Interferon-γ drives macrophage reprogramming, cerebrovascular remodeling, and cognitive dysfunction in a zebrafish and a mouse model of ion imbalance and pressure overload.

Hypertension is a major risk factor for damages of the vasculature, heart, and brain, and thereby a major healthcare burden. Inadequate cerebral blood supply due to altered cerebrovascular structure and vasoregulatory disruption upon hypertension render the brain highly susceptible to stroke and cognitive decline. We envision that the cellular and molecular mechanisms uncovered here linking immune dysregulation to cerebrovascular remodeling and functional impairment of the brain will inform future development of immunomodulatory therapeutic strategies for counteracting derangement of macrophage/microglia activation and their vasculo/neuroprotective function in response to systemic inflammation in hypertension.