Influence of Inosine on Cerebral Hemodynamics in Space Motion Sickness in Experimental Animals.

Asie N Useinova, Vitalii B Kaliberdenko, Igor D Sapegin, Shanmugaraj Kulanthaivel, Michael V Shterenshis, Maria I Dmitriyevskaya, Keerthanaa Balasundaram
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Abstract

Background: Motion sickness occurs worldwide in healthy individuals regardless of age, ethnicity, or gender. It is an acute disorder; it can also present as a chronic disorder in some individuals. Motion sickness not only includes vomiting and nausea, but also includes other features such as pallor of varying degrees, cold sweating, headache, drowsiness, increased salivation, and cranial pain, which are severe. Some of the other assessment scales can interpret sickness on exposure to virtual or visual stimulation and while travelling in different types of transport.

Aim: The aim of our research is to study the effect of the drug on the level of blood flow and vascular reactivity of cerebral vessels when simulating changes in the cerebral circulation in terrestrial conditions characteristic of hypogravity.

Methods: Chronic experiments were performed on non-anesthetized rabbits with large hemispheres, thalamus and hypothalamus were implanted with the needle-platinum electrodes 150 mm in diameter in the cortex, and local blood flow and vascular reactivity were recorded accordingly. Cerebrovascular disturbances were modeled using an MSAOP (motion sickness of animals in the anti-orthostatic position) with an inclined angle of 45° for 2 hours. Local blood flow (BF) was measured in ml/min/100g of tissue by the method of registration of hydrogen clearance. The vasodilator coefficient of reactivity (CrCO2) was calculated by the ratio of BF against the background of inhalation of a mixture of 7% CO2 with air to the initial BF; vasoconstrictor - in relation to BF on the background of inhalation of 100% O2 to the initial BF (CrO2). A series of experiments were carried out with different routes of drug administration: First, inosine was administered intravenously at a dose of 5 mg/kg immediately before the start of SMS modeling, same dose was administered 30 minutes before the start of exposure. As a control, we used the results of experimental animals under similar conditions without the administration of the drugs.

Results: Inosine has pronounced protective properties in cerebrovascular disorders on the background of space motion sickness (SMS) modeling, which is manifested by normalization of BF and restoration of compensatory reactions of cerebral vessels. In the mechanism of cerebroprotective action of inosine, it is able to correct the metabolic processes, which play an important role and help increase the compensatory capabilities and functional stability of the cerebrovascular system under gravitational influences.

Conclusion: When using inosine orally, the effects are more pronounced than when administered intravenously, which should be taken into account when using it for the prevention of cerebrovascular disorders in extreme conditions.

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肌苷对空间运动病实验动物脑血流动力学的影响。
背景:全球范围内,不论年龄、种族或性别,在健康人群中都可以发生晕动病。这是一种急性疾病;在某些个体中,它也可以表现为慢性疾病。晕动病不仅包括呕吐和恶心,还包括其他症状,如不同程度的苍白、冷汗、头痛、嗜睡、唾液分泌增加和颅脑疼痛,这些症状都很严重。其他一些评估量表可以通过接触虚拟或视觉刺激以及乘坐不同类型的交通工具来解释疾病。目的:我们的研究目的是在模拟以低重力为特征的陆地条件下脑循环变化时,研究药物对脑血管血流水平和血管反应性的影响。方法:在未麻醉的兔大半球、丘脑和下丘脑皮质植入直径为150mm的针铂电极,进行慢性实验,记录局部血流和血管反应性。采用倾斜角度为45°的MSAOP(动物反立位运动病)模型,持续2小时。采用氢清除登记法,以ml/min/100g组织为单位测量局部血流量(BF)。血管扩张反应性系数(CrCO2)是通过在吸入7% CO2与空气混合的背景下与初始BF的比率来计算的;血管收缩剂-在吸入100% O2到初始BF (CrO2)的背景下与BF相关。采用不同给药途径进行一系列实验:首先,在SMS建模开始前立即静脉注射肌苷,剂量为5 mg/kg,在暴露开始前30分钟注射相同剂量。作为对照,我们使用了在相同条件下不给药的实验动物的结果。结果:肌苷在空间运动病(SMS)模型背景下对脑血管疾病具有明显的保护作用,表现为BF的正常化和脑血管代偿反应的恢复。在肌苷的脑保护作用机制中,它能够纠正代谢过程,发挥重要作用,有助于增加重力作用下脑血管系统的代偿能力和功能稳定性。结论:肌苷口服比静脉给药效果更明显,在极端条件下应用肌苷预防脑血管疾病时应考虑到这一点。
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来源期刊
Central nervous system agents in medicinal chemistry
Central nervous system agents in medicinal chemistry Psychology-Neuropsychology and Physiological Psychology
CiteScore
2.10
自引率
0.00%
发文量
21
期刊介绍: Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.
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