研究中风中艾滋病毒相关脑损伤的可重现小鼠模型。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2024-10-02 DOI:10.1016/j.brainres.2024.149256

Mohd Salman , Golnoush Mirzahosseini , Lina Zhou , Sandip Godse , Namita Sinha , Santosh Kumar , Tauheed Ishrat

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引用次数: 0

摘要

背景：新出现的临床和流行病学数据表明，人类免疫缺陷病毒（HIV）与中风风险增加和脑损伤加重有关。我们的目的是模拟临床情况，建立一个可重复的感染 HIV 的光栓性中风小鼠模型：为了评估 HIV 感染对中风的影响，雄性 C57BL/6 小鼠被 EcoHIV（p24 2-4 × 106/只小鼠；静脉注射）或模拟对照组感染。感染四周后，采用光栓法诱发中风。72小时后，对小鼠进行猫步障碍测试，并对中风结果进行安乐死：结果：与模拟对照组相比，EcoHIV感染小鼠在pt-MCAO后表现出更大的梗死、脑水肿、更高的IgG外渗、出血转化和步态障碍。与模拟 pt-MCAO 相比，EcoHIV 感染的小鼠血浆和大脑中的 IFN-y 水平较高，IL-6 水平较低，表明免疫激活，但不影响 IL-1β 和 MCP-1，表明炎症未发生改变。EcoHIV 表明氧化应激标志物（硝基酪氨酸和 4-羟基壬烯醛）和硫氧还蛋白相互作用蛋白表达增加。此外，EcoHIV 感染明显激活了小胶质细胞和星形胶质细胞：该动物模型可靠且与临床相关，可用于今后研究中风艾滋病患者的病理生理机制和开发新的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

A reproducible murine model of studying HIV-associated brain damage in stroke

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A reproducible murine model of studying HIV-associated brain damage in stroke

Background

Emerging clinical and epidemiological data indicates that human immunodeficiency virus (HIV) is associated with an increased risk of stroke and aggravated brain damage. We aimed to develop a reproducible murine model of photothrombotic-stroke with HIV infection that mimics the clinical situation.

Method

To evaluate the impact of HIV infection on stroke, male C57BL/6 mice were infected with EcoHIV (p24 2-4 × 10⁶/mouse; i.v.) or mock control. Four weeks post-infection, a stroke was induced by the photothrombotic method (pt-MCAO). After 72 h, a catwalk test was performed for gait impairments, and mice were euthanized for stroke outcomes.

Results

EcoHIV-infection exhibited a larger infarction, brain edema, higher IgG extravasation, hemorrhagic transformation, and gait impairments following pt-MCAO vs mock control. EcoHIV-infected mice showed higher levels of IFN-y and lower levels of IL-6, indicating immune activation without affecting IL-1β and MCP-1 in plasma and brain compared to mock pt-MCAO, suggesting unaltered inflammation. EcoHIV-infection showed increased oxidative stress markers (nitrotyrosine, and 4-hydroxynonenal) and thioredoxin interacting protein expression. Further, EcoHIV-infection significantly activated the microglia and astrocyte cells.

Conclusions

This animal model would be reliable and clinically relevant to future studies investigating pathophysiological mechanisms and developing new therapeutic approaches in stroke patients with HIV conditions.

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.