Interactions of brain, blood, and CSF: a novel mathematical model of cerebral edema

Abstract

Background 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. Methods 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). Results 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. Conclusions 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.

Intractable hypotension caused by acute superior vena cava obstruction after lung cancer surgery: a case report

“…A certain average blood pressure is maintained, with cerebral perfusion ensured and brain tissue damage caused by ischemia and hypoxia reduced [2]. For the existing SVC syndrome before surgery, the head position should be properly elevated during the operation to avoid the compression of the neck vein, promoting the cerebral venous return through the SVC-speci c collateral circulation vein and reducing the brain pressure as well as the risk of cerebral edema [2]; Hyperventilation through a ventilator can reduce PCO2, cerebrovascular contraction, and craniocerebral pressure as well as relieve brain edema [13]; Preventive use of hormone drugs can reduce cell permeability, improve the tolerance of brain cells, and prevent the occurrence of brain edema [2]; The application of mannitol and diuretics can also reduce intracranial pressure and hinder the further progression of brain edema [14]; The ice pack can cool the brain in vitro, reduce the metabolism of brain tissue, and relieve the damage of brain tissue caused by edema [15]; If acute SVC obstruction due to surgical reasons is suspected, it is critical to communicate with the surgeon immediately to remove the obstruction in time. Cardiopulmonary bypass support should be applied if necessary [2]; Finally, attention should be paid to the risk of pulmonary embolism in the case of cross-clamping SVC in thoracic surgery for the reason that the prolonged occlusion of the SVC can cause blood clots [2].…”

Longitudinal assessment of ventricular volume trajectories in early-stage schizophrenia: evidence of both enlargement and shrinkage

“…The Monro-Kellie doctrine suggests that microedema can cause a shift in brain compartment volumes, resulting in a detectable decrease in ventricular volume [ 48 – 49 ]. This could explain the observed ventricular shrinkage in early-stage schizophrenia, as there is evidence of inflammation during this phase [ 50 ].…”

Measurements of cerebrospinal fluid production: a review of the limitations and advantages of current methodologies

“…(3) The compliance of the subarachnoid space in response to changes in vascular volume might result in erroneous values of CSF production. In particular, draining CSF from the subarachnoid space will lower the pressure of that compartment, resulting in lesser absorption of CSF into the superior sagittal sinus [ 88 ].…”