高得多。处理后的姿势对酶的吸收仅产生适度的差异。

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