Department of Anatomy, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Department of Anatomy, College of Medicine, University of Ibadan, Ibadan, Nigeria,
Pediatr Neurosurg. 2020;55(5):244-253. doi: 10.1159/000510603. Epub 2020 Oct 27.
Hydrocephalus is a disorder in which the circulation of cerebrospinal fluid is altered in a manner that leads to its accumulation in the ventricles and subarachnoid space. Its impact on the neuronal density and networks in the overlying cerebral cortex in a time-dependent neonatal hydrocephalic process is largely unknown. We hypothesize that hydrocephalus will affect the cytoarchitecture of the cerebral cortical mantle of neonatal hydrocephalic mice, which will in turn modify sensorimotor processing and neurobehaviour.
The purpose of this study is to probe the effect of hydrocephalus on 3 developmental milestones (surface righting reflex, cliff avoidance reflex, and negative geotaxis) and on cortical neuronal densities in neonatal hydrocephalic mice.
Hydrocephalus was induced in 1-day-old mice by intracisternal injection of sterile kaolin suspension. The pups were tested for reflex development and sensorimotor ability using surface righting reflex (PND 5, 7, and 9), cliff avoidance (PND 6), and negative geotaxis (PND 10 and 12) prior to their sacrifice on PND 7, 14, and 21. Neuronal density and cortical thickness in the sensorimotor cortex were evaluated using atlas-based segmentation of the neocortex and boundary definition in 4-μm paraffin-embedded histological sections with hematoxylin and eosin as well as cresyl violet stains.
Surface righting and cliff avoidance activities were significantly impaired in hydrocephalic pups but no statistically significant difference was observed in negative geotaxis in both experimental and control pups. The neuronal density of the sensorimotor cortex was significantly higher in hydrocephalic mice than in age-matched controls on PND 14 and 21 (373.20 ± 21.54 × 10-6 μm2 vs. 157.70 ± 21.88 × 10-6 μm2; 230.0 ± 44.1 × 10-6 μm2 vs. 129.60 ± 3.72 × 10-6 μm2, respectively; p < 0.05). This was accompanied by reduction in the cortical thickness (µm) in the hydrocephalic mice on PND 7 (2,409 ± 43.37 vs. 3,752 ± 65.74, p < 0.05), PND 14 (2,035 ± 322.10 vs. 4,273 ± 67.26, p < 0.05), and PND 21 (1,676 ± 33.90 vs. 4,945 ± 81.79, p < 0.05) compared to controls.
In this murine model of neonatal hydrocephalus, the quantitative changes in the cortical neuronal population may play a role in the observed changes in neurobehavioural findings.
脑积水是一种脑脊液循环发生改变的疾病，导致其在脑室和蛛网膜下腔积聚。在新生儿脑积水的时间依赖性过程中，脑积水对覆盖大脑皮层的神经元密度和网络的影响在很大程度上是未知的。我们假设脑积水将影响新生脑积水小鼠大脑皮层盖的细胞结构，这反过来又会改变感觉运动处理和神经行为。
本研究旨在探讨脑积水对新生脑积水小鼠 3 项发育里程碑（表面翻身反射、悬崖回避反射和负趋地性）和皮层神经元密度的影响。
通过向 1 日龄小鼠的脑室内注射无菌高岭土悬浮液来诱导脑积水。在 PND 5、7 和 9 时，使用表面翻身反射（PND 5、7 和 9）、悬崖回避（PND 6）和负趋地性（PND 10 和 12）对新生脑积水小鼠进行反射发育和感觉运动能力测试，然后在 PND 7、14 和 21 时进行尸检。使用基于图谱的新皮层分割和苏木精-伊红以及甲苯胺蓝染色的 4μm 石蜡包埋组织学切片中的边界定义，评估感觉运动皮层中的神经元密度和皮质厚度。
在脑积水幼鼠中，表面翻身和悬崖回避活动明显受损，但在实验组和对照组幼鼠中，负趋地性均无统计学显著差异。在 PND 14 和 21 时，与年龄匹配的对照组相比，感觉运动皮层的神经元密度在脑积水小鼠中显著更高（373.20 ± 21.54×10-6μm2 比 157.70 ± 21.88×10-6μm2；230.0 ± 44.1×10-6μm2 比 129.60 ± 3.72×10-6μm2，p < 0.05）。这伴随着脑积水小鼠皮质厚度（µm）的减少，在 PND 7（2,409 ± 43.37 比 3,752 ± 65.74，p < 0.05）、PND 14（2,035 ± 322.10 比 4,273 ± 67.26，p < 0.05）和 PND 21（1,676 ± 33.90 比 4,945 ± 81.79，p < 0.05）与对照组相比。
在这种新生脑积水的小鼠模型中，皮质神经元群体的定量变化可能在观察到的神经行为发现变化中起作用。
