Behav Brain Res. 2008 Dec 30. [Epub ahead of print]
Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long-Evans rat: Further development of a rodent model of autism.
Shultz SR, Macfabe DF, Martin S, Jackson J, Taylor R, Boon F, Ossenkopp KP, Cain DP.
Propionic acid (PPA) is a dietary short chain fatty acid and a metabolic end-product of enteric bacteria. Intracerebroventricular (ICV) injections of PPA can result in brain and behavioral abnormalities in rats similar to those seen in humans suffering from autism. To evaluate cognition and sensorimotor ability in the PPA model, male Long-Evans hooded rats received ICV injection of PPA or control compounds prior to behavioral testing in water maze and beam tasks. Compared to controls, PPA-treated rats were impaired in the water maze task as indicated by an unusual pattern of mild or no impairment during spatial acquisition training, but marked impairment during spatial reversal training. PPA-treated rats were also impaired on the beam task. Neuropathological analysis from PPA-treated rats revealed an innate neuroinflammatory response. These findings add to evidence that PPA can change the brain and behavior in the laboratory rat consistent with symptoms of human autism.
J Toxicol Environ Health B Crit Rev. 2008 Oct;11(8):660-80.
Potential for early-life immune insult including developmental immunotoxicity in autism and autism spectrum disorders: focus on critical windows of immune vulnerability.
Dietert RR, Dietert JM.
Early-life immune insults (ELII) including xenobiotic-induced developmental immunotoxicity (DIT) are important factors in childhood and adult chronic diseases. However, prenatal and perinatal environmentally induced immune alterations have yet to be considered in depth in the context of autism and autism spectrum disorders (ASDs). Numerous factors produce early-life-induced immune dysfunction in offspring, including exposure to xenobiotics, maternal infections, and other prenatal-neonatal stressors. Early life sensitivity to ELII, including DIT, results from the heightened vulnerability of the developing immune system to disruption and the serious nature of the adverse outcomes arising after disruption of one-time immune maturational events. The resulting health risks extend beyond infectious diseases, cancer, allergy, and autoimmunity to include pathologies of the neurological, reproductive, and endocrine systems. Because these changes may include misregulation of resident inflammatory myelomonocytic cells in tissues such as the brain, they are a potential concern in cases of prenatal-neonatal brain pathologies and neurobehavioral deficits. Autism and ASDs are chronic developmental neurobehavioral disorders that are on the rise in the United States [SO ARE TICK-BORNE INFECTIONS LIKE LYME DISEASE, BARTONELLA, BABESIA AND OTHER INFECTIONS—MOST CROSS THE PLACENTA] with prenatal and perinatal environmental factors suspected as contributors to this increase. Evidence for an association between environmentally associated childhood immune dysfunction and ASDs suggests that ELII and DIT may contribute to these conditions. However, it is not known if this linkage is directly associated with the brain pathologies or represents a separate (or secondary) outcome. This review considers the known features of ELII and DIT and how they may provide important clues to prenatal brain inflammation and the risk of autism and ASDs.
World J Biol Psychiatry. 2002 Jul;3(3):162-6.
Treatment of late onset autism as a consequence of probable autommune processes related to chronic bacterial infection.
Matarazzo EB.
Two cases are described of children who at first developed normally, but before the age of three developed autistic symptoms following the reactivation of a chronic oto-rhinolaryngologic infection. The clinical and laboratory data of the cases support the aetiological hypothesis of an autoimmune process. Adrenocorticotrophic hormone (ACTH), prescribed in the first months of the disease, cured one case. The other patient, who was two years old when autistic symptoms appeared and was treated only six years later, showed a partial but definitive improvement with the immunosuppressive treatment. This report proposes that reactivation of a chronic bacterial infection be included among the aetiologies of Late Onset Autism, and demonstrates that, when the aetiological hypothesis of an autoimmune process based on clinical and laboratory data is considered, an immunosuppressive treatment, particularly with ACTH, can be very effective and also safe.
Med Hypotheses. 2008;70(3):508-11. Epub 2007 Sep 29.
Therapy and epidemiology of autism--clostridial spores as key elements.
Finegold SM.
This manuscript reviews evidence indicating that intestinal bacteria, specifically clostridia, may play a role in certain cases of autism and hypothesizes that the clostridial spores (which are notably resistant to antimicrobial agents and commonly used germicides) are involved in: (1) relapse in the autistic subject after a response to an agent such as oral vancomycin, after the drug is discontinued, (2) the unexplained increased incidence of autism in recent years, and (3) the unexplained increase in numbers of multiple cases in the same family. Hypothesis (1), if established as valid, would spur research to find well-tolerated and safe agents that could be given together with vancomycin (or other appropriate antimicrobial agent) to eliminate spores; this would revolutionize the therapeutic approach. Hypotheses (2) and (3) relate to widespread use of antimicrobial agents, poor hygiene in young autistic children, and difficulty in removing spores from the home environment. These latter two hypotheses have major implications with regard to the epidemiology of this important and distressing disease and would encourage research into methods to eliminate clostridial spores from the home and other environments.
PMID: 17904761 [PubMed - indexed for MEDLINE]
Some But Not All Viruses Increase Autism
Arch Dis Child. 2008 Oct;93(10):832-7. Epub 2008 Feb 5.
Measles vaccination and antibody response in autism spectrum disorders.
Baird G, Pickles A, Simonoff E, Charman T, Sullivan P, Chandler S, Loucas T, Meldrum D, Afzal M, Thomas B, Jin L, Brown D.
OBJECTIVE: To test the hypothesis that measles vaccination was involved in the pathogenesis of autism spectrum disorders (ASD) as evidenced by signs of a persistent measles infection or abnormally persistent immune response shown by circulating measles virus or raised antibody titres in children with ASD who had been vaccinated against measles, mumps and rubella (MMR) compared with controls. DESIGN: Case-control study, community based. METHODS: A community sample of vaccinated children aged 10-12 years in the UK with ASD (n = 98) and two control groups of similar age, one with special educational needs but no ASD (n = 52) and one typically developing group (n = 90), were tested for measles virus and antibody response to measles in the serum. RESULTS: No difference was found between cases and controls for measles antibody response. There was no dose-response relationship between autism symptoms and antibody concentrations. Measles virus nucleic acid was amplified by reverse transcriptase-PCR in peripheral blood mononuclear cells from one patient with autism and two typically developing children. There was no evidence of a differential response to measles virus or the measles component of the MMR in children with ASD, with or without regression, and controls who had either one or two doses of MMR. Only one child from the control group had clinical symptoms of possible enterocolitis. CONCLUSION: No association between measles vaccination and ASD was shown. [Of course some parents and practitioners in the progressive camp reject this result. But all agree not all viruses cause autism, which is my only point here].
Final Thoughts
The causes of neuron injury in the womb and after birth are many. Autism spectrum disorder children are not helped by limited explorations, limited looks at causes or the rejection of options outside the rigid world of political medicine. Progressive physicians often also are just as rigid in etiology and treatments, and only use treatments that have been around for over 20 years with only limited benefit.