It’s been more than three decades, but still there are only two treatments for a stroke: either rapid use of a clot-busting medication called tPA or surgical removal of a clot from the brain with mechanical thrombectomy. However, only 5% to 13% percent of stroke cases are actually eligible for these interventions.
“We need to be persistent with our research to find a new therapy for stroke,” says Rajkumar Verma, M.Pharm., Ph.D., assistant professor, Department of Neuroscience at UConn School of Medicine working in cross-campus collaboration with Professor Raman Bahal Ph.D. of the Department of Pharmaceutical Sciences in the UConn School of Pharmacy. “Stroke research is hard and challenging to do. But without trying we won’t make progress. We need to keep trying. UConn is determined to keep trying.”
In addition to being life-threatening, stroke is the major cause of long-term disability worldwide.
“When a stroke strikes a patient, we don’t have any treatment to offer to effectively repair the brain’s damage. Once brain cells and tissue are damaged by a stroke, nothing can help restore the damage. In essence, the cascading inflammation caused by a stroke in the brain is like a fire in a house. We need to find a way to stop stroke’s fire,” says Verma.
Verma and his multidisciplinary research team believe they have found a new innovative therapy to try to stop a stroke’s “fire” or inflammation. They have reported their new findings in the journal Molecular Therapy—Nucleic Acids.
To try to more effectively control a stroke’s damage and turn back time, UConn researchers are leveraging the power of micro-RNA (miRNA), small molecules that regulate protein expression inside cells as they are able to control multiple proteins at a time.
“MiRNAs are small RNA molecules that help cells to regulate multiple gene and protein expression,” says Verma. “UConn researchers discovered that during a stroke these miRNA get dysregulated, thus leading to brain damage by multiple unchecked proteins. Also, our laboratory research has confirmed the presence of increased levels of one such miRNA, known as miRNA-141-3p, in blood samples of stroke patients.”
Verma adds, “We are thrilled to report that we have successfully tested a novel miRNA-141-3p inhibitor synthesized in our collaborator Dr. Bahal’s lab with the ability to reduce stroke damage and extinguish spreading inflammatory fire in the brain. In mouse models, we have seen swift restoration of once-lost motor function and memory. Also, we see a decrease in brain injury and enhanced expression of neuroprotective genes and growth factors fueling the brain’s recovery from stroke.”
The new promising therapeutic modality developed to inhibit stroke is called anti-miR-141-3p. UConn’s medical school is currently working to commercialize the discovery and take it toward clinical trial testing as a future treatment option for stroke.
Verma says UConn’s research findings once again showcase the powerful tool of miRNA and the promise of their newly developed miRNA inhibitor’s ability to stop the overexpression of dangerous, dysregulated bad proteins causing inflammation in the brain post-stroke.
Verma came to the U.S. over a decade ago from India and continued his stroke research journey at UConn School of Medicine studying stroke.
“I saw the big therapeutic gap in a new drug treatment for stroke to mitigate its brain damage and help with post-stroke recovery, and was motivated to try to fill this gap by learning more about stroke and by performing more translational research. I have chosen to stay at UConn for my stroke research, as UConn excels at this.”
But Verma is also driven to fight stroke personally.
“So many people have a personal story or family member who has been personally impacted about stroke—including me,” Verma shares. “My father died from a cardiovascular incident. We are not sure if it was in the brain or the heart. But this experience has led to my motivation for pursuing more stroke research.” Seeing a Black Hole’s Jet in a New Light
Research led by the University of Michigan has pored over more than two decades’ worth of data from NASA’s Chandra X-Ray Observatory to show there’s new knotty science to discover around black holes.
In particular, the study looks at the high-energy jet of particles being blasted across space by the supermassive black hole at the center of the galaxy Centaurus A.
Jets are visible to different types of telescopes, including those that detect radio waves and others that collect X-rays. Since Chandra’s 1999 launch, many astronomers have been particularly interested in the unexpectedly bright X-ray signals from jets.
Still, it appeared that X-ray observations were essentially capturing the same features as their more established radio counterparts, which isn’t the most exciting outcome.
Jets are massive cosmic structures – some are larger than their host galaxies – that still harbor many mysteries. If a jet looks the same to different instruments, that doesn’t do any favors for the folks working to unravel these astrophysical puzzles.
“A key to understanding what’s going on in the jet could be understanding how different wavelength bands trace different parts of the environment,” said lead author David Bogensberger, a postdoctoral fellow at U-M. “Now we have that possibility.”
The new study is the latest entry in a small but growing body of research that’s digging deeper into data to spot subtle, meaningful differences between radio and X-ray observations.
“The jet in X-rays is different from the jet in radio waves,” Bogensberger said. “The X-ray data traces a unique picture that you can’t see in any other wavelength.”
Bogensberger and an international team of colleagues published their findings in The Astrophysical Journal.
In its study, the team looked at Chandra’s observations of Centaurus A from 2000 to 2022. Or, more accurately, Bogensberger developed a computer algorithm to do that. The algorithm tracked bright, lumpy features in the jet, which are called knots. By following knots that moved during the observation period, the team could then measure their speed.
The speed of one knot was particularly remarkable. In fact, it appeared to be moving faster than the speed of light because of how it moves relative to Chandra’s vantage point near Earth. The distance between the knot and Chandra shrinks almost as fast as light can travel.
The team determined the knot’s actual speed was at least 94% the speed of light. A knot in a similar location had previously had its speed measured using radio observations. That result clocked the knot with a significantly slower speed, about 80% the speed of light.
“What this means is that radio and X-ray jet knots move differently,” Bogensberger said.
And that wasn’t the only thing that stood out from the data.
For example, radio observations of knots suggested the structures closest to the black hole move the fastest. In the new study, however, Bogensberger and his colleagues found the fastest knot in a sort of middle region – not the farthest from the black hole, but not the nearest to it either.
“There’s a lot we still don’t really know about how jets work in the X-ray band. This highlights the need for further research,” Bogensberger said. “We’ve shown a new approach to studying jets and I think there’s a lot of interesting work to be done.”
For his part, Bogensberger will be using the team’s approach to examine other jets. The jet in Centaurus A is special because it’s the closest jet we know of at about 12 million light years away.
This relative proximity made it a good first option for testing and validating the team’s methodology. Features like knots become more challenging to resolve in jets that are farther away.
“But there are other galaxies where this analysis can be done,” Bogensberger said. “And that’s what I plan to do next.”
https://today.uconn.edu/2024/10/uconn-researchers-working-to-extinguish-inflammatory-fire-stroke-causes-in-the-brain/
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