ISC 2024 | Border associated macrophages in neurovascular and cognitive dysfunction

Costantino Iadecola, MD, Weill Cornell Medical College, Cornell University, New York, NY, shares insights from his recent research projects, shedding light on the immune compartments at the brain’s borders and their role in neurovascular disease. In a recent study using a mouse model of hypertension, neurovascular and cognitive dysfunction were shown to depend on interleukin (IL)-17. As well as increasing the level of circulating IL-17, IL-17-producing cells were shown to migrate from the gut to the meninges, releasing IL-17 in the cerebrospinal fluid and activating border-associated macrophages (BAMs). This led to increased superoxide production in BAMs, decreasing nitric oxide bioavailability and consequently, impairing vasodilation and neurovascular coupling. Prof. Iadecola explains the relevance of these BAMs in amyloid-beta immunotherapy, where the occurrence of amyloid related imaging abnormalities (ARIA) remains a substantial issue. Activation of perivascular macrophages by amyloid immunocomplexes has been demonstrated in mouse models, causing vascular oxidative stress and dysfunction. These studies pave the way for the development of innovative therapeutic approaches targeting BAMs. This interview took place during the International Stroke Conference 2024 in Phoenix, AZ.

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