Multiple lifestyle-related risk factors, including smoking and diabetes mellitus, have been definitively associated with an increased incidence of ischemic stroke.1,2 Previous studies have analyzed genetic factors such as lipid metabolism that would alter stroke risk but not the traits that would affect pial collateral vessel anatomy or infarct size. The variability of vessel anatomy and time of symptom onset and the heterogeneity of treatment course have made it difficult to accurately pinpoint molecular targets responsible for postischemic injury. In the present study, Lee et al3 applied a forward genetic (phenotype-driven) strategy by mapping the natural allelic variation in inbred mouse strains to determine the genes involved in determining both infarct size and extent of pial collateralization. Through this approach, 12 genes that influence the extent of pial collaterals and infarct size were identified within the chromosome 7 loci, Civq1 and Canq1. Of these 12 genes, the authors determined that the IL-21 receptor (Il21r), found on immune cells and neurons, plays a major role in modulating infarct volume in vivo.
To examine differences in the pial collateral vessel anatomy between the Il21r−/−(KO) and Il21r+/+(WT) mouse strains, the authors measured the number of connections between the anterior cerebral artery, middle cerebral artery (MCA), and posterior cerebral artery in P21 mice. To accomplish this, the skull and dura were removed, and the pial circulation was observed under a stereomicroscope. The numbers of pial collaterals between the KO and WT group were 16.2 and 20.7 between the anterior cerebral artery and MCA territories and 16.6 and 20.1 between the MCA and posterior cerebral artery, respectively, a difference that was not significant (Figure). The authors concluded that IL21r is not the major gene encoding pial vessel anatomy under the chromosome 7 Canq1 locus.
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