The potassium channel Kv1.3 as a therapeutic target for immunocytoprotection after reperfusion

Figures

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  Figure 1. Comparison of stroke severity in young and old female versus male mice. Percent of infarcted hemisphere area was determined by T2‐weighted MRI on day 8 after daily neurological deficit scoring. (A) Infarct area and deficit score in 16‐week‐old female (n = 11) were compared to male (n = 10) mice (p < 0.001 for infarct, p = 0.029 for NES). (B) Infarct area and deficit score in 80‐week‐old female (n = 9) were compared to male (n = 9) mice (p = 0.623 for infarct, p = 0.446 for NES). Data are shown as whisker plots with data overlay. The boxes show mean ± SEM and the whiskers show confidence intervals.

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  Figure 2. Kv1.3 is expressed on microglia/macrophages and T cells in the infarct of an 80‐week‐old female mouse. (A) Sample immunofluorescence staining of 5‐µm thick paraffin sections from the 6‐mm slice of an 80‐week‐old female mouse on day 8 after tMCAO. (A) Kv1.3 staining colocalizes to Iba‐1+ cells. (B) Kv1.3 staining on smaller, CD3+ T cells (white arrowheads).

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  Figure 3. Comparison of stroke severity in WT versus Kv1.3−/− mice. (A) Infarct area and deficit score in 16‐week‐old WT (n = 10) were compared to Kv1.3−/− (n = 14) male mice (p < 0.001 for infarct, p = 0.033 for NES). (B) Infarct area and deficit score in 16‐week‐old WT (n = 11) were compared to Kv1.3−/− (n = 14) female mice (p = 0.058 for infarct, p = 0.551 for NES). (C) Infarct area and deficit score in 80‐week‐old WT (n = 9) were compared to Kv1.3−/− (n = 12) male mice (p = 0.056 for infarct, p < 0.001 for NES). (D) Infarct area and deficit score in 80‐week‐old WT (n = 9) were compared to Kv1.3−/− (n = 18) female mice (p = 0.001 for infarct, p < 0.001 for NES). Data are shown as whisker plots with data overlay. The boxes show mean ± SEM and the whiskers show confidence intervals.

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  Figure 4. The Kv1.3 blocker PAP‐1 reduces infarction and improves neurological deficit in young and old WT female mice. (A) Infarct area and deficit score in vehicle (n = 11) were compared to PAP‐1 (40 mg/kg; n = 15) treated 16‐week‐old female mice (p = 0.007 for infarct, p = 0.016 for NES). (B) Infarct area and deficit score in vehicle (n = 9) were compared to PAP‐1 (40 mg/kg; n = 9) treated 80‐week‐old female mice (p = 0.032 for infarct, p = 0.003 for NES). Data are shown as whisker plots with data overlay. The boxes show mean ± SEM and the whiskers show confidence intervals.

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  Figure 5. PAP‐1 treatment and Kv1.3 deletion reduce Iba‐1 and CD3 staining in 80‐week‐old female mice. Serial paraffin sections (5 µm thick) cut at 4 mm and the 6 mm from 80‐week‐old female mice were stained for Iba‐1 and CD3. (A) Percentage of Iba‐1‐positive pixels in the infarcted hemisphere. Vehicle‐treated WT (n = 9), PAP‐1‐treated WT (n = 9, p = 0.120 for 4‐mm section; p = 0.014 for 6‐mm section), and Kv1.3−/− (n = 18, p = 0.011 for 4‐mm section; p = 0.007 for 6‐mm section). (B) Percentage of CD3‐positive pixels in the infarcted hemisphere. Vehicle‐treated WT (n = 9), PAP‐1‐treated WT (n = 9, p = 0.049 for 4‐mm section; p = 0.027 for 6‐mm section), and Kv1.3−/− (n = 18, p < 0.001 for 4‐mm section; p = 0.002 for 6‐mm section). Data are shown as whisker plots with individual data overlay. The boxes show mean ± SEM and the whiskers show confidence intervals.