Background

An ischaemic stroke cuts off blood and oxygen to part of the brain, damaging brain cells and triggering swelling and inflammation. Among the first structures affected are the tiny blood vessels that make up the blood–brain barrier (BBB) — a tightly sealed layer of cells that normally shields the brain from harmful substances in the blood. When the BBB breaks down after a stroke, it worsens brain injury, so repairing it has become an important treatment goal, alongside protecting brain cells themselves.

Research

The team built a human blood–brain barrier model from stem cells and pericytes, then exposed it to a lack of oxygen and glucose followed by a recovery period, mimicking a stroke and its aftermath. They then tested SAHA (vorinostat), an already-approved cancer drug that alters how genes are switched on and off, applying it only after the simulated stroke — during the recovery phase, similar to how it would be used in a real patient. SAHA restored the barrier’s tightness, boosted levels of claudin-5 (a key protein that seals gaps between brain blood vessel cells), rebuilt a protective sugar coating on the cell surface (the glycocalyx), and shifted the cells’ energy production back toward a healthier, oxygen-based mode. The researchers also traced these effects to changes in gene activity, including a cell-signalling pathway (Wnt signalling) that favours barrier repair over uncontrolled cell growth.

Potential Impact

This is the first evidence that SAHA can directly protect and repair the blood–brain barrier itself, not just nerve cells, in a stroke model. Because SAHA is already an FDA-approved drug with a well-understood safety profile, it could potentially be repurposed as an add-on treatment for stroke, given during the recovery window to limit ongoing brain damage. As this is a lab-based cell model rather than an animal or human trial, further studies are needed before any clinical use.