Previous models of intracranial pressure (ICP) dynamics have not included flow of cerebral interstitial fluid (ISF) and changes in resistance to its flow when brain swelling occurs. We sought to develop a mathematical model that incorporates resistance to the bulk flow of cerebral ISF to better simulate the physiological changes that occur in pathologies in which brain swelling predominates and to assess the model’s ability to depict changes in cerebral physiology associated with cerebral edema. We developed a lumped parameter model which includes a representation of cerebral ISF flow within brain tissue and its interactions with CSF flow and cerebral blood flow (CBF). The model is based on an electrical analog circuit with four intracranial compartments: the (1) subarachnoid space, (2) brain, (3) ventricles, (4) cerebral vasculature and the extracranial spinal thecal sac. We determined changes in pressure and volume within cerebral compartments at steady-state and simulated physiological perturbations including rapid injection of fluid into the intracranial space, hyperventilation, and hypoventilation. We simulated changes in resistance to flow or absorption of CSF and cerebral ISF to model hydrocephalus, cerebral edema, and to simulate disruption of the blood–brain barrier (BBB). The model accurately replicates well-accepted features of intracranial physiology including the exponential-like pressure–volume curve with rapid fluid injection, increased ICP pulse pressure with rising ICP, hydrocephalus resulting from increased resistance to CSF outflow, and changes associated with hyperventilation and hypoventilation. Importantly, modeling cerebral edema with increased resistance to cerebral ISF flow mimics key features of brain swelling including elevated ICP, increased brain volume, markedly reduced ventricular volume, and a contracted subarachnoid space. Similarly, a decreased resistance to flow of fluid across the BBB leads to an exponential-like rise in ICP and ventricular collapse. The model accurately depicts the complex interactions that occur between pressure, volume, and resistances to flow in the different intracranial compartments under specific pathophysiological conditions. In modelling resistance to bulk flow of cerebral ISF, it may serve as a platform for improved modelling of cerebral edema and blood–brain barrier disruption that occur following brain injury.

中文翻译：

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脑、血液和脑脊液的相互作用：一种新的脑水肿数学模型

以前的颅内压 (ICP) 动力学模型不包括脑间质液 (ISF) 的流动以及发生脑肿胀时对其流动的阻力变化。我们试图开发一个数学模型，该模型结合了对脑 ISF 大量流动的阻力，以更好地模拟在以脑肿胀为主的病理中发生的生理变化，并评估该模型描述与脑水肿相关的脑生理变化的能力。我们开发了一个集总参数模型，其中包括脑组织内脑 ISF 流量的表示及其与 CSF 流量和脑血流量 (CBF) 的相互作用。该模型基于具有四个颅内隔室的电气模拟电路：（1）蛛网膜下腔，（2）大脑，（3）心室，(4)脑血管和颅外脊髓鞘囊。我们确定了稳态下脑室内压力和体积的变化，并模拟了生理扰动，包括快速将液体注入颅内空间、换气过度和换气不足。我们模拟了脑脊液和脑 ISF 流动或吸收阻力的变化，以模拟脑积水、脑水肿，并模拟血脑屏障 (BBB) 的破坏。该模型准确地复制了公认的颅内生理学特征，包括快速注液时的指数样压力-体积曲线、随着 ICP 升高而增加的 ICP 脉压、因 CSF 流出阻力增加而导致的脑积水，以及与换气过度和换气不足相关的变化。重要的，对脑 ISF 流动阻力增加的脑水肿建模模拟了脑肿胀的关键特征，包括 ICP 升高、脑容量增加、心室容量显着减少和蛛网膜下腔收缩。类似地，流经 BBB 的流体阻力降低会导致 ICP 和心室塌陷呈指数上升。该模型准确地描述了在特定病理生理条件下不同颅内隔室中的压力、体积和流动阻力之间发生的复杂相互作用。在对脑 ISF 大量流动的阻力建模时，它可以作为改进脑损伤后发生的脑水肿和血脑屏障破坏建模的平台。