Department of Anatomy, University of Ibadan, Nigeria.
Department of Anatomy, University of Ibadan, Nigeria; Department of Surgery, University of Ibadan, Nigeria.
Neuroscience. 2019 Nov 1;419:14-22. doi: 10.1016/j.neuroscience.2019.08.049. Epub 2019 Sep 3.
Hydrocephalus is especially prevalent in countries with limited resources, where its treatment is still a challenge. However, long-term neuropathological changes in untreated hydrocephalus remain largely unexplored. The present study looks at cortical parenchyma and neuroinflammation in acquired, chronic hydrocephalus. Intracisternal kaolin injections were performed in 3-week-old rats, followed by -1, 4- and 8-week survival; matched control rats received saline injections. Ventriculomegaly has been previously reported to stabilize by the third week in this model. Single and triple immunocytochemical approaches were used to highlight neurones, astrocytes, microglia, and the pro-inflammatory cytokine interleukin (IL)-1β in the parietal cortex, utilizing cell counts and densitometry. Microglial protein ionized calcium binding adaptor molecule 1 (Iba1) and IL-1β expressions were monitored with Western blotting in the parietal cortex and hippocampus. In the parietal cortex, which showed progressive disruption of cytoarchitecture, neuronal density was significantly increased at 8weeks post-induction but not at earlier time points, indicating on-going cortical damage in chronic hydrocephalus. Astrocyte and microglia hypertrophy, and Iba1 expression indicated glial cell activation which peaked at 4weeks. IL-1β expression also peaked at 4weeks and was then down-regulated. Overall the findings indicate that neuroinflammatory features build up in the first month after hydrocephalus induction implicating marked IL-1β upregulation. The data also show that astrocytes are the main source of IL-1β in this disorder.
脑积水在资源有限的国家尤其普遍，其治疗仍然是一个挑战。然而，未经治疗的脑积水的长期神经病理学变化在很大程度上仍未得到探索。本研究着眼于获得性、慢性脑积水的皮质实质和神经炎症。在 3 周龄大鼠中进行脑室内高岭土注射，然后分别在 1 周、4 周和 8 周存活；匹配的对照大鼠接受盐水注射。在该模型中，先前报道脑室扩大在第 3 周稳定。采用单细胞和三重免疫细胞化学方法，利用细胞计数和密度测定法，突出显示顶叶皮层中的神经元、星形胶质细胞、小胶质细胞和促炎细胞因子白细胞介素（IL）-1β。用 Western blot 监测顶叶皮层和海马体中小胶质细胞蛋白离子钙结合衔接分子 1（Iba1）和 IL-1β的表达。在顶叶皮层中，细胞结构逐渐破坏，神经元密度在诱导后 8 周时显著增加，但在早期时间点没有增加，这表明慢性脑积水持续存在皮质损伤。星形胶质细胞和小胶质细胞肥大以及 Iba1 表达表明胶质细胞激活，在 4 周时达到峰值。IL-1β的表达也在 4 周时达到峰值，然后下调。总的来说，这些发现表明，神经炎症特征在脑积水诱导后第一个月内逐渐形成，表明 IL-1β的显著上调。该数据还表明，星形胶质细胞是该疾病中 IL-1β的主要来源。
