HomeScience and ResearchScientific ResearchAre Scientists Finally Winning the War Against Strokes?

Are Scientists Finally Winning the War Against Strokes?

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Breakthrough in Stroke Treatment: Researchers Find Protein that Enhances Neural Growth and Motor Functions

Ischemic stroke, which is caused by a blockage of blood flow to the brain, is a leading cause of mortality and disability. Although the timely administration of a blood clot-dissolving drug is the current standard of care, there is an urgent need for improved treatments that can enhance patient outcomes. Reducing inflammation and rebuilding damaged neuronal connections are important therapeutic priorities, yet identifying a molecule that can achieve these effects has been challenging.

However, Osaka University researchers have identified two proteins, R-spondin 3 (RSPO3) and LGR4, that trigger a signaling pathway in cells to reduce inflammation in the ischemic brain and stimulate neurite outgrowth, a process that involves the growth of extensions from neurons.

This discovery, published today in the journal Stroke, provides new hope for stroke patients.

“Previous studies showed that RSPO3 was beneficial in lung injuries caused by inflammation. We also knew that RSPO3 stimulates a signaling pathway, named the ‘canonical Wnt pathway’, that promotes neurite outgrowth,” remarks lead author Munehisa Shimamura. “We wondered whether RSPO3 reduces inflammation and promotes neurite outgrowth after ischemic stroke.”

Earlier research studies have established the presence of RSPO3 and LGR4 in the same brain structures, and have demonstrated that RSPO3 activates LGR4 to activate the canonical Wnt pathway. In their study, the team from Osaka University identified RSPO3 in endothelial cells and LGR4 in microglia/macrophage cells and neurons present in the ischemic brain.

“Because of this close localization, RSPO3 could act on LGR4,” adds senior author Hironori Nakagami. “To test this hypothesis, we injected RSPO3 into the brains of mice 24 and 48 hours after ischemic stroke.”

Remarkably, mice that received injections of RSPO3 nine days after the stroke showed fewer sensory and motor deficits than those injected with a control protein. This was accompanied by a reduction in the expression of pro-inflammatory factors and an increase in neurite outgrowth. The researchers discovered that RSPO3/LGR4 reduced the expression of TLR4, a protein essential for inducing inflammation.

These findings are particularly noteworthy because the mice were treated with RSPO3 one day after the stroke, suggesting the possibility of its effectiveness in later stages of stroke. Therefore, targeting RSPO3/LGR4 signaling could offer a promising approach to developing new therapies for ischemic stroke and improving patient outcomes.

Source: 10.1161/STROKEAHA.122.041970

Image Credit: Getty

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