Lower cerebral blood flow but not cerebrovascular response in elastin haploinsufficient mice

Elastin insufficiency is associated with structural differences in the large elastic arteries and cerebral artery dysfunction. However, previous studies have not assessed potential sex differences in cerebrovascular function. We measured cerebral blood flow (CBF) using arterial spin labeling MRI at rest and in response to hypercapnia challenge (cerebrovascular responsiveness, CR) in middle-aged and old elastin haploinsufficient (Eln^+/-) and wild-type (Eln^+/+) mice. We also assessed neuroinflammation by microglia and astrocyte cell counts. We found that Eln^+/- mice had a significantly lower resting CBF in the cerebral cortex compared with Eln^+/+ mice, with similar non-significant trends in the hippocampus and thalamus. In contrast, the Eln^+/- mice had an intact hypercapnic response, resulting in better CR compared with Eln^+/+ in hippocampus, with a similar trend in the cerebral cortex. Sex did not impact CBF or CR. We found that Eln^+/- mice had lower hippocampal volume compared with Eln^+/+ mice. Glia cell counts were highly dependent on brain region, with Eln^+/- mice having more microglia in the cerebral cortex, but fewer astrocytes in the hippocampus compared with Eln^+/+ mice. While sex also impacted glial cell counts, we found no interactions between sex and Eln genotype. Our results demonstrate that elastin haploinsufficiency results in lower resting CBF, but greater CR.