Blood-brain barrier disruption and edema formation due to prolonged starvation in wild-type mice.

IF 2.3 4区 医学 Q3 CLINICAL NEUROLOGY Brain Circulation Pub Date : 2024-06-26 eCollection Date: 2024-04-01 DOI:10.4103/bc.bc_88_23
M Ibrahim Hossain, Mehjabeen Haque, Maria Akter, Sabrina Sharmin, Asif Ahmed
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Abstract

Introduction: Different types of diseases have been treated by restricted caloric intake or fasting. Although during this long time, fasting protective measures, for example, supplements, are given to the patients to protect vital organs such as the liver and kidney, little attention is given to the brain. The current research aims to investigate hypoglycemia due to prolonged fasting disrupts blood-brain barrier (BBB) in mice.

Materials and methods: Immunohistochemistry (IHC) and in situ hybridization (ISH) techniques were used to examine the expression of different genes. Evans blue extravasation and wet-dry technique were performed to evaluate the integrity of BBB and the formation of brain edema, respectively.

Results: We confirmed that hypoglycemia affected mice fasting brain by examining the increased expression of glucose transporter protein 1 and hyperphosphorylation of tau protein. We subsequently found downregulated expression of some genes, which are involved in maintaining BBB such as vascular endothelial growth factor (VEGF) in astrocytes and claudin-5 (a vital component of BBB) and VEGF receptor (VEGFR1) in endothelial cells by ISH. We also found that prolonged fasting caused the brain endothelial cells to express lipocalin-2, an inflammatory marker of brain endothelial cells. We performed Evans blue extravasation to show more dye was retained in the brain of fasted mice than in control mice as a result of BBB disruption. Finally, wet-dry method showed that the brain of prolonged fasted mice contained significantly higher amount of water confirming the formation of brain edema. Therefore, special attention should be given to the brain during treatment with prolonged fasting for various diseases.

Conclusions: Our results demonstrated that hypoglycemia due to prolonged fasting disrupts BBB and produces brain edema in wild-type mice, highlighting the importance of brain health during treatment with prolonged fasting.

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野生型小鼠长期饥饿导致血脑屏障破坏和水肿形成。
导言:人们一直通过限制热量摄入或禁食来治疗不同类型的疾病。虽然在长时间禁食的过程中,会给患者提供一些禁食保护措施,如补充营养品,以保护肝脏和肾脏等重要器官,但很少有人关注大脑。目前的研究旨在探讨长期禁食导致的低血糖会破坏小鼠的血脑屏障(BBB):免疫组化(IHC)和原位杂交(ISH)技术用于检测不同基因的表达。伊文思蓝外渗和湿干技术分别用于评估 BBB 的完整性和脑水肿的形成:结果:通过检测葡萄糖转运蛋白 1 的表达增加和 tau 蛋白的过度磷酸化,我们证实低血糖影响了小鼠的空腹脑。随后,我们发现一些参与维持 BBB 的基因表达下调,如星形胶质细胞中的血管内皮生长因子(VEGF)、内皮细胞中的 claudin-5(BBB 的重要组成部分)和 VEGF 受体(VEGFR1)。我们还发现,长期禁食会导致脑内皮细胞表达脂联素-2,这是一种脑内皮细胞的炎症标志物。我们进行了伊文思蓝外渗实验,结果表明禁食小鼠脑内保留的染料多于对照组小鼠,这是 BBB 被破坏的结果。最后,干湿法显示,长期禁食小鼠大脑中的含水量明显增加,证实了脑水肿的形成。因此,在对各种疾病进行长期禁食治疗时,应特别关注大脑:我们的研究结果表明,长期禁食导致的低血糖会破坏野生型小鼠的BBB并产生脑水肿,这凸显了长期禁食治疗期间脑健康的重要性。
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来源期刊
Brain Circulation
Brain Circulation Multiple-
自引率
5.30%
发文量
31
审稿时长
16 weeks
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