Discovery could aid understanding of brain disruptions that occur in stroke, other disorders.

Johannes Hell, UC Davis

When brain cells are overwhelmed by an influx of too many calcium molecules, they shut down the channels through which these molecules enter the cells. Until now, the “stop” signal mechanism that cells use to control the molecular traffic was unknown.

In the new issue of the journal Neuron, UC Davis Health System scientists report that they have identified the mechanism. Their findings are relevant to understanding the molecular causes of the disruption of brain functioning that occurs in stroke and other neurological disorders.

“Too much calcium influx clearly is part of the neuronal dysfunction in Alzheimer’s disease and causes the neuronal damage during and after a stroke. It also contributes to chronic pain,” said Johannes W. Hell, professor of pharmacology at UC Davis. Hell headed the research team that identified the mechanism that stops the flow of calcium molecules, which are also called ions, into the specialized brain cells known as neurons.

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UCLA, partners to conduct two community-based trials of stroke-prevention interventions.

Barbara Vickrey, UCLA

UCLA researchers and their partners across Los Angeles County have been awarded an $11 million federal grant to fund research on community-based interventions aimed at reducing the higher rates of stroke and death from stroke among disadvantaged Hispanics, African Americans and Asian Americans.

Research has shown that stroke risk can be substantially lowered by increasing physical activity, controlling blood pressure, adopting a healthy diet, quitting smoking, lowering cholesterol and, for certain individuals, taking medication like aspirin.

However, the underserved populations targeted by this research program are frequently prevented from achieving these health goals by a variety barriers, including a lack of transportation for doctor visits, an inability to afford medication, insufficient knowledge about how to change their lifestyle, living in neighborhoods where infrastructure or safety concerns prevent walking, and an inability to read food labels in English, among others.

The Los Angeles Stroke Prevention/Intervention Research Program in Health Disparities is a multipartner research center funded by the National Institutes of Health that will conduct two randomized, controlled, community-based trials of stroke-prevention interventions. One will measure how much the risk of recurrent stroke is lowered by teaming community health workers with physicians and nurses at Los Angeles medical centers serving low-income populations.

“These community health workers will conduct home visits to outreach to patients with a recent stroke,” said the research center’s director, Dr. Barbara Vickrey, vice chair and professor of neurology at the David Geffen School of Medicine at UCLA. “They will use mobile health technology to help them educate and empower these patients to make changes in their diet and physical activity and to promote the use of home blood-pressure monitors and medications that substantially lower the risk of another stroke.”

A second trial will assess the impact and sustainability of a culturally tailored behavioral intervention designed to provide stroke risk–factor education and increase physical activity, primarily walking. This program will be delivered by staff at senior centers serving African American, Latino, Chinese and Korean communities in Los Angeles and is designed to be self-sustained after the study is over.

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Brain imaging, stroke risk assessment detect the signs before symptoms appear.

Brain scan of patient with mild cognitive impairment (MCI)

UCLA researchers have used a brain-imaging tool and stroke risk assessment to identify signs of cognitive decline early on in individuals who don’t yet show symptoms of dementia.

The connection between stroke risk and cognitive decline has been well established by previous research. Individuals with higher stroke risk, as measured by factors like high blood pressure, have traditionally performed worse on tests of memory, attention and abstract reasoning.

The current small study demonstrated that not only stroke risk, but also the burden of plaques and tangles, as measured by a UCLA brain scan, may influence cognitive decline.

The imaging tool used in the study was developed at UCLA and reveals early evidence of amyloid beta “plaques” and neurofibrillary tau “tangles” in the brain — the hallmarks of Alzheimer’s disease.

The study, published in the April issue of the Journal of Alzheimer’s Disease, demonstrates that taking both stroke risk and the burden of plaques and tangles into accout may offer a more powerful assessment of factors determining how people are doing now and will do in the future.

“The findings reinforce the importance of managing stroke risk factors to prevent cognitive decline even before clinical symptoms of dementia appear,” said first author David Merrill, an assistant clinical professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA.

