Stories about: stroke

Mitigating blood vessel damage from heart attack, stroke

Mouse hearts showing the impact of a therapeutic protein fusion on blood vessel health
Imaging of mouse hearts reveals widespread tissue damage (light-colored areas) after heart attack. At far right, however, mice that were treated with an engineered, optimized ApoM protein containing S1P have better tissue recovery than untreated mice (left) and mice that were given an inactive “dud” ApoM treatment (center). Credit: Hla lab/Boston Children’s Hospital

The average human has 60,000 miles of blood vessels coursing through their body. There are a number of mechanisms the body uses to keep that vast vascular network healthy, including a tiny fat molecule, a lipid called S1P, that plays a particularly important role.

S1P receptors dot the surface of the endothelium, a layer of cells that line the inside of all the body’s blood cells. Together, these so-called endothelial cells form a barrier between the body’s circulating blood and surrounding tissue. When S1P molecules activate their receptors, it suppresses endothelial inflammation and generally helps regulate cardiovascular health.

Now, researchers led by Timothy Hla, PhD, from the Boston Children’s Hospital Vascular Biology Program, report a novel therapeutic fusion that could trigger increased S1P receptor activity and recover blood vessel health following the onset of hypertension, atherosclerosis, stroke, heart attack and other cardiovascular diseases.

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Fast-regenerating mice offer clues for stroke, spinal cord and optic nerve injury

axon regeneration CNS
The CAST mouse from Thailand–genetically distinct from most lab mice–may have the right ingredients for nerve regeneration. (Courtesy Jackson Laboratory)

Second in a two-part series on nerve regeneration. Read part 1.

The search for therapies to spur regeneration after spinal cord injury, stroke and other central nervous system injuries hasn’t been all that successful to date. Getting nerve fibers (axons) to regenerate in mammals, typically lab mice, has often involved manipulating oncogenes or tumor suppressor genes to encourage growth, a move that could greatly increase a person’s risk of cancer.

A study published online last week by Neuron, led by the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, took a completely different tactic.

Seeing little success at first, the researchers wondered whether they were working with the wrong mice.

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What can pulse pressure teach us about pediatric obesity?

pulse pressure
Subtract 68 from 100 to get a pulse pressure of 42 (Wikiphoto/Creative Commons)

Second in a two-part series on cardiovascular prevention in children. Read part 1.

Carrying too much weight is tough on the body. The dramatic rise of obesity in recent years means more and more people are confronting increased cardiovascular risk due to changes in their blood vessels, cholesterol levels, blood pressure, and blood sugar. And the problem isn’t limited to adults: Today, there are more than three times as many obese children in the U.S. than there were in the early 1970s.

However, not every person with excess weight has cardiac risk factors, and not everyone with cardiac risk factors carries excess weight. So what is the relationship between childhood obesity and cardiac risk factors later in life? What links excess weight to its consequences?

Justin Zachariah, MD, MPH, a cardiologist at Boston Children’s Hospital, was inspired to investigate these “risk factors of risk factors” when he observed a pattern in his pediatric preventive cardiology clinic. He noticed that many of his patients who were carrying excess weight did not have very high blood pressure, or hypertension.

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An IOTA of thumb control for children with cerebral palsy, hemiplegia, stroke

This child-sized device assists children with thumb movements while giving them sensory and visual feedback.
This child-sized device assists children with thumb movements while giving them sensory and visual feedback. (Image: Wyss Institute, Harvard University)
Our ability to use the thumb as an opposable digit is a critical part of what sets us apart as a species. “That’s how you’re holding a pen,” Leia Stirling, PhD, a senior staff engineer at the Wyss Institute for Biologically Inspired Engineering told me recently as we talked about the Wyss’ latest collaboration with Boston Children’s Hospital. “That’s how you hold your phone; that’s how you open a door; that’s what makes us unique.”

It’s also an ability that children who have suffered a stroke or have cerebral palsy or hemiplegia (paralysis on one side of the body) can lose or fail to develop in the first place.

