Cerebrospinal fluid (CSF) and brain tissue sodium levels increase during migraine. However, little is known regarding the underlying mechanisms of sodium homeostasis disturbance in the brain during the onset and propagation of migraine. Exploring the cause of sodium dysregulation in the brain is important, since correction of the altered sodium homeostasis could potentially treat migraine. Under the hypothesis that disturbances in sodium transport mechanisms at the blood-CSF barrier (BCSFB) and/or the blood-brain barrier (BBB) are the underlying cause of the elevated CSF and brain tissue sodium levels during migraines, we developed a mechanistic, differential equation model of a rat's brain to compare the significance of the BCSFB and the BBB in controlling CSF and brain tissue sodium levels. The model includes the ventricular system, subarachnoid space, brain tissue and blood. Sodium transport from blood to CSF across the BCSFB, and from blood to brain tissue across the BBB were modeled by influx permeability coefficients PBCSFB and PBBB, respectively, while sodium movement from CSF into blood across the BCSFB, and from brain tissue to blood across the BBB were modeled by efflux permeability coefficients PBCSFB′ and PBBB′, respectively. We then performed a global sensitivity analysis to investigate the sensitivity of the ventricular CSF, subarachnoid CSF and brain tissue sodium concentrations to pathophysiological variations in PBCSFB, PBBB, PBCSFB′ and PBBB′. Our results show that the ventricular CSF sodium concentration is highly influenced by perturbations of PBCSFB, and to a much lesser extent by perturbations of PBCSFB′. Brain tissue and subarachnoid CSF sodium concentrations are more sensitive to pathophysiological variations of PBBB and PBBB′ than variations of PBCSFB and PBCSFB′ within 30 min of the onset of the perturbations. However, PBCSFB is the most sensitive model parameter, followed by PBBB and PBBB′, in controlling brain tissue and subarachnoid CSF sodium levels within 3 h of the perturbation onset.

中文翻译：

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偏头痛期间血脑脊液和血脑屏障对脑脊液和脑组织钠水平的调节

脑脊液 (CSF) 和脑组织钠水平在偏头痛期间增加。然而，关于偏头痛发作和传播期间大脑中钠稳态紊乱的潜在机制知之甚少。探索大脑中钠失调的原因很重要，因为纠正改变的钠稳态可能会治疗偏头痛。假设血脑脊液屏障 (BCSFB) 和/或血脑屏障 (BBB) 的钠转运机制紊乱是偏头痛期间脑脊液和脑组织钠水平升高的根本原因，我们开发了一种机制，大鼠大脑的微分方程模型，以比较 BCSFB 和 BBB 在控制 CSF 和脑组织钠水平方面的意义。该模型包括心室系统，蛛网膜下腔、脑组织和血液。钠从血液穿过 BCSFB 到 CSF 和从血液到脑组织穿过 BCSF 的转运分别由流入渗透系数 PBCSFB 和 PBBB 建模，而钠从 CSF 穿过 BCSFB 进入血液，从脑组织穿过 BCSFB 进入血液。 BBB 分别由外排渗透系数 PBCSFB' 和 PBBB' 建模。然后，我们进行了全局敏感性分析，以研究心室 CSF、蛛网膜下腔 CSF 和脑组织钠浓度对 PBCSFB、PBBB、PBCSFB' 和 PBBB' 病理生理变化的敏感性。我们的结果表明，心室脑脊液钠浓度受 PBCSFB 扰动的影响很大，而受 PBCSFB' 扰动的影响程度要小得多。在扰动开始的 30 分钟内，脑组织和蛛网膜下腔 CSF 钠浓度对 PBBB 和 PBBB' 的病理生理变化比 PBCSFB 和 PBCSFB' 的变化更敏感。然而，PBCSFB 是最敏感的模型参数，其次是 PBBB 和 PBBB'，用于控制扰动开始后 3 小时内的脑组织和蛛网膜下腔脑脊液钠水平。