Regulation of CSF and Brain Tissue Sodium Levels by the Blood-CSF and Blood-Brain Barriers During Migraine

Abstract

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 P BCSFB and P BBB , 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 P ′ BCSFB and P ′ BBB , 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 P BCSFB , P BBB , P ′ BCSFB and P ′ BBB . Our results show that the ventricular CSF sodium concentration is highly influenced by perturbations of P BCSFB , and to a much lesser extent by perturbations of P ′ BCSFB . Brain tissue and subarachnoid CSF sodium concentrations are more sensitive to pathophysiological variations of P BBB and P ′ BBB than variations of P BCSFB and P ′ BCSFB within 30 min of the onset of the perturbations. However, P BCSFB is the most sensitive model parameter, followed by P BBB and P ′ BBB , in controlling brain tissue and subarachnoid CSF sodium levels within 3 h of the perturbation onset.

Neuroimaging of Cerebral Blood Flow and Sodium in Women with Lipedema

“…Active transport at the blood-CSF and blood-brain barriers could mitigate excess sodium, despite accumulation in other tissues. For instance, computer models of barrier permeability demonstrated the ability to clear acute temporal elevation in brain and CSF sodium before and after migraine onset (46). Although the mean brain TSC at one time point was not different in this study of patients with lipedema, improved temporal resolution of 23 Na MRI would be warranted to better characterize brain sodium regulation in diseases of pain such as lipedema.…”

Sodium Chloride, Migraine and Salt Withdrawal: Controversy and Insights

“…An early experiment testing the consumption of large amounts of water found that urinary sodium excretion was higher in patients with migraine compared to normal participants [ 21 ], suggesting higher concentrations of sodium in migraine patients. Additionally, sodium permeability through the blood–brain barrier and blood–cerebrospinal fluid barrier increases during migraine [ 22 ].…”

Sodium Toxicity in the Nutritional Epidemiology and Nutritional Immunology of COVID-19

“…Incidentally, the coronavirus discovered in Wuhan, China, in December 2019 was first detected in cases of novel coronavirus-infected pneumonia (NCIP) [ 79 ]. Likewise, high sodium chloride intake and sodium concentration levels are risk factors associated with stroke [ 80 ], thrombosis [ 81 ], cardiac arrhythmias [ 82 , 83 ], obesity [ 84 ], diabetes [ 85 ], kidney disease [ 86 ], hepatic disease [ 87 ], multiple sclerosis [ 88 ], systemic sclerosis [ 89 ], migraine [ 90 ], tinnitus [ 91 ], Bell’s palsy [ 92 ], polycystic ovary syndrome [ 93 ], and pneumonia [ 94 ], providing clinical evidence that these diseases form a transitive link between COVID-19 and a high sodium chloride intake. Transitive inference is a comparative analysis tool described in the present author’s previous work [ 16 ].…”

“…The edema of the nasal mucosal is a clinical feature of acute rhinosinusitis or inflammation of the nasal sinus mucosa, which is claimed to be caused by viruses [ 178 ]. The association of viral infections with rhinosinusitis may be mediated by sodium-induced hypervolemia and nasal mucosal edema, which could explain why nasal congestion and headache is associated with SARS-CoV-2 infection under conditions of sodium toxicity [ 90 , 179 , 180 , 181 , 182 ].…”

“…Migraine is associated with COVID-19 [ 74 ]. Researchers have demonstrated increased sodium permeability through the blood−brain barrier and blood cerebral spinal fluid barrier during migraine [ 90 ], and future research should investigate an association between this mechanism and sodium dietary intake. Dysregulated voltage-gated sodium channels are proposed to increase neurovascular compression on the roots of trigeminal cranial nerve fibers and cause migraine pain [ 179 ], and an association between this dysregulated mechanism with dietary sodium intake should also be investigated.…”