Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5A Butlerov Str., 117485 Moscow, Russia.
Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department, 43 Donskaya Str., 115419 Moscow, Russia.
Int J Mol Sci. 2021 Dec 17;22(24):13544. doi: 10.3390/ijms222413544.
Two classical surgical approaches for intraluminal filament middle cerebral artery occlusion (MCAO), the Longa et al. (LM) and Koizumi et al. methods (KM), are used as alternatives in preclinical studies to induce stroke in rodents. Comparisons of these MCAO models in mice showed critical differences between them along with similarities (Smith et al. 2015; Morris et al. 2016). In this study, a direct comparison of MCAO-KM and MCAO-LM in rats was performed. Three days after MCAO, infarct volume, mortality rate, neurological deficit, and weight loss were similar in these models. MCAO-LM rats showed an increase in ACTH levels, while MCAO-KM rats demonstrated elevated corticosterone and interleukin-1β in blood serum. Corticosterone accumulation was detected in the frontal cortex (FC) and the hippocampus of the MCAO-KM group. IL1β beta increased in the ipsilateral hippocampus in the MCAO-KM group and decreased in the contralateral FC of MCAO-LM rats. Differences revealed between MCAO-KM and MCAO-LM suggest that corticosterone and interleukin-1β release as well as hippocampal accumulation is more expressed in MCAO-KM rats, predisposing them to corticosterone-dependent distant neuroinflammatory hippocampal damage. The differences between two models, particularly, malfunction of the hypothalamic-pituitary-adrenal axis, should be considered in the interpretation, comparison, and translation of pre-clinical experimental results.
两种经典的管腔内栓线大脑中动脉闭塞（MCAO）手术方法，即 Longa 等（LM）和 Koizumi 等（KM）方法，被用作临床前研究中诱导啮齿动物中风的替代方法。这些 MCAO 模型在小鼠中的比较显示出它们之间存在关键差异，同时也存在相似之处（Smith 等人，2015 年；Morris 等人，2016 年）。在这项研究中，对大鼠的 MCAO-KM 和 MCAO-LM 进行了直接比较。MCAO 后 3 天，这些模型中的梗死体积、死亡率、神经功能缺损和体重减轻相似。MCAO-LM 大鼠的 ACTH 水平升高，而 MCAO-KM 大鼠的皮质酮和白细胞介素-1β在血清中升高。皮质酮在 MCAO-KM 组的额皮质（FC）和海马中积累。IL1β beta 在 MCAO-KM 组的同侧海马中增加，而在 MCAO-LM 大鼠的对侧 FC 中减少。MCAO-KM 和 MCAO-LM 之间揭示的差异表明，皮质酮和白细胞介素-1β的释放以及海马的积累在 MCAO-KM 大鼠中更为明显，使它们易患皮质酮依赖性的远处神经炎症性海马损伤。这两种模型之间的差异，特别是下丘脑-垂体-肾上腺轴的功能障碍，在解释、比较和翻译临床前实验结果时应予以考虑。