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Targeting small intestine may be new strategy to prevent diet-induced atherosclerosis.

Alan Fogelman, UCLA

UCLA researchers have genetically engineered tomatoes to produce a peptide that mimics the actions of good cholesterol when consumed.

Published in the April issue of the Journal of Lipid Research and featured on the cover, their early study found that mice that were fed these tomatoes in freeze-dried, ground form had less inflammation and plaque build-up in their arteries.

“This is one of the first examples of a peptide that acts like the main protein in good cholesterol and can be delivered by simply eating the plant,” said senior author Dr. Alan M. Fogelman, executive chair of the department of medicine and director of the atherosclerosis research unit at the David Geffen School of Medicine at UCLA. “There was no need to isolate or purify the peptide — it was fully active after the plant was eaten.”

After the tomatoes were eaten, the peptide surprisingly was found to be active in the small intestine but not in the blood, suggesting that targeting the small intestine may be a new strategy to prevent diet-induced atherosclerosis, the plaque-based disease of the arteries that can lead to heart attacks and strokes.

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Using brain scans to ID which patients might be best candidates for embolectomy didn’t lead to better outcomes for those patients.

Reza Jahan, UCLA

When someone has a stroke, time equals brain. The longer a stroke is left untreated, the more brain tissue is lost. Since the only proven treatment — a clot-busting drug — works in less than half of patients, stroke physicians had high hopes for a mechanical device that could travel through the blocked blood vessel to retrieve or break up the clot, restoring blood flow to the brain.

But in a recently completed multisite trial in which UCLA served as the clinical coordinating center, researchers found there was no overall recovery benefit to patients treated with clot-removal (embolectomy) devices, compared with standard post-stroke care, which includes monitoring blood pressure and ensuring the brain is receiving oxygen.

The study also found that using brain scans to identify which patients might be the best candidates for embolectomy did not lead to better outcomes for those patients.

The study was sponsored by the National Institutes of Health, and the results appeared in the March 7 edition of the New England Journal of Medicine.

Treating an acute stroke is always a race against the clock, and the first step is to immediately determine, through the use of a CT or MRI brain scan, whether the stroke is a hemorrhagic stroke, caused by a burst blood vessel, or the much more common ischemic stroke, caused by a clot blocking the flow of blood in a blood vessel.

With an ischemic stroke, the clot-dissolving drug called tissue plasminogen activator, or tPA, is approved for use within three hours of the onset of stroke symptoms. But most stroke victims don’t arrive at the hospital within that time frame, and even then, tPA may simply not work. Patients who don’t respond to tPA then receive standard post-stroke care, or they may be considered for an embolectomy.

The MR RESCUE (Mechanical Retrieval and REcanalization of Stroke Clots Using Embolectomy) trial sought to determine if imaging the brain to see how much stroke damage has already occurred could identify which patients might be the best candidate for this procedure.

The trial, which began in 2004 and involved 22 sites in the U.S., included 118 patients (average age 65.5) who were treated within eight hours of experiencing an ischemic stroke. All the patients underwent a CT or MRI brain-imaging scan before treatment.

Drawing on information from the scans, the investigators divided the patients into two groups. Patients with a favorable treatment pattern had only a small area of infarct (dead tissue) and a large area of threatened but salvageable brain tissue (called penumbral tissue). Patients with an unfavorable pattern already had a large area of infarct or a small area of penumbral tissue.

Patients from both of these groups were randomly assigned either to receive the standard medical treatment or to have their clot removed by the MERCI Retriever (a tiny corkscrew-like device developed at UCLA that “grabs” clots) or the Penumbra System (a device that sucks clots out). Both devices work by inserting a catheter through the patient’s groin to the blocked brain artery.

The hope was that by quickly removing the clot, blood would be restored to the penumbral tissue, thereby saving it. But the results showed that the level of disability 90 days after suffering a stroke was no different between those patients who underwent the clot-removal procedure and those who received standard care. Rates of death and bleeding in the brain were also the same. In addition, there was no difference between the group in which brain scans showed significant amounts of salvageable brain tissue and those with only a small area of penumbral tissue.

