Presentation Title

Time Course of Ischemia and Cell Death in a Mouse Model of White Matter Stroke

Faculty Mentor

S. Thomas Carmichael

Start Date

17-11-2018 12:30 PM

End Date

17-11-2018 2:30 PM

Location

HARBESON 13

Session

POSTER 2

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

White matter stroke(WMS), constituting 15-25% of all stroke subtypes, is a progressive disease that often results in severe vascular disruption and cell death within infarct and peri-infarct regions. Although the impacts are devastating, the short and long-term pathological effects of ischemia in the white matter have not been fully explored yet due to the underdevelopment of animal models for research and treatments. Using an in vivo novel mouse model to induce subcortical WMS that similarly mimic the size and location of the disease in humans, we aim to assess the vasculature to determine endothelial fates and vascular repair at key time points, and characterize cellular apoptosis and recovery levels post-stroke. For this study, WMS is induced by stereotactically injecting a small molecule vasoconstrictor, N-iminoethyl-L-ornithine(L-NIO), along 3 sites of the corpus callosum to create a localized ischemia. After recovery, conjugated FITC-dextran is injected transcardially prior to sacrifice to label perfusing vessels and is co-stained with endothelial markers to determine vascular damage. Results from quantification of blood vessels show vascular impairments up to 15 days post-stroke, suggesting that the model is capable of creating not just transient ischemia but persistent vascular damages. Using combined methods terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) assay and immunohistochemistry, identified cell types experiencing apoptosis post-stroke primarily include oligodendrocytes, oligodendrocyte precursor cells(OPCs), and astrocytes. Preliminary cell quantification demonstrate correlation between cell death and recovery time points in astrocytes and oligodendrocytes; However, populations of OPCs continue to experience apoptotic death and proliferation in the same time period. Fate mapping OPCs using EdU assay further demonstrate their failure to differentiate into mature fates as a potential mechanism of WMS. Possessing a reliable and reproducible animal model of WMS may be significant in the study of OPC proliferation and differentiation, axonal remyelination, and neural repair post-stroke.

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Nov 17th, 12:30 PM Nov 17th, 2:30 PM

Time Course of Ischemia and Cell Death in a Mouse Model of White Matter Stroke

HARBESON 13

White matter stroke(WMS), constituting 15-25% of all stroke subtypes, is a progressive disease that often results in severe vascular disruption and cell death within infarct and peri-infarct regions. Although the impacts are devastating, the short and long-term pathological effects of ischemia in the white matter have not been fully explored yet due to the underdevelopment of animal models for research and treatments. Using an in vivo novel mouse model to induce subcortical WMS that similarly mimic the size and location of the disease in humans, we aim to assess the vasculature to determine endothelial fates and vascular repair at key time points, and characterize cellular apoptosis and recovery levels post-stroke. For this study, WMS is induced by stereotactically injecting a small molecule vasoconstrictor, N-iminoethyl-L-ornithine(L-NIO), along 3 sites of the corpus callosum to create a localized ischemia. After recovery, conjugated FITC-dextran is injected transcardially prior to sacrifice to label perfusing vessels and is co-stained with endothelial markers to determine vascular damage. Results from quantification of blood vessels show vascular impairments up to 15 days post-stroke, suggesting that the model is capable of creating not just transient ischemia but persistent vascular damages. Using combined methods terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) assay and immunohistochemistry, identified cell types experiencing apoptosis post-stroke primarily include oligodendrocytes, oligodendrocyte precursor cells(OPCs), and astrocytes. Preliminary cell quantification demonstrate correlation between cell death and recovery time points in astrocytes and oligodendrocytes; However, populations of OPCs continue to experience apoptotic death and proliferation in the same time period. Fate mapping OPCs using EdU assay further demonstrate their failure to differentiate into mature fates as a potential mechanism of WMS. Possessing a reliable and reproducible animal model of WMS may be significant in the study of OPC proliferation and differentiation, axonal remyelination, and neural repair post-stroke.