Abstract
BackgroundElevated 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.MethodsA 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).ResultsFor 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.ConclusionsICP 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.
Highlights
The regulation of intracranial pressure (ICP) is fundamental in providing a stable environment to enable normal brain function
This study demonstrates continuous ICP monitoring in freely-moving and co-housed rats for up to 50 days with a high degree of stability
We demonstrate that using the epidural space in rodents is safe and provides stable ICP data
Summary
The regulation of intracranial pressure (ICP) is fundamental in providing a stable environment to enable normal brain function. Common techniques for ICP monitoring in clinical practice are intraventricular, parenchymal measurements or lumbar puncture (LP) measurements These methods only provide a short-term pressure reading during these procedures or it is limited to few days, due to a progressively increasing risk of infection and patient mobility [3, 4]. Existing data which are considered “normal” ICP values are derived from examinations performed in patients needing ICP monitoring due to suspected disturbance in ICP or taken from measurements of lumbar CSF pressure This demonstrates a great necessity for consistent and precise ICP monitoring in animal models, where ICP can be measured across the day and over longer periods of time in order to better understand the regulation of ICP. 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
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