“We found no data showing that imaging could help select patients for treatment, nor did we show an overall benefit of performing an intervention to physically remove the clot,” said Dr. Reza Jahan, co-principal investigator for the trial, an associate professor of interventional neuroradiology and a member of the UCLA Stroke Center. “So that was disappointing. On the other hand, there are new devices that open up vessels better and faster, and with fewer complications, than the first-generation devices used in our trial.”

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Designation recognizes center’s commitment to quality care for patients.

UCLA Stroke Center

The UCLA Stroke Center has been certified as a comprehensive stroke center by the Joint Commission and the American Heart Association/American Stroke Association. The center, part of UCLA Health and the UCLA Department of Neurology, is one of the first 10 stroke centers in the nation to receive the prestigious designation.

The certification, which confirms that the UCLA Stroke Center has met the highest national standards for safety and quality of care, further enhances the center’s national reputation as an innovator in clinical care.

“This is a true team effort, reflecting the efforts of over 200 physicians, nurses, therapists, pharmacists and technologists at the UCLA Stroke Center and spanning all of UCLA Health.” said Dr. Jeffrey Saver, the center’s director and a professor of neurology at the David Geffen School of Medicine at UCLA. “It is a reflection of our team’s sustained, collective commitment to saving the lives of our stroke patients.”

The Joint Commission, an independent, not-for-profit organization that accredits and certifies more than 19,000 health care organizations and programs in the United States, conducted a rigorous on-site review at UCLA, collecting data and evaluating the center’s performance based on the commission’s requirements for the certification designation.

The commission now certifies two levels of stroke care, “primary” and “comprehensive.” Comprehensive stroke centers offer the highest level of care, including neuro-intensive care units, complex neurosurgical interventions, and advanced brain and blood-vessel imaging.

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UC San Diego neurosurgeon specializes in procedure to reverse muscle paralysis.

After four years of confinement to a wheelchair, Rick Constantine, 58, is now walking again after undergoing an unconventional surgery at UC San Diego Heath System to restore the use of his leg. Neurosurgeon Justin Brown, M.D., performed the novel 3-hour procedure.

“Following a car crash, Mr. Constantine had a brain stem stroke that caused paralysis on the right side of his body.  His leg muscles became so severely spastic that he could not walk,” said Brown, director of the Neurosurgery Peripheral Nerve Program at UC San Diego Health System. “Our team performed a delicate surgery to reduce input from the nerves that were causing the muscles to over contract to the point of disability.”

“After my injury, I was told I would never walk again. All I could to was move from my wheelchair to my bed or a chair,” said Constantine, a former NASCAR crew member. “After surgery with Dr. Brown, I could put my foot flat on the ground to walk. With physical therapy, everything just gets better and better. I’m a firm believer in never giving up.”

Prior to surgery, Constantine underwent botox treatments and physical therapy in an attempt to restore the use of his leg. The results were positive but minimal. An additional nerve conduction study, called an electromyogram (EMG), identified the muscles causing the dysfunction.

Justin Brown, UC San Diego

“When all other options did not produce satisfying results, we opted for surgery,” said Brown. “With the EMG, we identified the over-excited nerves that needed to be downgraded. Mr. Constantine had surgery on a Friday and within days was in physical rehabilitation. Two weeks later he was walking without a walker and has even completed a 1-mile race without assistance.”

The surgery, called a selective peripheral neurotomy, is a procedure performed under a microscope.  Brown makes an incision behind the knee to reach the tibial nerve. He then selectively trims back the troublesome nerve branches by up to 80 percent.  Cutting the nerve reduces the “noise” being relayed back to the spinal cord which causes the spasticity.

Brown, who also serves as co-director of the Center for Neurophysiology and Restorative Neurology at UC San Diego Health System, said the advantage to this approach is that the muscle is preserved and there is no need to cut or lengthen the tendon.

