Impaired neurogenesis with reactive astrocytosis in the hippocampus in a porcine model of acquired hydrocephalus.
Impaired neurogenesis with reactive astrocytosis in the hippocampus in a porcine model of acquired hydrocephalus.
复制标题
在获得性脑积水的猪模型中，海马反应性星形细胞增多症神经发生受损。
DOI：
10.1016/j.expneurol.2023.114354
复制
发表时间：
2023
影响因子：
5.3
通讯作者：
McAllister2nd,JamesP
中科院分区：
文献类型：
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作者：
Garcia-Bonilla,Maria;Nair,Arjun;Moore,Jason;Castaneyra-Ruiz,Leandro;Zwick,SarahH;Dilger,RyanN;Fleming,StephenA;Golden,RebeccaK;Talcott,MichaelR;Isaacs,AlbertM;LimbrickJr,DavidD;McAllister2nd,JamesP
背景脑积水是一种神经系统疾病，在美国的发病率为0.3-0.7/1000活产。脑室肥大、脑室周围白色物质改变、炎症和神经胶质增生是与这种疾病相关的神经病理学。我们假设海马结构和颗粒下区神经发生的改变，在未经治疗的脑积水和相关的识别记忆deficits.MethodsHydrocephalus脑积水是由脑池内注射高岭土在国内幼年猪（43.6 ± 9.8天）。与之匹配的假手术对照组接受类似的生理盐水注射。诱导后14 ± 4天和36 ± 8天进行MRI测量心室容积和/或海马和鼻周大小。在高岭土诱导前后一周评估识别记忆。结果脑积水猪在诱导后14 ± 4天海马宽度和嗅周皮质厚度明显减小（p< 0.05）。在处死时（诱导后36 ± 8天），与假手术对照组相比，脑积水猪中检测到脑室显著扩张（p= 0.005）。处死时，脑积水猪的背侧海马面积减少（p= 0.035）23.4%。脑积水猪背侧海马颗粒下区神经元前体细胞（doublecortin+细胞）和神经元的百分比分别下降32.35%和19.74%（p< 0.01）。反应性星形胶质细胞（波形蛋白+）的百分比增加了48.7%（p= 0.041）。相比之下，脑积水猪背侧海马中的小胶质细胞减少（p= 0.014）55.74%。有没有差异的识别指数，学习和记忆的总结性措施，一周前和诱导后hydrocephalus.ConclusionIn未处理的幼年猪，获得性脑积水引起的形态学改变，减少神经发生，并增加反应性星形胶质细胞在海马和嗅周皮质。
BackgroundHydrocephalus is a neurological disease with an incidence of 0.3–0.7 per 1000 live births in the United States. Ventriculomegaly, periventricular white matter alterations, inflammation, and gliosis are among the neuropathologies associated with this disease. We hypothesized that hippocampus structure and subgranular zone neurogenesis are altered in untreated hydrocephalus and correlate with recognition memory deficits.MethodsHydrocephalus was induced by intracisternal kaolin injections in domestic juvenile pigs (43.6 ± 9.8 days). Age-matched sham controls received similar saline injections. MRI was performed to measure ventricular volume, and/or hippocampal and perirhinal sizes at 14 ± 4 days and 36 ± 8 days post-induction. Recognition memory was assessed one week before and after kaolin induction. Histology and immunohistochemistry in the hippocampus were performed at sacrifice.ResultsThe hippocampal width and the perirhinal cortex thickness were decreased (p< 0.05) in hydrocephalic pigs 14 ± 4 days post-induction. At sacrifice (36 ± 8 days post-induction), significant expansion of the cerebral ventricles was detected (p= 0.005) in hydrocephalic pigs compared with sham controls. The area of the dorsal hippocampus exhibited a reduction (p= 0.035) of 23.4% in the hydrocephalic pigs at sacrifice. Likewise, in hydrocephalic pigs, the percentages of neuronal precursor cells (doublecortin+ cells) and neurons decreased (p< 0.01) by 32.35%, and 19.74%, respectively, in the subgranular zone of the dorsal hippocampus. The percentage of reactive astrocytes (vimentin+) was increased (p= 0.041) by 48.7%. In contrast, microglial cells were found to decrease (p= 0.014) by 55.74% in the dorsal hippocampus in hydrocephalic pigs. There was no difference in the recognition index, a summative measure of learning and memory, one week before and after the induction of hydrocephalus.ConclusionIn untreated juvenile pigs, acquired hydrocephalus caused morphological alterations, reduced neurogenesis, and increased reactive astrocytosis in the hippocampus and perirhinal cortex.