Abstract 496: Genetic Neutrophil Deficiency Ameliorates Cerebral Ischemia-Reperfusion Injury
0301 basic medicine
03 medical and health sciences
0302 clinical medicine
3. Good health
DOI:
10.1161/atvb.37.suppl_1.496
Publication Date:
2021-07-02T23:44:11Z
AUTHORS (5)
ABSTRACT
Background:
Neutrophils respond rapidly to cerebral ischemia and are thought to contribute to inflammation-mediated injury during stroke. Neutralizing antibodies and inhibition of neutrophil chemotactic molecules can be protective during models of stroke, but many of these techniques have the potential to result in cross-reactivity and non-specificity with other immune cell types. Using myeloid Mcl1 knockout mice as a model of genetic neutrophil deficiency, we investigated the contribution of neutrophils to stroke pathophysiology.
Methods:
Myeloid Mcl1 knockout mice were subjected to transient 90-min middle cerebral artery occlusion and infarct size was assessed by MRI after 24 hours reperfusion. Immune cell mobilization and infiltration was assessed by flow cytometry after 24 hours reperfusion.
Results:
We found that myeloid Mcl1 knockout mice had significantly reduced infarct size when compared to heterozygous and wild type control mice (MyMcl1
+/+
: 78.0 mm
3
; MyMcl1
+/-
: 83.4 mm
3
; MyMcl1
-/-
: 55.1 mm
3
). This was accompanied by a nearly complete absence of neutrophils in the ischemic hemisphere of myeloid Mcl1 knockout mice. Although myeloid Mcl1 knockout mice were protected from cerebral infarction, no significant differences in the expression of inflammatory genes were detected. Inhibition of neutrophil chemotaxis using CXCR2 pepducin treatment partially reduced neutrophil mobilization and recruitment to the brain after stroke, but did not reduce infarct size 24 hours after transient MCA occlusion.
Conclusions:
These data confirm that neutrophils have an important role in infarct development during stroke pathophysiology and suggest that complete deficiency, but not partial inhibition, is necessary to prevent neutrophil-mediated injury during stroke.
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