“Depending on the specific patient and their medical history, selective peripheral neurotomy may be appropriate for patients with brain and spinal cord injury from strokes or tumors, cerebral palsy or multiple sclerosis.”

No special post-operative care is required as the sutures are absorbable. Rehabilitation can begin 72 hours after the procedure.

Constantine underwent physical therapy at VIP NeuroRehabilitation Center in San Diego.

The surgery, seldom performed in the United States, is more common in France and Japan. Brown has performed this surgery on six patients. Patients requiring information on this procedure should call (858) 657-7000.

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UCSF study looks at impact of salty foods on heart attack and stroke rates over 10 years.

Pam Coxson, UC San Francisco

Hundreds of thousands of lives could be saved over 10 years if Americans reduced their sodium consumption to the levels recommended in federal guidelines, according to a new study by researchers at UC San Francisco, Harvard Medical School and Simon Fraser University in Canada.

Described this week in the journal Hypertension, the study emerged from a workshop convened last year by the U.S. Centers for Disease Control and Prevention (CDC), which sought to quantify the health benefits of population-wide sodium reduction.

The CDC brought together groups of scientists from the three universities, who each used completely different computer models to estimate how lowering sodium would save lives – largely by reducing the number of heart attacks and strokes. All three models found consistent, substantial benefits of reducing U.S. sodium consumption from the current level of intake to a level close to the upper limit of the federal guideline of 2,300 mg/day in the following ways:

• Immediately reducing sodium intake to the current upper limit of the guidelines would save 500,000 to 850,000 lives over the next 10 years.
• Gradually reducing sodium intake through processed or restaurant-prepared foods by 4 percent per year over 10 years would still yield substantial health benefits, saving 280,000 to 500,000 lives over a decade.

“No matter how we look at it, the story is the same – there will be huge benefits in reducing sodium,” said Pam Coxson, Ph.D., a UCSF mathematician and the lead author on the paper who performed one of the three analyses. Coxson is based at the UCSF Center for Vulnerable Populations, located at the San Francisco General Hospital and Trauma Center (SFGH).

The overall average sodium consumption in the United States has been estimated at 3,500 mg/day, well above the upper limit of 2,300 mg recommended by federal agencies and the Institute of Medicine. The average American male consumes even more – about twice as much sodium as recommended.

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Minimally invasive surgery may benefit patients previously deemed hopeless.

Paul Vespa, UCLA

A new endoscopic surgical procedure has been shown to be safer and to result in better outcomes than the current standard medical treatment for patients who suffer strokes as a result of brain hemorrhages, UCLA neurosurgeons have announced.

The findings from their potentially groundbreaking, randomized, controlled phase 2 clinical trial, which was conducted at multiple medical centers, were presented last week at the International Stroke Conference in Honolulu.

“These exciting results offer a glimmer of hope for a condition that most doctors have traditionally considered hopeless,” said principal investigator Dr. Paul Vespa, professor of neurosurgery at the David Geffen School of Medicine at UCLA and director of the neurocritical care program at Ronald Reagan UCLA Medical Center. “That is a big deal in medicine.”

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He was treated at UC Davis Medical Center after an ischemic stroke.

Larry Vanderhoef

UC Davis Chancellor emeritus Larry Vanderhoef was discharged from UC Davis Medical Center today (Dec. 27) after nearly four weeks of acute rehabilitation for a Dec. 1 ischemic stroke. He will continue to work with specialists as an outpatient to maintain and improve skills.

“Dr. Vanderhoef has responded well to rehabilitation and has regained much of the strength he lost on the right side of his body,” said Cassie Spalding-Dias, an assistant professor of physical medicine and rehabilitation and director of inpatient therapy at UC Davis. “Rehabilitation is an ongoing process, and we expect him to improve as his body continues to heal over the next year.”

