Hypertension-Induced Neurovascular and Cognitive Dysfunction at Single-Cell Resolution. Schaeffer and Pacholko et al.

These Imaris image files accompany the raw microscopy and Imaris image data in version 1, accessed at 10.17632/8jkmn4p2px.1. This data was uploaded separately due to file size limitations.

Hypertension is a leading cause of cognitive impairment, attributed to cerebrovascular insufficiency, blood-brain barrier disruption, and white matter damage. However, how hypertension affects brain cells remains unclear. Using scRNA-seq in a mouse model of hypertension induced by angiotensin II, a peptide involved in human hypertension, we mapped neocortical transcriptomic changes before (3 days) and after (42 days) onset of neurovascular and cognitive deficits. Surprisingly, endothelial transport disruption and senescence, stalled oligodendrocyte differentiation, and interneuronal hypofunction and network imbalance emerged after 3 days, attributable to angiotensin II signaling. By 42 days, when cognitive impairment becomes apparent, deficits in myelination and axonal conduction, as well as neuronal mitochondrial dysfunction, developed. These findings reveal a previously unrecognized early vulnerability of endothelial cells, interneurons, and oligodendrocytes, and provide the molecular bases for subsequent neurovascular dysfunction and cognitive impairment in hypertension. These data constitute a valuable resource for future mechanistic studies and therapeutic target validation.