Department of Neurosurgery, Hadassah-Hebrew University Medical Center, Kiryat Hadassah, 91120, Jerusalem, Israel.
Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel.
Fluids Barriers CNS. 2021 Sep 16;18(1):42. doi: 10.1186/s12987-021-00274-z.
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.
先前的颅内压（ICP）动力学模型并未包括脑间质液（ISF）的流动以及脑肿胀发生时其流动阻力的变化。我们试图开发一种数学模型，该模型纳入了脑 ISF 整体流动的阻力，以更好地模拟在以脑肿胀为主的病理生理变化，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 流动及其与脑脊液（CSF）流动和脑血流（CBF）的相互作用的表示。该模型基于具有四个颅内隔室的电模拟电路：（1）蛛网膜下腔，（2）脑，（3）脑室，（4）脑血管和颅外脊髓鞘。我们在稳态下确定了颅内隔室内的压力和体积变化，并模拟了生理干扰，包括快速向颅内空间注入液体、过度通气和低通气。我们模拟了 CSF 和脑 ISF 流动阻力或吸收的变化，以模拟脑积水、脑水肿，并模拟血脑屏障（BBB）的破坏。
该模型准确地再现了颅内生理学的公认特征，包括快速注入液体时呈指数样的压力-体积曲线、随着 ICP 升高而增加的 ICP 脉搏压力、CSF 流出阻力增加导致的脑积水，以及与过度通气和低通气相关的变化。重要的是，模拟脑 ISF 流动阻力增加导致脑水肿的模型模拟了脑肿胀的关键特征，包括升高的 ICP、脑体积增加、脑室体积显著减少以及蛛网膜下腔收缩。同样，跨 BBB 液体流动阻力降低会导致 ICP 呈指数样升高和脑室塌陷。
该模型准确地描绘了特定病理生理条件下不同颅内隔室内压力、体积和流动阻力之间发生的复杂相互作用。在模拟脑 ISF 的整体流动阻力时，它可能成为改进脑损伤后发生的脑水肿和血脑屏障破坏模型的平台。
