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Articles by Sandra L. Siedlak
Total Records ( 2 ) for Sandra L. Siedlak
  Teresa A. Evans , Sandra L. Siedlak , Liang Lu , Xiaoming Fu , Zeneng Wang , Woody R. McGinnis , Evelyn Fakhoury , Rudy J. Castellani , Stanley L. Hazen , William J. Walsh , Allen T. Lewis , Robert G. Salomon , Mark A. Smith , George Perry and Xiongwei Zhu
  Oxidative damage has been documented in the peripheral tissues of autism patients. In this study, we sought evidence of oxidative injury in autistic brain. Carboxyethyl pyrrole (CEP) and iso[4]levuglandin (iso[4]LG)E2-protein adducts, that are uniquely generated through peroxidation of docosahexaenoate and arachidonate-containing lipids respectively, and heme oxygenase-1 were detected immunocytochemically in cortical brain tissues and by ELISA in blood plasma. Significant immunoreactivity toward all three of these markers of oxidative damage in the white matter and often extending well into the grey matter of axons was found in every case of autism examined. This striking threadlike pattern appears to be a hallmark of the autistic brain as it was not seen in any control brain, young or aged, used as controls for the oxidative assays. Western blot and immunoprecipitation analysis confirmed neurofilament heavy chain to be a major target of CEP-modification. In contrast, in plasma from 27 autism spectrum disorder patients and 11 age-matched healthy controls we found similar levels of plasma CEP (124.5 ± 57.9 versus 110.4 ± 30.3 pmol/mL), iso[4]LGE2 protein adducts (16.7 ± 5.8 versus 13.4 ± 3.4 nmol/mL), anti-CEP (1.2 ± 0.7 versus 1.2 ± 0.3) and anti-iso[4]LGE2 autoantibody titre (1.3 ± 1.6 versus 1.0 ± 0.9), and no differences between the ratio of NO2Tyr/Tyr (7.81 E-06 ± 3.29 E-06 versus 7.87 E-06 ± 1.62 E-06). These findings provide the first direct evidence of increased oxidative stress in the autistic brain. It seems likely that oxidative injury of proteins in the brain would be associated with neurological abnormalities and provide a cellular basis at the root of autism spectrum disorders.
  David J. Bonda , Kate M. Webber , Sandra L. Siedlak , George Perry , Robert P. Friedland and Mark A. Smith
  The mechanism(s) responsible for the loss of neurons that characterizes Alzheimer disease is incompletely understood. Nonetheless, there is considerable evidence suggestive of immune abnormalities coupled to alterations in blood-brain barrier permeability that likely play a key role in both the etiology and progression of the disease. To examine these issues further, this study was designed to examine the presence of human antibodies within hippocampal regions of both diseased and normal brains. Specifically, using antibodies directed against either human lambda (λ) or kappa (κ) subunits of human IgG, we examined the amount and localization of endogenous human antibodies within the brain. In cases of Alzheimer disease, but not in age-matched controls, we found human antibodies associated with pyramidal neurons and dystrophic neurites surrounding amyloid plaques - pathological structures that characterize the disease. Since such human immunoglobulins likely originate in the vasculature, we also examined cases of cerebral amyloid angiopathy to further explore the importance of blood-brain barrier breaches and found high levels of antibodies associated with many blood vessels as well as pyramidal neurons. Taken together, these findings strengthen the notion that alterations in blood brain barrier permeability in both Alzheimer disease and cerebral amyloid angiopathy leads to the accumulation of antibodies that then may contribute to the inflammatory cascade within the brain.
 
 
 
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