Biological Functions of Extravasated Serum IgG in Rat Brain

Kadota, Eiji; Muramatsu, Yusuke; Nonaka, Kiyoko; Karasuno, M.; Nishi, Katsuhide; Dote, Kunio; Hashimoto, Shigeo

doi:10.1007/978-3-7091-6346-7_14

Cited by 14 publications

(6 citation statements)

References 5 publications

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“…Increases in BBB permeability permit the entry of blood‐borne xenobiotics and endogenous molecules into the brain, disturbing CNS homeostasis and promoting neuronal dysfunction and death. For example, serum albumin is capable of inducing degeneration of cholinergic neurons (Moser and Humpel 2007), while serum IgG is known to initiate neutorphil infiltration and associated immune response in the brain (Kadota et al. 2000).…”

Section: Discussionmentioning

confidence: 99%

Soluble aggregates of the amyloid‐β protein selectively stimulate permeability in human brain microvascular endothelial monolayers

Gonzalez-Velasquez

Kotarek

Moss

2008

Journal of Neurochemistry

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Cerebral amyloid angiopathy associated with Alzheimer’s disease is characterized by cerebrovascular deposition of the amyloid-β protein (Aβ). Aβ elicits a number of morphological and biochemical alterations in the cerebral microvasculature, which culminate in hemorrhagic stroke. Among these changes, compromise of the blood-brain barrier has been described in Alzheimer’s disease brain, transgenic animal models of Alzheimer’s disease, and cell culture experiments. In the current study, presented data illustrates that isolated soluble Aβ1-40 aggregates, but not unaggregated monomer or mature fibril, enhance permeability in human brain microvascular endothelial monolayers. Aβ1-40-induced changes in permeability are paralleled by both a decrease in transendothelial electrical resistance and a re-localization of the tight junction associated protein zonula occludin-1 away from cell borders and into the cytoplasm. Small soluble Aβ1-40 aggregates are confirmed to be the most potent stimulators of endothelial monolayer permeability by establishing an inverse relationship between average aggregate size and stimulated changes in diffusional permeability coefficients. These results support previous findings demonstrating that small soluble Aβ1-40 aggregates are also primarily responsible for endothelial activation, suggesting that these same species may elicit other changes in the cerebrovasculature associated with cerebral amyloid angiopathy and Alzheimer’s disease.

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Section: Discussionmentioning

confidence: 99%

Soluble aggregates of the amyloid‐β protein selectively stimulate permeability in human brain microvascular endothelial monolayers

Gonzalez-Velasquez

Kotarek

Moss

2008

Journal of Neurochemistry

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“…Although there are numerous examples supporting a monoclonal antibody‐induced central nervous system effect,26–28 interparenchymally infused IgG may not necessarily be neurotoxic. For example, the intracortical injection of purified IgG into rodent cortex caused infiltration of neutrophils and cytokine changes in microglia and endothelium but no neuronal damage 29. It is also widely accepted that healthy individuals have serum antibodies directed against neuronal tissues that are generally considered to be largely nonspecific and of little physiological importance 30–35…”

Section: Discussionmentioning

confidence: 99%

Striatal microinfusion of Tourette syndrome and PANDAS sera: Failure to induce behavioral changes

et al. 2003

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Rodent striatal microinfusions have been suggested as a model for assessing the behavioral effects induced by antineuronal antibodies. We used this approach to evaluate the proposed autoimmune etiology for Tourette syndrome (TS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Sera were assessed from patients with TS (n = 9) preselected based on the presence of elevated enzyme-linked immunosorbent assay optical densities against putamen homogenate and sera from patients with PANDAS (n = 8), selected from a larger group assayed for antibodies against a putamen synaptosomal preparation. The effect of antibodies against the streptococcal M5 protein were also studied. A total of 44 Fischer rats received bilateral infusion of sera: 23 ventral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 8 control); 21 ventrolateral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 6 controls). Cannulas were placed bilaterally and symmetrically by stereotactic techniques. After animals were allowed to recover for 1 week, sera were microinfused for 3 days. Animal behavior was then simultaneously quantified by daily observation and monitoring using automated activity boxes for 10 days after infusion. No significant alterations in stereotypic behavior or movement were observed between the PANDAS, TS, or anti-M5 protein and control groups. Our findings are in contrast to previous reports, and suggest the need for further investigations to determine the validity of the model and of autoimmune-mediated hypotheses for pediatric movement disorders.

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“…Cell debris, cytokines and serum components gaining access to the brain through a damaged blood-brain barrier have been implicated as microglial activators (Chamak and Mallat, 1991;Lassmann et al, 1991;Benveniste, 1992;Nakajima and Kohsaka, 2001;Kadota et al, 2000;Lu et al, 2001). The microglial response comprises reactive morphological changes as well as changes in their functional properties, including proliferation, phagocytosis, migration and release of cytokines (Thomas, 1992;Perry et al, 1995;Gehrmann and Kreutzberg, 1995;Giulian, 1995).…”

Section: Introduction Mmentioning

confidence: 99%

Time Course of Proliferation and Elimination of Microglia/Macrophages in Different Neurodegenerative Conditions

Vela

Yáñez

González

et al. 2002

Journal of Neurotrauma

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Ablation of the hindlimb area of the sensorimotor cortex produces degeneration in the cortex (invasive traumatic injury) and leads to retrograde and/or anterograde degeneration in the thalamus (non-invasive injury, distal reaction). This provides an useful model to study the proliferation and elimination of microglia/macrophages in different neurodegenerative conditions. Changes in the morphology, distribution and numbers of microglia in the affected cortex and thalamus were analyzed at various time points (12 h to 30 days) after injury. In parallel, proliferation was determined by immunocytochemistry for the proliferating cell nuclear antigen and cell death by the TUNEL method. Proliferation was an early event in the microglia/macrophage response (from 12 h in the cortex and from 2 days post-lesion in the thalamus) and persisted up to 30 days. The different microglia/macrophage phenotypes proliferated in a specific temporospatial pattern. In the lesioned cortex, early activation and proliferation of intrinsic microglia was accompanied, from the second post-lesion day, by monocyte entrance and proliferation of monocyte-derived cells. In contrast, accumulation of cells in the thalamus resulted from proliferation of intrinsic microglia, without apparent/significant monocytic recruitment. During the subsequent microglia/macrophages removal the majority of the cells in the cortex transformed into ameboid cells devoid of cell processes that progressively accumulated as fully-developed macrophages tissue within the lesion (3-14 days) ultimately migrating out to the meningeal connective tissue (14-30 days). Only some process-bearing cells, remaining in the cortical tissue bordering the lesion, underwent degeneration by 14-21 days post-lesion. In contrast, in the distal affected thalamic nuclei, microglial cell death occurred by 14-30 days post-lesion. Altogether, this study shows that both the origin and fate of microglia/ macrophages depend on the nature of the lesion.

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Biological Functions of Extravasated Serum IgG in Rat Brain

Cited by 14 publications

References 5 publications

Soluble aggregates of the amyloid‐β protein selectively stimulate permeability in human brain microvascular endothelial monolayers

Soluble aggregates of the amyloid‐β protein selectively stimulate permeability in human brain microvascular endothelial monolayers

Striatal microinfusion of Tourette syndrome and PANDAS sera: Failure to induce behavioral changes

Time Course of Proliferation and Elimination of Microglia/Macrophages in Different Neurodegenerative Conditions

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