Background Elevated intracranial pressure (ICP) is observed in association with a range of brain disorders. There is limited insight into the regulatory mechanisms of ICP under physiological conditions, and consequently also under pathological conditions. Thereby, to understand the mechanisms underlying ICP dynamics, precise, valid and long-term ICP recordings are of importance in the preclinical setting. Herein, we used a novel telemetric system for ICP recordings which allowed for long-term recordings in freely-moving rats. The aim was to investigate ICP dynamics under different physiological states and investigate how factors such as surgery/recovery, body position, light–dark, co-housing, weight and anesthesia may influence ICP and its waveforms. Methods A telemetric device was implanted epidurally in rats and signals were recorded continuously for up to 50 days (n = 14). Recording was divided into three experimental periods: a surgical recovery period (RP), a physiological period (PP) and an experimental period (EP). Histology was performed to study the morphology of implanted rats and non-implanted rats (n = 17). Results For the first time, we can demonstrate continuous ICP recordings in freely-moving and co-housed rats for up to 50 days with a high degree of stability. The mean ICP in the recording periods were; RP: 3.2 ± 0.6 mmHg, PP: 5.0 ± 0.6 mmHg and EP: 4.7 ± 0.6 mmHg. In the RP, the ICP was significantly lower compared to the PP (P = 0.0034). Significant light–dark difference in ICP with 21% increase in respiratory slow-wave amplitude was observed in the co-housed animals but not in single-housed animals. The ICP signal was raised during the dark period relative to the light (Δ0.3 ± 0.07 mmHg, P = 0.0043). Administration of anesthesia gave a short-term increase in ICP followed by a significant decrease in ICP. No signs of tissue damage or inflammation were found in the implanted brains. Conclusions ICP dynamics were influenced by several factors such as, use of anesthesia, light–dark difference and housing conditions. Our study demonstrates the importance of performing ICP physiological measurements in freely-moving animals. This has significant implications for moving the preclinical research field forward in order to properly study ICP physiology during disease development and to explore drug targets for alleviating increased ICP.

中文翻译：

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自由活动大鼠颅内压的长期监测；不同生理状态的影响

背景 颅内压 (ICP) 升高与一系列脑部疾病有关。对 ICP 在生理条件下的调节机制的了解有限，因此在病理条件下也是如此。因此，要了解 ICP 动力学的潜在机制，精确、有效和长期的 ICP 记录在临床前设置中很重要。在这里，我们使用了一种新颖的遥测系统进行 ICP 记录，允许在自由移动的大鼠中进行长期记录。目的是研究不同生理状态下的 ICP 动力学，并研究手术/恢复、体位、明暗、合住、体重和麻醉等因素如何影响 ICP 及其波形。方法 将遥测装置植入大鼠硬膜外并连续记录信号长达 50 天（n = 14）。录音分为三个实验期：手术恢复期（RP）、生理期（PP）和实验期（EP）。进行组织学以研究植入大鼠和非植入大鼠 (n = 17) 的形态。结果我们第一次可以在自由移动和共同饲养的大鼠中证明连续 ICP 记录长达 50 天，并且具有高度的稳定性。记录期间的平均 ICP 是；RP：3.2 ± 0.6 mmHg，PP：5.0 ± 0.6 mmHg 和 EP：4.7 ± 0.6 mmHg。在 RP 中，ICP 显着低于 PP (P = 0.0034)。在共同饲养的动物中观察到 ICP 的显着明暗差异，呼吸慢波振幅增加了 21%，但在单独饲养的动物中没有观察到。ICP 信号在相对于光的黑暗时期升高 (Δ0.3 ± 0.07 mmHg, P = 0.0043)。麻醉给药使 ICP 短期增加，随后 ICP 显着降低。在植入的大脑中没有发现组织损伤或炎症的迹象。结论 ICP 动态受多种因素的影响，例如麻醉的使用、明暗差异和住房条件。我们的研究证明了对自由移动的动物进行 ICP 生理测量的重要性。