Potassium channelopathy-like defect underlies early-stage cerebrovascular dysfunction in a genetic model of small vessel disease
Abstract
Small vessel disease (SVD) of the brain refers to a group of pathological processes leading to cerebral lesions, cognitive decline, and stroke. Despite the importance of SVD, there is no specific treatment, mainly due to a limited understanding of the disease pathogenesis. Using a recently developed mouse model of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a hereditary form of SVD, we determined the basis of altered brain artery function at an early stage of disease progression. We found that cerebrospecific up-regulation of the voltage-gated potassium channel, KV1, prevents intracerebral arterioles from constricting in response to physiological levels of intraluminal pressure. This impairment of a fundamental vascular function is expected to impact cerebral blood flow autoregulation and local dilation in response to neuronal activity (functional hyperemia).
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- February 2015
- DOI:
- 10.1073/pnas.1420765112
- Bibcode:
- 2015PNAS..112E.796D