Carbonic anhydrase inhibitors prevent presymptomatic capillary flow disturbances in a model of cerebral amyloidosis.

Introduction: Disturbances in microvascular flow dynamics are hypothesized to precede the symptomatic phase of Alzheimer's disease (AD). However, evidence in presymptomatic AD remains elusive, underscoring the need for therapies targeting these early vascular changes.

Methods: We employed a multimodal approach, combining in vivo optical imaging, molecular techniques, and ex vivo MRI, to investigate early capillary dysfunction in Tg-SwDI mice without memory impairment.

The effect of hypoxia on ZEB1 expression in a mimetic system of the blood-brain barrier.

The blood-brain barrier consists of a tightly sealed monolayer of endothelial cells being vital in maintaining a stable intracerebral microenvironment. The barrier is receptive to leakage upon exposure to environmental factors, like hypoxia, and its disruption has been suggested as a constituent in the pathophysiology of both neurological and psychiatric disorders. The schizophrenia associated ZEB1 gene encodes a transcription factor susceptible to transcriptional control by a hypoxia induced factor, HIF1A, known to be implicated in blood-brain barrier dysfunction.