Background Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by raised cerebrospinal fluid (CSF) pressure in the absence of any intracranial pathology. IIH mainly affects women with obesity between the ages of 15 and 45. Two possible mechanisms that could explain the increased CSF pressure in IIH are excessive CSF production by the choroid plexus (CP) epithelium or impaired CSF drainage from the brain. However, the molecular mechanisms controlling these mechanisms in IIH remain to be determined. Methods In vivo ventriculo-cisternal perfusion (VCP) and variable rate infusion (VRI) techniques were used to assess changes in rates of CSF secretion and resistance to CSF drainage in female and male Wistar rats fed either a control (C) or high-fat (HF) diet (under anaesthesia with 20 μl/100 g medetomidine, 50 μl/100 g ketamine i.p). In addition, CSF secretion and drainage were assessed in female rats following treatment with inflammatory mediators known to be elevated in the CSF of IIH patients: C–C motif chemokine ligand 2 (CCL2), interleukin (IL)-17 (IL-17), IL-6, IL-1β, tumour necrosis factor-α (TNF-α), as well as glucocorticoid hydrocortisone (HC). Results Female rats fed the HF diet had greater CSF secretion compared to those on control diet (3.18 ± 0.12 μl/min HF, 1.49 ± 0.15 μl/min control). Increased CSF secretion was seen in both groups following HC treatment (by 132% in controls and 114% in HF) but only in control rats following TNF-α treatment (137% increase). The resistance to CSF drainage was not different between control and HF fed female rats (6.13 ± 0.44 mmH 2 O min/μl controls, and 7.09 ± 0.26 mmH 2 O min/μl HF). and when treated with CCL2, both groups displayed an increase in resistance to CSF drainage of 141% (controls) and 139% (HF) indicating lower levels of CSF drainage. Conclusions Weight loss and therapies targeting HC, TNF-α and CCL2, whether separately or in combination, may be beneficial to modulate rates of CSF secretion and/or resistance to CSF drainage pathways, both factors likely contributing to the raised intracranial pressure (ICP) observed in female IIH patients with obesity.

中文翻译：

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饮食和细胞因子对大鼠脑脊液动力学的调节

背景特发性颅内高压 (IIH) 是一种神经系统疾病，其特征是在没有任何颅内病变的情况下脑脊液 (CSF) 压力升高。IIH 主要影响 15 至 45 岁的肥胖女性。可以解释 IIH 中脑脊液压力增加的两种可能机制是脉络丛 (CP) 上皮产生过多的脑脊液或脑脊液引流受损。然而，在 IIH 中控制这些机制的分子机制仍有待确定。方法 体内脑室-脑池灌注 (VCP) 和可变速率输注 (VRI) 技术用于评估雌性和雄性 Wistar 大鼠的脑脊液分泌速率和脑脊液引流阻力的变化(HF) 饮食（在麻醉下用 20 μl/100 g 美托咪定，50 μl/100 g 氯胺酮 ip)。此外，在用已知在 IIH 患者脑脊液中升高的炎症介质治疗后，评估了雌性大鼠的脑脊液分泌和引流：C-C 基序趋化因子配体 2 (CCL2)、白细胞介素 (IL)-17 (IL-17) 、IL-6、IL-1β、肿瘤坏死因子-α (TNF-α) 以及糖皮质激素氢化可的松 (HC)。结果 喂食 HF 饮食的雌性大鼠与对照饮食的雌性大鼠相比具有更高的 CSF 分泌（3.18 ± 0.12 μl/min HF，1.49 ± 0.15 μl/min 对照）。HC 治疗后两组的 CSF 分泌均增加（对照组增加 132%，HF 增加 114%），但仅在 TNF-α 治疗后的对照组大鼠中（增加 137%）。CSF 引流阻力在对照和 HF 喂养的雌性大鼠之间没有差异（6.13 ± 0.44 mmH 2 O min/μl 对照，和 7.09 ± 0.26 mmH 2 O min/μl HF）。当用 CCL2 治疗时，两组对 CSF 引流的抵抗力增加了 141%（对照组）和 139%（HF），表明 CSF 引流水平较低。结论 减肥和针对 HC、TNF-α 和 CCL2 的治疗，无论是单独还是联合，都可能有益于调节 CSF 分泌率和/或对 CSF 引流通路的抵抗，这两个因素都可能导致颅内压 (ICP) 升高在肥胖的女性 IIH 患者中观察到。