Canonical Transient Receptor Potential Channel 3 Contributes to Cerebral Blood Flow Changes Associated with Cortical Spreading Depression in Mice

Figures

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  Figure 1. Representative CBF responses in a littermate control mouse to different concentrations of K+ applied to a cranial window. An LSI image was collected every 4 s and the flux (CBF measured using LSI) of the region of interest (indicated with the red oval was plotted in the lower panel. The timing of drug applications and washout was indicated with artifacts in the LSI imaging. Images at the top were taken at indicated time points (a–i) in the bottom panel. Note that lower concentrations of K+ results in an increase in CBF whereas high K+ results in a transient decrease (I) in CBF followed by a transient increase (II).

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  Figure 2. Quantitative comparisons of CBF changes elicited by (a) 2 mM KCl; (b) 6 mM KCl; and (c) 50 mM KCl. There is no statistically significant difference between control mice (n = 7) and TRPC3KO mice (n = 7).

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  Figure 3. Comparison of CBF changes associated with high K+-induced spreading depression in TRPC3KO (n = 6) and control mice (n = 7). Note that there is a highly significant genotype effect (p < 0.001, Two-way ANOVA; *: p < 0.05, **: p < 0.01, Bonferroni posttests).

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  Figure 4. Quantitative comparison of 3 major phases of hemodynamic responses associated with high K+-induced cortical depression between TRPC3KO mice (n = 6) and controls (n = 7). The first (I) and second (II) changes in CBF were quantified (a,b) and the late CBF changes (4 min after high K+ bolus) were also measured (c). *: p < 0.05, unpaired t-test.

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  Figure 5. Hemodynamic responses associated with high NMDA-induced cortical depression. (a) Representative CBF changes after bolus application of NMDA in TRPC3KO mice and controls. Note that a sustained increase in CBF was observed in TRPC3KO mice, whereas a transient increase in CBF was typical in control mice. (b) Comparison of the peak CBF increase in TRPC3KO mice (n = 4) and controls (n = 7). **: p < 0.01, unpaired t-test. (c) Comparison of the late CBF changes (approximately 4 min after NMDA application) in TRPC3KO mice (n = 4) and controls (n = 7). *: p < 0.05, un-paired t-test.

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  Figure 6. Hemodynamic responses associated with needle-prick-induced cortical depression. (a) Representative CBF changes after a needle prick in TRPC3KO mice and controls. (b) Comparison of the CBF changes 2–3 min after needle prick in TRPC3KO mice (n = 6) and controls (n = 7). ***: p < 0.001, unpaired t-test.