Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes.

Autor: Saxena S; Department of Anesthesia and Critical Care, AZ Sint-Jan Brugge Oostende AV, Bruges, Belgium. sarah.saxena@ulb.be., Nuyens V; Experimental Medicine Laboratory, ULB 222 Unit, CHU-Charleroi, Université Libre de Bruxelles, Montigny-Le-Tilleul, Belgium., Rodts C; Department of Anesthesiology, CHU-Charleroi, Université Libre de Bruxelles, Charleroi, Belgium., Jamar K; Department of Anesthesiology, CHU-Charleroi, Université Libre de Bruxelles, Charleroi, Belgium., Albert A; Department of Biostatistics (B-STAT), University Hospital of Liège, Liège, Belgium., Seidel L; Department of Biostatistics (B-STAT), University Hospital of Liège, Liège, Belgium., Cherkaoui-Malki M; Laboratoire Bio-PeroxIL EA7270, Univ. Bourgogne Franche-Comté, 6 Bd Gabriel, 21000, Dijon, France., Boogaerts JG; Department of Anesthesiology, CHU-Charleroi, Université Libre de Bruxelles, Charleroi, Belgium., Wulff H; Department of Pharmacology, University of California Davis, Davis, CA, USA., Maze M; Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, UCSF, San Francisco, CA, USA., Kruys V; Laboratory of Molecular Biology of the Gene, Department of Molecular Biology, Université Libre de Bruxelles (ULB), Gosselies, Belgium., Vamecq J; Inserm, Biochemistry and Molecular Biology Laboratory, HMNO, CBP, CHU Lille & EA 7364 - RADEME, North France University Lille, Lille, France.
Jazyk: angličtina
Zdroj: BMC anesthesiology [BMC Anesthesiol] 2023 Mar 16; Vol. 23 (1), pp. 80. Date of Electronic Publication: 2023 Mar 16.
DOI: 10.1186/s12871-023-02030-2
Abstrakt: Background: Potassium channels (KCa3.1; Kv1.3; Kir2.1) are necessary for microglial activation, a pivotal requirement for the development of Perioperative Neurocognitive Disorders (PNDs). We previously reported on the role of microglial Kv1.3 for PNDs; the present study sought to determine whether inhibiting KCa3.1 channel activity affects neuroinflammation and prevents development of PND.
Methods: Mice (wild-type [WT] and KCa3.1 -/- ) underwent aseptic tibial fracture trauma under isoflurane anesthesia or received anesthesia alone. WT mice received either TRAM34 (a specific KCa3.1 channel inhibitor) dissolved in its vehicle (miglyol) or miglyol alone. Spatial memory was assessed in the Y-maze paradigm 6 h post-surgery/anesthesia. Circulating interleukin-6 (IL-6) and high mobility group box-1 protein (HMGB1) were assessed by ELISA, and microglial activitation Iba-1 staining.
Results: In WT mice surgery induced significant cognitive decline in the Y-maze test, p = 0.019), microgliosis (p = 0.001), and increases in plasma IL-6 (p = 0.002) and HMGB1 (p = 0.001) when compared to anesthesia alone. TRAM34 administration attenuated the surgery-induced changes in cognition, microglial activation, and HMGB1 but not circulating IL-6 levels. In KCa3.1 -/- mice surgery neither affected cognition nor microgliosis, although circulating IL-6 levels did increase (p < 0.001).
Conclusion: Similar to our earlier report with Kv1.3, perioperative microglial KCa3.1 blockade decreases immediate perioperative cognitive changes, microgliosis as well as the peripheral trauma marker HMGB1 although surgery-induced IL-6 elevation was unchanged. Future research should address whether a synergistic interaction exists between blockade of Kv1.3 and KCa3.1 for preventing PNDs.
(© 2023. The Author(s).)
Databáze: MEDLINE
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