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Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts.
Zbesko, Jacob C; Nguyen, Thuy-Vi V; Yang, Tao; Frye, Jennifer Beischel; Hussain, Omar; Hayes, Megan; Chung, Amanda; Day, W Anthony; Stepanovic, Kristina; Krumberger, Maj; Mona, Justine; Longo, Frank M; Doyle, Kristian P.
Afiliación
  • Zbesko JC; Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
  • Nguyen TV; Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA; Department of Neurology, University of Arizona, Tucson, AZ 85719, USA.
  • Yang T; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Frye JB; Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
  • Hussain O; Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
  • Hayes M; Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
  • Chung A; Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
  • Day WA; Arizona Health Sciences Center Imaging Core Facility, Arizona Research Labs, University of Arizona, Tucson, AZ 85719, USA.
  • Stepanovic K; Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
  • Krumberger M; Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
  • Mona J; Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
  • Longo FM; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Doyle KP; Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA; Department of Neurology, University of Arizona, Tucson, AZ 85719, USA; Arizona Center on Aging, University of Arizona, Tucson, AZ 85719, USA. Electronic address: doylekr@email.arizona.edu.
Neurobiol Dis ; 112: 63-78, 2018 04.
Article en En | MEDLINE | ID: mdl-29331263
Following stroke, the damaged tissue undergoes liquefactive necrosis, a stage of infarct resolution that lasts for months although the exact length of time is currently unknown. One method of repair involves reactive astrocytes and microglia forming a glial scar to compartmentalize the area of liquefactive necrosis from the rest of the brain. The formation of the glial scar is a critical component of the healing response to stroke, as well as other central nervous system (CNS) injuries. The goal of this study was to evaluate the toxicity of the extracellular fluid present in areas of liquefactive necrosis and determine how effectively it is segregated from the remainder of the brain. To accomplish this goal, we used a mouse model of stroke in conjunction with an extracellular fluid toxicity assay, fluorescent and electron microscopy, immunostaining, tracer injections into the infarct, and multiplex immunoassays. We confirmed that the extracellular fluid present in areas of liquefactive necrosis following stroke is toxic to primary cortical and hippocampal neurons for at least 7 weeks following stroke, and discovered that although glial scars are robust physical and endocytic barriers, they are nevertheless permeable. We found that molecules present in the area of liquefactive necrosis can leak across the glial scar and are removed by a combination of paravascular clearance and microglial endocytosis in the adjacent tissue. Despite these mechanisms, there is delayed atrophy, cytotoxic edema, and neuron loss in regions adjacent to the infarct for weeks following stroke. These findings suggest that one mechanism of neurodegeneration following stroke is the failure of glial scars to impermeably segregate areas of liquefactive necrosis from surviving brain tissue.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infarto Cerebral / Neuroglía / Cicatriz / Accidente Cerebrovascular / Gliosis Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Neurobiol Dis Asunto de la revista: NEUROLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infarto Cerebral / Neuroglía / Cicatriz / Accidente Cerebrovascular / Gliosis Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Neurobiol Dis Asunto de la revista: NEUROLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos