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A Possible Central Mechanism in Autism Spectrum Disorders: Interaction of Activated Microglia, Excitotoxicity, Reactive Oxygen and Nitrogen Species, Lipid Peroxidation Products and the Role of Elevated Androgen Levels in Autism Spectrum Disorders
by Russell L. Blaylock, MD
374 research studies cited
The autism spectrum disorders are a group of related neurodevelopmental disorders, which have been increasing in incidence since the 1980s. While a large mass of information and data has been forthcoming, still a central unifying mechanism has not been offered. A review of the studies on autism spectrum disorders disclose a number of findings that are interconnected.
Most important appears to be disruption of brain cell calcium homeostasis by a number of events, such as excitotoxicity, androgen excess and elevations in inflammatory cytokines. Free radical generation and lipid peroxidation is a common event in examined cases of autism spectrum disorder. Recently, researchers have discovered high levels of androgens in a group of autistic children and that pharmaceutical lowering of androgen levels can produce rapid and dramatic improvement in a number of cases. Several studies have shown worsening of neurological injuries under conditions of high androgen levels. In addition, high androgen levels have been shown to trigger calcium accumulation in neurons through a special membrane receptor.
Likewise, a number of researchers have found rapid improvement in symptoms following anti-inflammatory treatments or dietary changes. What all these events have in common is that they magnify the excitotoxic process, a major mechanism for CNS injury due to a number of insults, including hypoxia/ischemia, heavy metal poisoning, trauma, infections, seizures and hypoglycemia. Many have noted an association between an increase in the number of vaccines added to the immunization schedule coincident with the rise in autism cases. An abundance of research has shown that systemic immune activation can trigger brain microglial activation, the resident immune cell type for the central nervous system (CNS). It has also been shown, that when these microglia are primed by prior stimulation, the intensity of the immune reaction is greatly magnified. Subsequent immune stimulation turns this into a chronic state of activation.
Others have noted the connection to high mercury burdens in the autistic child secondary to mercury containing vaccines (thimerosal) and from other sources. Mercury is a powerful activator of microglia, even in very minute doses. In addition, mercury inhibits a number of energy-generating enzymes systems, triggers free radical generation and lipid peroxidation, inhibits a number of antioxidant systems and inhibits the glutamate transport proteins, also at very low concentrations.
There is compelling evidence that excessive immune stimulation during critical stages of brain development can cause disruption of neurodevelopment by affecting neuronal and glial cell migration, dendritic outgrowth, synaptic development and consolidation and by triggering neurodegeneration.
Because the majority of the vaccinations are given during the period of most rapid brain growth, such hyperimmune brain activation risk disrupting neurodevelopment, especially for higher cortical functions. This has been repeatedly shown in experimental animals. Intimately connected with CNS microglial activation is the release of powerful excitotoxins, glutamate and quniolinic acid. This is especially so since glutamate plays a critical role in brain cell migration, differentiation, synaptic stabilization and pruning. The level of glutamate, which fluctuate throughout neurodevelopment, is critical. Here I show that altering these levels by way of immune alterations and other mechanisms, plays havoc on the developing nervous system.