Strunecka Anna, Blaylock Russell L, Patocka Jiri, Strunecky Otakar
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.
Surg Neurol Int. 2018 Apr 9;9:74. doi: 10.4103/sni.sni_407_17. eCollection 2018.
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 (Al) can exacerbate the pathological problems by worsening excitotoxicity and inflammation. While Al 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 Al or fluoride acting alone. Our review opens the door to a number of new treatment modes that naturally reduce excitotoxicity and microglial priming.
我们的综述表明，大多数自闭症谱系障碍（ASD）风险因素直接或间接地与免疫兴奋性毒性有关。已知慢性脑部炎症会增强谷氨酸受体的敏感性，并干扰从神经元外间隙清除谷氨酸，在该间隙谷氨酸可长期引发兴奋性毒性。神经科学研究清楚地表明，序贯性全身免疫刺激可激活大脑的免疫系统、小胶质细胞和星形胶质细胞，并且在初次免疫刺激时，会发生中枢神经系统小胶质细胞致敏。儿童通过越来越多的环境兴奋性毒素、疫苗和持续性病毒感染接触到这种序贯性免疫刺激。我们证明，氟化物和铝（Al）可通过加剧兴奋性毒性和炎症来加重病理问题。虽然铝似乎是自闭症谱系障碍的关键可疑因素之一，但氟化物很少被认为是致病元凶。这些普遍存在的毒素的长期负担会产生多种健康影响，与自闭症谱系障碍的症状极为相似。此外，它们在铝氟络合物分子中的协同作用，能够在比单独的铝或氟化物低几倍的浓度下影响细胞信号传导、神经发育和中枢神经系统功能。我们的综述为一些自然降低兴奋性毒性和小胶质细胞致敏的新治疗模式打开了大门。
