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Author Notes:

Srikant Rangaraju: srikant.rangaraju@emory.edu

SRan, SAR, TG, SRam, and MY are responsible for the conceptualization; SRan, SAR, TG, AT, SRam, HX, NN, LC, and MY are responsible for the methodology; SRan, SAR, TG, SRam, AT, and MY are responsible for the investigation; SRan, SAR, and TG are responsible for the methodology writing and original draft; SRan and MY are responsible for the writing the review and editing, funding acquisition, resources, and supervision.

All authors read and approved the final manuscript.

We thank Dr. Allan I. Levey for critically reading this manuscript.

The authors declare that they have no competing interests.


Research Funding:

This study was supported by Alzheimer’s Association AARG 37102 (S.R.); NIH K08-NS099474-1 (S.R.); NS-091201 (M.Y); NS-079331 (M.Y.); and VA MERIT Award IO1BX003441 (M.Y).

This study was supported in part by the Emory Flow Cytometry Core (EFCC), one of the Emory Integrated Core Facilities (EICF) and is subsidized by the Emory University School of Medicine.

Additional support was provided by the Georgia Clinical & Translational Science Alliance of the NIH under Award Number UL1TR002378.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Neurosciences
  • Neurosciences & Neurology
  • Ischemic stroke
  • Kv1
  • 3
  • Macrophage
  • Microglia
  • Middle cerebral artery occlusion
  • Neuroinflammation

Temporal profiling of Kv1.3 channel expression in brain mononuclear phagocytes following ischemic stroke

Journal Title:

Journal of Neuroinflammation


Volume 16, Number 1


, Pages 116-116

Type of Work:

Article | Final Publisher PDF


Background: Microglia and CNS-infiltrating monocytes/macrophages (CNS-MPs) perform pro-inflammatory and protective anti-inflammatory functions following ischemic stroke. Selective inhibition of pro-inflammatory responses can be achieved by Kv1.3 channel blockade, resulting in a lower infarct size in the transient middle cerebral artery occlusion (tMCAO) model. Whether beneficial effects of Kv1.3 blockers are mediated by targeting microglia or CNS-infiltrating monocytes/macrophages remains unclear. Methods: In the 30-min tMCAO mouse model, we profiled functional cell-surface Kv1.3 channels and phagocytic properties of acutely isolated CNS-MPs at various timepoints post-reperfusion. Kv1.3 channels were flow cytometrically detected using fluorescein-conjugated Kv1.3-binding peptide ShK-F6CA as well as by immunohistochemistry. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was performed to measure Kv1.3 (Kcna3) and Kir2.1 (Kcnj2) gene expression. Phagocytosis of 1-μm microspheres by acutely isolated CNS-MPs was measured by flow cytometry. Results: In flow cytometric assays, Kv1.3 channel expression by CD11b+ CNS-MPs was increased between 24 and 72 h post-tMCAO and decreased by 7 days post-tMCAO. Increased Kv1.3 expression was restricted to CD11b+CD45lowLy6clow (microglia) and CD11b+CD45highLy6Clow CNS-MPs but not CD11b+CD45highLy6chigh inflammatory monocytes/macrophages. In immunohistochemical studies, Kv1.3 protein expression was increased in Iba1+ microglia at 24-48 h post-tMCAO. No change in Kv1.3 mRNA in CNS-MPs was observed following tMCAO. Conclusions: We conclude that resident microglia and a subset of CD45highLy6clow CNS-MPs are the likely cellular targets of Kv1.3 blockers and the delayed phase of neuroinflammation is the optimal therapeutic window for Kv1.3 blockade in ischemic stroke.

Copyright information:

© 2019 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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