Cotton rats (Sigmodon hispidus) with a high prevalence of hydrocephalus without clinical symptoms
Cotton rats (Sigmodon hispidus) with a high prevalence of hydrocephalus without clinical symptoms
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DOI：
10.1111/neup.12776
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发表时间：
2021-12-27
期刊：
影响因子：
2.3
通讯作者：
Kon，Yasuhiro
中科院分区：
文献类型：
--
作者：
Kondoh，Daisuke;Nakamura，Teppei;Kon，Yasuhiro
常压脑积水（NPH）是脑室增大而脑脊液压力不升高的一种疾病，通常发生在晚年，进展缓慢。模拟人类特发性NPH的完整动物模型尚未建立，NPH的发病机制和详细的病理机制尚未完全了解。在本研究中，我们发现在近亲繁殖的棉花大鼠（Sigmodon hispidus）中，脑积水自发性患病率高（34.6%），无临床症状。46只脑积水大鼠均为轻度或中度，均不严重。扩张仅限于侧脑室，未见脑积水大鼠出血、脑室炎、脑膜炎或肿瘤形成。这些结果表明，棉花大鼠脑积水的类型与通讯性特发性NPH相似。组织病理学检查显示，脑积水患者大脑皮层内颗粒层和锥体层（第IV层和第V层）变薄。少量锥体细胞对氟玉C（一种退行性神经元标志物）和离子钙结合接头分子1 （Iba1）免疫反应性小胶质细胞与脑积水大鼠新皮层退行性神经元接触呈阳性，表明脑积水大鼠新皮层的突起或多或少受损。本研究强调棉花大鼠作为阐明特发性NPH病理机制的新模型的候选者。此外，棉花大鼠有一些明显的全身病理表型，如慢性肾脏疾病和代谢紊乱。因此，该模型也可用于研究NPH与其他疾病的合并症。
Normal‐pressure hydrocephalus (NPH) is a condition in which the ventricle is enlarged without elevated cerebrospinal fluid pressure, and it generally develops in later life and progresses slowly. A complete animal model that mimics human idiopathic NPH has not yet been established, and the onset mechanisms and detailed pathomechanisms of NPH are not fully understood. Here, we demonstrate a high spontaneous prevalence (34.6%) of hydrocephalus without clinical symptoms in inbred cotton rats (Sigmodon hispidus). In all 46 hydrocephalic cotton rats, the severity was mild or moderate and not severe. The dilation was limited to the lateral ventricles, and none of the hemorrhage, ventriculitis, meningitis, or tumor formation was found in hydrocephalic cotton rats. These findings indicate that the type of hydrocephalus in cotton rats is similar to that of communicating idiopathic NPH. Histopathological examinations revealed that the inner granular and pyramidal layers (layers IV and V) of the neocortex became thinner in hydrocephalic brains. A small number of pyramidal cells were positive for Fluoro‐Jade C (a degenerating neuron marker) and ionized calcium‐binding adaptor molecule 1 (Iba1)‐immunoreactive microglia were in contact with the degenerating neurons in the hydrocephalic neocortex, suggesting that hydrocephalic cotton rats are more or less impaired projections from the neocortex. This study highlights cotton rats as a candidate for novel models to elucidate the pathomechanism of idiopathic NPH. Additionally, cotton rats have some noticeable systemic pathological phenotypes, such as chronic kidney disease and metabolic disorders. Thus, this model might also be useful for researching the comorbidities of NPH to other diseases.