Northwestern University researchers have developed an injectable nanomaterial that may help reduce secondary brain injury following ischemic stroke. The new therapy, tested in mice, is designed to protect the brain during the period after blood flow is restored—a time when additional damage can occur due to inflammation and cell death.
The study, published January 7 in Neurotherapeutics, involved delivering a single intravenous dose of the material immediately after restoring blood flow in a mouse model of ischemic stroke. The nanomaterial was able to cross the blood-brain barrier and reach the damaged tissue. Mice treated with the therapy experienced less brain damage compared to untreated mice, and no significant side effects or organ toxicity were observed during seven days of monitoring.
"Current clinical approaches are entirely focused on blood flow restoration," said Dr. Ayush Batra, co-corresponding author and associate professor at Northwestern University Feinberg School of Medicine. "Any treatment that facilitates neuronal recovery and minimizes injury would be very powerful, but that holy grail doesn't yet exist. This study is promising because it's leading us down a pathway to develop these technologies and therapeutics for this unmet need."
The injectable treatment uses supramolecular therapeutic peptides (STPs), building on earlier work by Northwestern's Samuel I. Stupp. In previous research, similar technology—sometimes referred to as "dancing molecules" due to their dynamic properties—was shown to reverse paralysis in mice with spinal cord injuries after a single injection at the injury site.
"One of the most promising aspects of this study is that we were able to show this therapeutic technology, which has shown incredible promise in spinal cord injury, can now begin to be applied in a stroke model and that it can be delivered systemically," said Stupp, co-corresponding author and Board of Trustees Professor at Northwestern. "This systemic delivery mechanism and the ability to cross the blood-brain barrier is a significant advance that could also be useful in treating traumatic brain injuries and neurodegenerative diseases such as ALS."
Ischemic strokes make up about 80% of all strokes in the United States. They occur when a clot blocks blood flow to part of the brain; restoring circulation quickly is critical but can also trigger additional injury known as reperfusion damage.
"It has not only a significant personal and emotional burden on patients, but also a financial burden on families and communities," Batra said. "Reducing this level of disability with a therapy that could potentially help in restoring function and minimizing injury would really have a powerful long-term impact."
Researchers say their mouse model closely mimics real-world clinical scenarios for ischemic stroke treatment by blocking then restoring blood flow—a process called reperfusion—similar to what patients experience during emergency care.
Stupp explained that both pro-regenerative and anti-inflammatory effects contributed to positive outcomes: "You get an accumulation of harmful molecules once the blockage occurs and then suddenly you remove the clot and all those 'bad actors' get released into the bloodstream, where they cause additional damage," he said. "But the dancing molecules carry with them some anti-inflammatory activity to counteract these effects and at the same time help repair neural networks."
The team adjusted peptide concentrations so that smaller aggregates could cross into brain tissue more easily before forming larger assemblies there for greater therapeutic effect.
"We chose for this stroke study one of the most dynamic therapies we had in terms of its molecular structure so that supramolecular assemblies would have a better probability of crossing the blood-brain barrier," Stupp said.
Batra noted that increased permeability at sites where blood flow has just been restored creates an opportunity for targeted drug delivery: "Add to that a dynamic peptide that is able to cross more readily, and you're really optimizing the chances that your therapy is going where you want it to go," he said.
Further research will explore whether this approach supports longer-term recovery or improves cognitive outcomes after stroke. The team also plans to investigate whether adding other regenerative signals could enhance results.
The paper’s first authors are graduate student Zijun Gao and postdoctoral researcher Luisa Andrade da Silva. Funding came primarily from Northwestern’s Center for Regenerative Nanomedicine through its SQI Synthesizer Grant Program.
