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Surg Neurol Int. 2018 Apr 9;9:74. doi: 10.4103/sni.sni_407_17. eCollection 2018.

Immunoexcitotoxicity as the central mechanism of etiopathology and treatment of autism spectrum disorders: A possible role of fluoride and aluminum.

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Institute of Medical Biochemistry, Laboratory of Neuropharmacology, 1 Faculty of Medicine, Charles University in Prague, Praque, Czech Republic.
Theoretical Neurosciences Research, LLC, Ridgeland, Mississippi, USA.
Faculty of Health and Social Studies, Institute of Radiology, Toxicology and Civil Protection, University of South Bohemia Ceske Budejovice, Branisovska, Czech Republic.
Laboratory of Applied Hydrobiology, University of South Bohemia, Husova tř. 458/102, 370 05 České Budějovice, Czech Republic.


Our review suggests that most autism spectrum disorder (ASD) risk factors are connected, either directly or indirectly, to immunoexcitotoxicity. Chronic brain inflammation is known to enhance the sensitivity of glutamate receptors and interfere with glutamate removal from the extraneuronal space, where it can trigger excitotoxicity over a prolonged period. Neuroscience studies have clearly shown that sequential systemic immune stimulation can activate the brain's immune system, microglia, and astrocytes, and that with initial immune stimulation, there occurs CNS microglial priming. Children are exposed to such sequential immune stimulation via a growing number of environmental excitotoxins, vaccines, and persistent viral infections. We demonstrate that fluoride and aluminum (Al3+) can exacerbate the pathological problems by worsening excitotoxicity and inflammation. While Al3+ appears among the key suspicious factors of ASD, fluoride is rarely recognized as a causative culprit. A long-term burden of these ubiquitous toxins has several health effects with a striking resemblance to the symptoms of ASD. In addition, their synergistic action in molecules of aluminofluoride complexes can affect cell signaling, neurodevelopment, and CNS functions at several times lower concentrations than either Al3+ or fluoride acting alone. Our review opens the door to a number of new treatment modes that naturally reduce excitotoxicity and microglial priming.


Aluminofluoride complexes; aluminum; autism spectrum disorders; cytokines; fluoride; glutamatergic neurotransmission; immunoexcitotoxicity; microglial activation; neurodevelopment

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