# Inhibition of leukocyte migration after ischemic stroke by VE‐cadherin mutation in a mouse model leads to reduced infarct volumes and improved motor skills

## TL;DR

Blocking white blood cell movement in mice after stroke reduces brain damage and improves motor function, but only when a specific protein mutation is present.

## Contribution

The study demonstrates that selective inhibition of leukocyte migration via a specific VE-cadherin mutation reduces infarct size and improves motor skills in a mouse stroke model.

## Key findings

- Y731F mutation in VE-cadherin reduces infarct volume and improves motor skills in stroke mice.
- Y685F mutation does not affect structural or functional outcomes in stroke mice.
- VE-cadherin mutations do not alter immune cell count or distribution in ischemic brain tissue.

## Abstract

To distinguish between the genuine cellular impact of the ischemic cascade by leukocytes and unspecific effects of edema and humoral components, two knock‐in mouse lines were utilized. Mouse lines Y731F and Y685F possess point mutations in VE‐cadherin, which lead to a selective inhibition of transendothelial leukocyte migration or impaired vascular permeability.

Ischemic stroke was induced by a model of middle cerebral artery occlusion. Analysis contained structural outcomes (infarct volume and extent of brain edema), functional outcomes (survival analysis, rotarod test, and neuroscore), and the extent and spatial distribution of leukocyte migration (heatmaps and fluorescence‐activated cell sorting (FACS) analysis).

Inhibition of transendothelial leukocyte migration as in Y731F mice leads to smaller infarct volumes (52.33 ± 4719 vs. 70.43 ± 6483 mm3, p = .0252) and improved motor skills (rotarod test: 85.52 ± 13.24 s vs. 43.06 ± 15.32 s, p = .0285). An impaired vascular permeability as in Y685F mice showed no effect on structural or functional outcomes. Both VE‐cadherin mutations did not influence the total immune cell count or spatial distribution in ischemic brain parenchyma.

Selective inhibition of transendothelial leukocyte migration by VE‐cadherin mutation after ischemic stroke in a mouse model leads to smaller infarct volumes and improved motor skills.

Inhibition of leukocyte migration after ischemic stroke by VE‐cadherin mutation in a mouse model leads to reduced infarct volumes and improved motor skills. VE‐cadherin mutation Y731F is associated with a selective inhibition of transendothelial leukocyte migration. In a mouse model of ischemic stroke, it led to smaller infarct volumes and improved motor skills. VE‐cadherin mutation Y685F had no effect on structural or functional outcomes on the same mouse model of ischemic stroke.