Stirling, along with Hani Sallum, MS, and Annette Correia, OT, in Boston Children’s departments of Physical and Occupational Therapy, are the architects of a robotic device that may improve functional hand use. The device assists children with muscle movements, using small motors called “actuators” placed over the hand joints, while giving them sensory and visual feedback. It’s called the Isolated Orthosis for Thumb Actuation, or IOTA.

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Putting the squeeze on blood clots to stop a stroke

Blood should flow through an artery like water through a hose. The stress of a blockage can encourage clots to form, potentially resulting in a heart attack or stroke. Donald Ingber thinks the same forces could be used to help dissolve clots. (Beth Kingery/Flickr)

Grab a garden hose. Put your thumb over the end, but not all the way, and turn the water on. What happens? The water coming out of the hose gets squeezed as it tries to push past your thumb, putting a lot of force on the molecules in the water and making a big spray.

Now do the same thing with an artery: Partially block it with a clot and let blood flow through it. In this case, the force you’ve created in the artery could be lethal—creating fertile ground for blood clots that could lead to a stroke or heart attack.

But what if that combination of force and pressure could be used to stop something like a stroke instead? What if it could release a clot-dissolving drug on the spot? Donald Ingber, MD, PhD, a member of Boston Children’s Hospital’s Vascular Biology Program, had wondered that for many years. To find out, Ingber, who also directs the Wyss Institute for Biologically Inspired Engineering at Harvard, had his team start with a simple question: How do clots form?

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Curbing stroke’s inflammatory damage: A new target

Brain MRIs from mice after stroke. Mice lacking Hv1 (right panels) had a much smaller volume of infarcted tissue than normal mice. Hv1 can also be blocked chemically.

Whether it’s in adults or in children with clotting disorders or other conditions such as sickle-cell disease, a stroke can be likened to an atomic bomb. Just as ongoing radiation can do more damage than the bomb itself, the secondary damage of a stroke can devastate the brain.

In an ischemic stroke, accounting for nearly 90 percent of all stroke cases, it happens like this: When vessels supplying blood and oxygen to the brain are blocked by a narrowing or a clot, immune cells in the brain sense the low-oxygen conditions, suspect an invading organism and try to kill it by producing molecules known as reactive oxygen species or ROS’s. These, unfortunately, have an inflammatory effect that actually damages the brain further, injuring and killing neurons.

“Stroke produces inflammation, and that’s one of the main things people have been after in trying to reduce stroke damage,” says David Clapham, MD, PhD, chief of the Basic Cardiovascular Research Laboratories at Boston Children’s Hospital.

Right now there’s nothing that can do this. Most existing stroke drugs are aimed at preventing the stroke or dissolving blood clots once the stroke is happening – but they can’t deal with the aftermath.

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Battling rising hypertension in children: 5 tools

FDR (here signing the Declaration of War against Japan, 1941) died from a stroke caused by years of hypertension. Millions of U.S. children could meet the same fate – unless we act now.

While many of us recall that President Franklin Delano Roosevelt had polio, few remember that he died in 1945 from another cause: stroke. The sentiment of his physician — that it “had come out of the clear sky” — reflected the prevailing view that heart attack and stroke were bolts from the blue that doctors could act on only after the event.

But a few mavericks challenged this “salvage” paradigm, establishing the Framingham Heart Study in 1948 to identify predictors of cardiovascular events. One leading maverick, Dr. William Kannel, who passed away last month, coined the term “risk factors” to describe these predictors. Acting on the insight that controlling risk factors could prevent cardiovascular disease saved the lives of more than 150,000 Americans from heart disease alone between 1980 and 2000.

Judging by the surviving medical records, Roosevelt’s stroke may have been preventable with treatment for one such risk factor, hypertension. How different would the world have been had his persistent high blood pressure been treated?

The world is different now, not all for the better. High blood pressure has been attacking more and more children over the last 30 years,

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