粒细胞集落刺激因子在辐射诱导脑损伤模型中的修复、神经保护及抗神经退行性变作用
Reparative, Neuroprotective and Anti-neurodegenerative Effects of Granulocyte Colony Stimulating Factor in Radiation-Induced Brain Injury Model.
作者信息
Gürkan Gökhan, Atasoy Özüm, Çini Nilsu, Sever İbrahim Halil, Özkul Bahattin, Yaprak Gökhan, Şirin Cansın, Uyanıkgil Yiğit, Kızmazoğlu Ceren, Erdoğan Mümin Alper, Erbaş Oytun
机构信息
Department of Neurosurgery, Izmir Katip Celebi University Atatürk Training and Research Hospital, Izmir, Turkey.
Department of Radiation Oncology, Kartal City Hospital, Istanbul, Turkey.
出版信息
J Korean Neurosurg Soc. 2023 Sep;66(5):511-524. doi: 10.3340/jkns.2023.0049. Epub 2023 May 11.
OBJECTIVE
This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically.
METHODS
This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals.
RESULTS
G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels.
CONCLUSION
In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.
目的
本动物模型旨在比较接受脑部照射且未接受额外治疗（仅注射生理盐水）的大鼠组和接受脑部照射并接受粒细胞集落刺激因子（G-CSF）治疗的大鼠组。此外，通过磁共振（MR）成像和组织病理学检查G-CSF对脑功能的影响。
方法
本研究使用了24只雌性Wistar白化大鼠。在研究开始时开始给药（生理盐水或G-CSF），并在全脑放疗（WBRT）后持续15天。WBRT在研究开始的第7天进行。在15天结束时，进行行为测试，包括三室社交性测试、旷场试验和被动回避学习测试。行为测试后，对动物进行磁共振波谱检查。在研究结束时，对所有动物实施颈椎脱臼。
结果
G-CSF治疗对三室社交性测试、旷场试验和被动回避学习测试的结果、海马角（CA）1、CA3和浦肯野神经元计数以及脑源性神经营养因子和突触后密度蛋白-95的脑水平产生了积极影响。然而，G-CSF治疗降低了胶质纤维酸性蛋白免疫染色指数以及丙二醛、肿瘤坏死因子-α、核因子κB和乳酸的脑水平。此外，在磁共振波谱检查中，G-CSF对脑乳酸水平有可逆作用。
结论
在这个首次设计的评估G-CSF作用的脑部照射动物模型中，我们观察到G-CSF具有修复、神经保护和抗神经退行性作用，并增加了神经营养因子表达、神经元计数和形态变化。此外，G-CSF在磁共振波谱检查和脑材料中具有已证实的降低乳酸的作用。
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