In conclusion, this study, through transcriptomic and bioinformatics analysis, unveils the molecular mechanisms underlying early stent implantation in improving neurovascular unit damage and CMD in severe ICAS, particularly highlighting the significant changes in ICAM1 expression and its role in the NF‐κB pathway as critical factors in reducing the risk of watershed infarcts. This evidence concerns the gene ICAM1 and familial isolated congenital asplenia.