A stroke, or “brain attack,” occurs when blood circulation to the brain fails, causing some brain cells to die from decreased blood flow and the resulting lack of oxygen. An ischemic stroke occurs when a blockage stops the flow of blood to the brain. It is the most frequent cause of stroke, responsible for about 80 percent of all strokes in the U.S. Rehabilitation helps individuals relearn skills that were lost when brain cells died. It includes a wide range of therapies that provide carefully directed, well-focused, repetitive practice — the same kind of practice used by all people when they learn a new skill such as playing the piano or pitching a baseball.

“I’m glad to be getting back home and am thankful for the excellent care that I received from the nurses and rehabilitation team at UC Davis,” Vanderhoef said. “I’m eager to pick up where I left off in the office and to be back in my seat at the Mondavi Center and at our men’s and women’s basketball games. I’m getting better, day by day and bit by piece. I am definitely on my way back!”

According to the Centers for Disease Control and Prevention, nearly 800,000 strokes occur in the United States each year. Recognizing the following signs of stroke and contacting 9-1-1 immediately can lower the risk of death and disability:

• Numbness or weakness of the face, arm or leg, especially on one side of the body
• Confusion, trouble speaking or difficulty understanding
• Trouble seeing in one or both eyes
• Trouble walking, dizziness or loss of balance and coordination
• Severe headache with no known cause.

Spalding-Dias emphasizes that treatment options are available for stroke when symptoms are identified and treated early.

“Time is brain,” Spalding-Dias said. “Rapid, early treatment can prevent long-term damage and offers the best chance of recovery for acute ischemic stroke patients.”

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UC San Diego study shows that blocking a single blood vessel can impair cognitive function.

Blocking a single tiny blood vessel, like the one highlighted in yellow, can damage brain tissue and cause a change in behavior. The image depicts the vessels in a cubic millimeter of cerebral cortex.

Blocking a single tiny blood vessel in the brain can harm neural tissue and even alter behavior, a new study from the University of California, San Diego, has shown. But these consequences can be mitigated by a drug already in use, suggesting treatment that could slow the progress of dementia associated with cumulative damage to minuscule blood vessels that feed brain cells. The team reports their results in the Dec. 16 advance online edition of Nature Neuroscience.

“The brain is incredibly dense with vasculature. It was surprising that blocking one small vessel could have a discernible impact on the behavior of a rat,” said Andy Y. Shih, lead author of the paper who completed this work as a postdoctoral fellow in physics at UC San Diego. Shih is now an assistant professor at the Medical University of South Carolina.

Working with rats, Shih and colleagues used laser light to clot blood at precise points within small blood vessels that dive from the surface of the brain to penetrate neural tissue. When they looked at the brains up to a week later, they saw tiny holes reminiscent of the widespread damage often seen when the brains of patients with dementia are examined as a part of an autopsy.

These micro-lesions are too small to be detected with conventional MRI scans, which have a resolution of about a millimeter. Nearly two dozen of these small vessels enter the brain from a square millimeter area of the surface of the brain.

“It’s controversial whether that sort of damage has consequences, although the tide of evidence has been growing as human diagnostics improve,” said David Kleinfeld, professor of physics and neurobiology, who leads the research group.

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“He is doing quite well,” says his UC Davis attending physician.

UC Davis Chancellor emeritus Larry Vanderhoef

Chancellor emeritus Larry Vanderhoef is making good progress in his recovery from a Dec. 1 stroke, according to his UC Davis Medical Center physicians.

“He is doing quite well,” said attending physician Cassie Spalding-Dias, an assistant professor of physical medicine and rehabilitation and director of inpatient therapy at UC Davis. “There is no sign of cognitive impairment. His right side has weakness, but we’re seeing encouraging signs of improvement. And his speech is good — strongest in the morning and a little softer and slower at night. We anticipate that he will make a strong recovery.”

The chancellor emeritus is expected to continue acute rehabilitation for the next two to three weeks, followed by outpatient therapies when discharged.

“I’m on my way back,” Vanderhoef said. “I’d never anticipated such a first-hand tour of our rehab center. But I’m mightily impressed — and awfully grateful. I’m thankful, too, for the many good wishes I’ve received these last few days. They mean lots.”