BackgroundElevated intracranial pressure (ICP) is observed in association with a range of brain disorders. One of these challenging disorders is idiopathic intracranial hypertension (IIH), characterized by raised ICP of unknown cause with significant morbidity and limited therapeutic options. In this review, special focus is put on the preclinical research performed in order to understand the pathophysiology behind ICP regulation and IIH. This includes cerebrospinal fluid dynamics, molecular mechanisms underlying disturbances in brain fluids leading to elevated ICP, role of obesity in IIH, development of an IIH model and ICP measurements in rodents. The review also discusses existing and new drug targets for IIH that have been evaluated in vivo.ConclusionsICP monitoring in rodents is challenging and different methods have been applied. Some of these methods are invasive, depend on use of anesthesia and only allow short-term monitoring. Long-term ICP recordings are needed to study IIH but existing methods are hampered by several limitations. As obesity is one of the most common risk factors for IIH, a rodent obese model has been developed that mimics some key aspects of IIH. The most commonly used drugs for IIH have been evaluated in vivo for their efficacy at lowering ICP in the existing animal models. These studies suggest these drugs, including acetazolamide, might have limited or no reducing effect on ICP. Two drug targets that can impact ICP in healthy rodents are topiramate and a glucagon-like peptide-1 receptor (GLP-1R) agonist. However, it remains to evaluate their effect in an IIH model with more precise and valid ICP monitoring system. Therefore, continued evaluation in the preclinical research with refined tools is of great importance to further understand the pathophysiology behind disorders with raised ICP and to explore new drug targets.

中文翻译：

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特发性颅内高压相关颅内压调节的临床前更新


背景观察到颅内压（ICP）升高与一系列脑部疾病有关。其中一种具有挑战性的疾病是特发性颅内高压 (IIH)，其特征是不明原因的 ICP 升高，发病率高且治疗选择有限。在这篇综述中，特别关注为了解 ICP 调节和 IIH 背后的病理生理学而进行的临床前研究。这包括脑脊液动力学、脑液紊乱导致 ICP 升高的分子机制、肥胖在 IIH 中的作用、IIH 模型的开发以及啮齿类动物的 ICP 测量。该综述还讨论了已在体内评估的 IIH 的现有和新药物靶点。结论啮齿类动物的 ICP 监测具有挑战性，并且已经应用​​了不同的方法。其中一些方法是侵入性的，依赖于麻醉的使用，并且只能进行短期监测。研究 IIH 需要长期 ICP 记录，但现有方法受到一些限制。由于肥胖是 IIH 最常见的危险因素之一，因此开发了一种啮齿动物肥胖模型来模拟 IIH 的一些关键方面。最常用的 IIH 药物已在现有动物模型中对其降低 ICP 的功效进行了体内评估。这些研究表明这些药物，包括乙酰唑胺，对 ICP 的降低作用可能有限或没有。托吡酯和胰高血糖素样肽 1 受体 (GLP-1R) 激动剂是两种可影响健康啮齿动物 ICP 的药物靶点。然而，仍然需要通过更精确和有效的 ICP 监测系统来评估它们在 IIH 模型中的效果。 因此，利用完善的工具持续评估临床前研究对于进一步了解ICP升高疾病背后的病理生理学并探索新的药物靶点具有重要意义。