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Endothelial cells line the inside of blood vessels from the aorta to microvessels, and form a selective blood-tissue barrier that protects every organ system. Fluoride and Endothelial Cell Dysfunction The Dangers of Sevoflurane, an Inhaled General Anesthetic A major cause of vascular dementia is small vessel disease (SVD), which also triples the risk of stroke and contributes to Alzheimer's disease. A study published in July 2018 shows that endothelial cell dysfunction in the blood-brain barrier (BBB) is the first pathological change in the development of SVD in older people.[1] A study cited found that the BBB is compromised after exposure to Sevoflurane, an inhaled general anesthetic that significantly increases blood fluoride levels. Sevoflurane flattens endothelial cells to increase BBB permeability.[2,3] Sevoflurane is associated with high rates of post-operative delirium, a common and often fatal disorder affecting as many as 50% of older people during surgery or hospitalization. The severity of post-operative delirium correlates directly to the severity of later cognitive impairment and decline.[4] ** Another drug that increases blood fluoride levels is 5-fluorouracil, which in 2017 was found to "cause endothelial cell senescence and dysfunction."[5,6] In 2001, it was "demonstrated that sodium fluoride causes dramatic endothelial cell barrier dysfunction."[7] In July 2018, researchers at the University of Exeter showed that key aspects of human cell aging can be reversed by decreasing levels of endothelial cells that are senescent (older cells that stop dividing).[8] A common mechanism in age-related diseases like dementia, cancer, and diabetes is the accumulation of these dysfunctional endothelial cells that are not just an effect of aging, said Professor Lorna Harries. "It's a reason why we age." Jan. 2020: Sevoflurane anesthesia is linked to breast cancer metastasis. [Li et al.] General anesthesia in cesarean deliveries increases odds of postpartum depression by 54%. Odds of suicidal thoughts or self-inflicting injury rise to 91%. [Columbia University] Endothelial dysfunction is involved in most major diseases whose costs and prevalence are detailed at End Fluoridation: Save $Billions. Endothelial dysfunction is one of fluoride's pathological processes documented at Mental Fluorosis. References 1. Barney J. Stabilizing endothelial cells could help tackle vascular dementia. American Association for the Advancement of Science. July 2018. 2. Acharya NK, Goldwaser EL, Forsberg MM, et al. Sevoflurane and isoflurane induce structural changes in brain vascular endothelial cells and increase blood-brain barrier permeability: Possible link to postoperative delirium and cognitive decline. Brain Res. 2015 Sep 16;1620:29-41. 3. Goldberg ME, Cantillo J, Larijani GE, et al. Sevoflurane versus isoflurane for maintenance of anesthesia: are serum inorganic fluoride ion concentrations of concern? Anesth Analg. 1996 Jun;82(6):1268-1272. 4. Howe C. Severity of post-operative delirium relates to severity of cognitive decline. Hebrew SeniorLife Institute for Aging Research. November 28, 2017. 4b https://pubmed.ncbi.nlm.nih.gov/25960348/ 5. Hull WE, Port RE, Herrmann R, et al. Metabolites of 5-fluorouracil in plasma and urine... Cancer Res. 1988 Mar 15;48(6):1680-1688. 6. Altieri P, Murialdo R, Barisione C, et al. 5-fluorouracil causes endothelial cell senescence: potential protective role of glucagon-like peptide 1. Br J Pharmacol. 2017 Nov;174(21):3713-3726. 7. Wang P, Verin AD, et al. Mechanisms of sodium fluoride-induced endothelial cell barrier dysfunction: role of MLC phosphorylation. Am J Physiol Lung Cell Mol Physiol. 2001 Dec;281(6):L1472-1483. 8. Key aspects of human cell aging reversed by new compounds. University of Exeter Medical School. August 7, 2018. 9. Musi N, Valentine JM, Sickora KR, et al. Tau protein aggregation is associated with cellular senescence in the brain. Aging Cell. 2018 Aug 20:e12840. An August 2018 study found a strong association between cellular senescence in the brain and the presence of tau-containing neurofibrillary tangles, whose accumulation is the most common pathology among degenerative brain diseases. Clearing even a small percentage of the senescent cells improves health span and delays age-associated diseases.[9] Meeme et al (2017) found that endothelial cell dysfunction is also a central mechanism in the pathophysiology of preeclampsia, the dangerous pregnancy complication explored in "Placental Fluorosis," Chapter 2 of the book. A marker of endothelial dysfunction is soluble Endoglin (sEng), whose levels are elevated in preeclampsia. Tskitishvili et al (2010) showed that amniotic tissue cultures treated with sodium fluoride have significantly higher expression levels of sEng. African American children are more vulnerable to fluoride's toxicity. They have significantly higher rates and more severe forms of dental fluorosis than either white or Hispanic children. A study of African American and white 7-14 years olds found that even though both groups had the same fluoride concentrations in their drinking water and saliva, dental fluorosis was 28% higher in African American children. – Connett (2012), Martinez-Mier (2010) Black Americans Have a Higher Prevalence of Cardiovascular Disease (CVD) "In this biracial community-based sample, we demonstrate that black race is associated with impaired vascular function compared with whites. Specifically, blacks had (1) reduced microvascular endothelial function measured as RHI; (2) abnormal arterial wave reflections, measured as higher PAT-AIx and CAIx; and (3) greater arterial stiffness, measured as higher PWV, even after adjustment for traditional CVD risk factors. Importantly, these differences were present even in the subgroup of participants who were completely free of conventional CVD risk factors." Morris AA, Patel RS, Binongo JN, et al. Racial differences in arterial stiffness and microcirculatory function between Black and White Americans. J Am Heart Assoc. 2013 Apr 8;2(2):e002154.