Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts

Jacob C. Zbesko, Thuy Vi V. Nguyen, Tao Yang, Jennifer Beischel Frye, Omar Hussain, Megan Hayes, Amanda Chung, W. Anthony Day, Kristina Stepanovic, Maj Krumberger, Justine Mona, Frank M. Longo, Kristian P. Doyle

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)63-78
Number of pages16
JournalNeurobiology of Disease
StatePublished - Apr 2018


  • Chronic stroke
  • Glial scar
  • Inflammation
  • Liquefactive necrosis
  • Neurodegeneration

ASJC Scopus subject areas

  • Neurology


Dive into the research topics of 'Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts'. Together they form a unique fingerprint.

Cite this