Objective: Peri-infarct depolarizations (PIDs) are spontaneous waves that propagate slowly across the penumbra region following stroke, contributing to secondary infarct growth and negatively affecting stroke outcomes. KATP channels are generally spread in the brain. Under conditions of ischemia and/or hypoxia, KATP channels play a cytoprotective role in neurons. However, it is still unknown whether KATP channels are involved in the initiation and propagation of PIDs.
Methods: The Kir6.1 knockout (Kir6.1-/-) mice, Kir6.2 knockout (Kir6.2-/-) mice, and wild-type C57Bl6 mice (n = 8) were used. The middle cerebral artery occlusion (MCAO) stroke model was made and PIDs were detected by an optical intrinsic signal (OIS) imaging system.
Results: Much more PIDs appeared in Kir6.1-/-mice than that in Kir6.2-/- and WT mice in both the first hour and 4 hours following MCAO (3.9 ± 0.7 vs. 1.5 ± 0.3, p < 0,05; 3.9 ± 0.7 vs. 1.9 ± 0.3, p < 0.05; 20.0 ± 2.5 vs. 10.4 ± 2.4, p < 0.05; 20.0 ± 2.5 vs. 11.3 ± 1.4, p < 0.05). Furthermore, the first PID occurred much earlier in Kir6.1-/- mice than that in Kir6.2-/- mice and WT mice (21.3 ± 2.1 min vs. 34.1 ± 4.8 min, p < 0.05; 21.3 ± 2.1 min vs. 38.8 ± 3.4 min, p < 0.01). No significant differences in other characteristics of PIDs including originating sites, duration time, propagation patterns, and velocity were detected. Additionally, the migration of originating sites was observed.
Conclusion: This study shows that loss of Kir6.1, not Kir6.2 facilitates the induction of PIDs in focal cerebral ischemia, indicating that Kir6.1-forming channels in the brain may provide protection against PIDs.
Keywords: Focal cerebral ischemia; KATP channels; middle cerebral artery occlusion model; optical intrinsic signal imaging; peri-infarct depolarization.