Controlled “oxidative spark”: a surprising ally in brain repair

(Press-News.org) Oxidative stress is a direct consequence of an excess in the body of so-called “free radicals” – reactive, unstable molecules that contain oxygen. Free radicals are normal metabolic by-products and also help to relay signals in the body. In turn, oxidative stress (an overload of these molecules) can be caused by lifestyle, environmental and biological factors such as smoking, high alcohol consumption, poor diet, stress, pollution, radiation, industrial chemicals, and chronic inflammation. When this occurs, it creates an imbalance between the production of free radicals and the body's antioxidant defenses, which are responsible for neutralizing them.

When we hear about “oxidative stress” in the brain, it is almost always bad news, linked to ageing, Alzheimer’s and other neurodegenerative diseases. But new research in fruit flies, published today (10/02/2026) in the journal EMBO Reports by a team from the Champalimaud Foundation (CF), in Lisbon, shows that a brief, well‑controlled burst of oxidative stress right after an injury can actually help the brain repair itself. 

In the new study, Christa Rhiner – principal investigator of the Stem Cells and Regeneration Lab at the CF – and her team show that, after a small injury in the adult fly brain, a specific group of support cells, known as glia, rapidly release a pulse of chemically reactive forms of oxygen that include hydrogen peroxide. This controlled “oxidative spark” does two things at once: it switches on protective antioxidant processes in glia and, crucially, acts as a signal that wakes up normally quiet cells and drives them to divide and replace lost tissue.

The team traced this burst of free radicals to an enzyme called Duox, which sits in glial cell membranes and produces hydrogen peroxide outside the cell. “ This was surprising, as we initially thought that mitochondria – the tiny power plants within cells -- would be the main generators of oxidative stress in the injured brain”, explains first co-author Carolina Alves.

When she reduced Duox activity genetically, or decreased the amount of reactive oxygen with antioxidant treatments, the injured brains produced fewer new cells and the regenerative response was markedly blunted. In contrast, nudging glia to increase Duox activity was enough to trigger extra cell divisions even without an injury. This means, in particular, that glia-derived hydrogen peroxide is a powerful driver of brain plasticity.

Further experiments revealed how this response is wired. Injury first boosts calcium levels inside glia, which in turn activates Duox. The hydrogen peroxide then spreads locally through the tissue and helps keep a pro-regenerative (repair) pathway active for days after the initial injury – long enough to support sustained cell division and repair. And while the injured brain tissue does show some oxidative damage to lipids, the ramping up antioxidant defences by glial cells appears to limit harm from the transitory oxidative burst.

These findings challenge the simplistic idea that all oxidative stress is detrimental in the brain, and may help explain why broad antioxidant therapies have largely failed to improve recovery after brain injury in patients. 

Long-lasting oxidative stress and particularly reactive oxygen species that immediately attack cellular components are highly damaging for the brain. “However our work suggests that certain, precisely timed reactive oxygen signals are an integral part of the brain’s own repair toolkit”, stresses Rhiner.

In the future, more targeted strategies that dampen damaging, chronic oxidative stress while preserving – or even harnessing – these short-lived pro-healing signals could open new avenues to promote brain repair.

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