Excerpt:
“In summary, NF-κB is aberrantly expressed in orbitofrontal cortex in patients with ASC, as part of a putative molecular cascade leading to inflammation, especially of resident immune cells in brain regions associated with the behavioral and clinical symptoms of ASC.”
Excerpt:
“Therefore, autism is the result of genetic defects and/or inflammation of the brain. The inflammation could be caused by a defective placenta, immature blood-brain barrier, the immune response of the mother to infection while pregnant, a premature birth, encephalitis in the child after birth, or a toxic environment.”
Conclusions: HgCl2 stimulates VEGF and IL-6 release from human mast cells. This phenomenon could disrupt the blood-brain-barrier and permit brain inflammation. As a result, the findings of the present study provide a biological mechanism for how low levels of mercury may contribute to ASD pathogenesis.
Excerpts:
“Measles might be etiologically linked to autism because measles and MMR antibodies (a viral marker) correlated positively to brain autoantibodies (an autoimmune marker)–salient features that characterize autoimmune pathology in autism.”
“Conclusions: The scientific evidence is quite credible for our autoimmune hypothesis, leading to the identification of autoimmune autistic disorder (AAD) as a major subset of autism.”
Excerpt:
“In autism, over-zealous neuroinflammatory responses could not only influence neural developmental processes, but may more significantly impair neural signaling involved in cognition in an ongoing fashion.”
Excerpt:
“Elevation of cerebrospinal fluid levels of tumor necrosis factor-alpha was significantly higher (mean = 104.10 pg/mL) than concurrent serum levels (mean = 2.78 pg/mL) in all of the patients studied. The ratio of the cerebrospinal fluid levels to serum levels averaged 53.7:1. This ratio is significantly higher than the elevations reported for other pathological states for which cerebrospinal fluid and serum tumor necrosis factor-alpha levels have been simultaneously measured.”
Abstract
Autism is defined behaviorally, as a syndrome of abnormalities involving language, social reciprocity and hyperfocus or reduced behavioral flexibility. It is clearly heterogeneous, and it can be accompanied by unusual talents as well as by impairments, but its underlying biological and genetic basis in unknown. Autism has been modeled as a brain-based, strongly genetic disorder, but emerging findings and hypotheses support a broader model of the condition as a genetically influenced and systemic. These include imaging, neuropathology and psychological evidence of pervasive (and not just specific) brain and phenotypic features; postnatal evolution and chronic persistence of brain, behavior and tissue changes (e.g. inflammation) and physical illness symptomatology (e.g. gastrointestinal, immune, recurrent infection); overlap with other disorders; and reports of rate increases and improvement or recovery that support a role for modulation of the condition by environmental factors (e.g. exacerbation or triggering by toxins, infectious agents, or others stressors, or improvement by treatment). Modeling autism more broadly encompasses previous work, but also encourages the expansion of research and treatment to include intermediary domains of molecular and cellular mechanisms, as well as chronic tissue, metabolic and somatic changes previously addressed only to a limited degree. The heterogeneous biologies underlying autism may conceivably converge onto the autism profile via multiple mechanisms on the one hand and processing and connectivity abnormalities on the other may illuminate relevant final common pathways and contribute to focusing on the search for treatment targets in this biologically and etiologically heterogeneous behavioral syndrome.
Excerpt: “Upon completion of this article, participants should be able to: 1. Be aware of laboratory and clinical evidence of greater oxidative stress in autism. 2. Understand how gut, brain, nutritional, and toxic status in autism are consistent with greater oxidative stress. 3. Describe how anti-oxidant nutrients are used in the contemporary treatment of autism.”
Excerpt:
“The promoters of genes up-regulated by aluminum are enriched in binding sites for the stress-inducible transcription factors HIF-1 and NF-kappaB, suggesting a role for aluminum, HIF-1 and NF-kappaB in driving atypical, pro-inflammatory and pro-apoptotic gene expression. The effect of aluminum on specific stress-related gene expression patterns in human brain cells clearly warrant further investigation.”
Excerpt: “Because this neuroinflammatory process appears to be associated with an ongoing and chronic mechanism of CNS dysfunction, potential therapeutic interventions should focus on the control of its detrimental effects and thereby eventually modify the clinical course of autism.”
