Effect of Kv Channel Blockers on Infarct Size and Neurological Severity Score in Rodent Models of Brain Ischemia: A Systematic Review and Meta-analysis

Abstract

Background: Ischemic stroke is a leading cause of disability with limited approved treatment. Recently, Kv channel blockers have gained attention for their neuroprotective properties. This systematic review evaluates the effects of Kv channel blockers on infarct size and neurological severity score (NSS) in rodent models of ischemic stroke. Materials and methods: This study adhered to the PRISMA guidelines. In April 2024, a systematic search was carried out across several databases, such as Medline, Embase, PubMed, CINAHL, Cochrane Library, Web of Science, and Scopus. Additionally, Google Scholar was explored to identify further relevant articles. We included all experimental studies that reported the effects of Kv channel blockers on rodent models of stroke. The quality of the included studies was assessed using the CAMARADES critical appraisal tool, and a quantitative synthesis was performed using CMA v.3 software. Results: Out of 1,211 studies screened, 8 were included in the analysis. Eight of these studies looked at infarct size using histology, magnetic resonance imaging (MRI), and triphenyl tetrazolium chloride (TTC) staining. Six of them looked at NSS on days 4, 7, and 8 after the stroke. The quantitative synthesis indicated substantial disparities between the treatment and vehicle groups in both infarct size (standardized mean difference [SMD]: 1.67; 95% CI: 0.90–2.45; p < 0.001) and NSS (SMD: 1.65; 95% CI: 1.25–2.04; p < 0.001). Conclusion: This meta-analysis demonstrated that Kv channel blockers effectively reduce infarct size and improve NSS in preclinical models of ischemic stroke. Findings suggest the Kv channel blockers as potential therapeutic agents and warrant further investigation in clinical studies.

Keywords: Voltage gated potassium channels, Ischemic stroke, Infarct size, Neurological severity score, Rodent