Simple, because NO ONE looked at the recovery protocol that Pedro Bach-y-Rita used to recover fully back in 1958 with only a partial brain! But you don't have anyone COMPETENT AT ALL, DO YOU?
Study reveals why many patients fail to recover after stroke
A clot forms. Blood flow to the brain is blocked. Starved of oxygen, neurons begin to die.
This scenario, known as an ischemic stroke, plays out in roughly 21,000 people worldwide each day, threatening them with long-term disability or even death. In recent decades, the advent of drugs and mechanical tools for removing clots has revolutionized stroke care.
Yet, even with the clot gone and the vessel clear, up to 50% of patients never recover neurologically. New research from the University of Colorado Boulder and the University of Antwerp helps explain why.
The study, published in the journal PNAS, reveals in unprecedented detail how the brain's own defense mechanisms against stroke can backfire, triggering yet more clots-micro-clots-in minor vessels, damaging tissue long after the primary culprit is gone.
The mystery behind "no reflow"
Doctors have long known that removing a stroke-causing clot cannot always restore full blood flow to the brain. But why this phenomenon, known as "no reflow," occurs has remained a mystery. (Just maybe because Capillaries that don't open due to pericytes and then there is the neuronal cascade of death in the first week)
To unravel it, Mukherjee, who studies the physics of blood flow, teamed up with senior author Frederik Denorme, an assistant professor of biology at the University of Antwerp who studies, as he puts it, "life after the clot."
"The dogma used to be that you just need to get rid of that blood clot and then all problems should be solved," said Denorme. "We now know that is not the case."
In fact, only about 1 in 10 surviving stroke patients recover completely after a stroke; 25% have minor impairments; and half have moderate to severe impairments.
To examine what, precisely, goes on in the brain after a clot is removed, the research team first turned to mice.
Using a technique called intravital microscopy, they observed in real time how blood flowed in the brain and cells behaved in the hour after the mice suffering from stroke underwent endovascular thrombectomy-a procedure in which a tool is threaded through a blood vessel to pluck out an obstructive clot.
While blood quickly started flowing again post-procedure, the researchers were stunned to see that in many mice, it flowed haphazardly, in fits and starts, even reversing course at certain points.
"We saw it happening with our own eyes. Blood that was flowing left all of a sudden flowed right and vice versa," said Denorme. "It was remarkable."
A Jekyll and Hyde protein
An even closer look revealed that, as the brain tried to divert blood around the original obstruction, tiny clots formed where the haphazard channels converged.
To drill down on why those clots formed, Mukherjee's FLOWLab recreated this scenario using computer simulations. In other research, his lab has recreated similar scenarios using a 3D artificial brain filled with fake blood.
These experiments implicated Von Willebrand Factor - a protein best known for stopping us from bleeding when we get a cut.
In its resting state, Mukherjee explained, Von Willebrand Factor is coiled up like a ball of string inside blood vessels, waiting for distress signals from the body that make it stretch out and start forming clots to stop bleeding.
In a brain experiencing a stroke, something else unfolds the ball.
"If there is some kind of fluid motion induced after the clot is removed, it can stretch out that ball into an extended thread that attracts platelets, forms new clots and blocks flow even after the original culprit clot is gone," Mukherjee said.
Meanwhile, the study showed, the brain's inflammatory response to stress interferes with safeguards that normally keep the protein's clotting efforts in check, creating what the authors call "a perfect storm" of collateral damage.
Other experiments, looking at blood from stroke patients at the University of Washington in St. Louis, suggest a similar phenomenon happens in humans too.
"We are the first to really show in this hyperacute phase of stroke what is happening with these cells inside blood vessels," said Denorme. "Seeing is believing."
More research is necessary to determine why no reflow happens in some stroke patients but not others. But the study did find that stroke patients with higher blood levels of a pro-inflammatory compound called Interleukin 6 had more overactive Von Willebrand Factor and worse long-term outcomes.
The researchers envision a day when therapeutics targeting Von Willebrand Factor, or the inflammatory compounds that exacerbate its clotting capabilities, could be given to stroke patients alongside clot-busting drugs and surgery.
Notably, several drugs targeting Von Willebrand Factor already exist and are approved for use for other disorders.
"It's early days. But now that we have a lead on what drives these micro-clots, we have a promising new avenue to explore for improving recovery," said Denorme.
Laroche, A., et al. (2026). Mechanisms of von Willebrand factor activation driving no reflow in ischemic stroke. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2610397123. https://www.pnas.org/doi/10.1073/pnas.2610397123
