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Stroke

Imaging, Research, Stanford News, Stroke, Technology

Image-interpretation software could open window of treatment for stroke

Image-interpretation software could open window of treatment for stroke

open windowRestoring blood flow to the brain quickly after a stroke is key to damage control as well as to optimal recovery. But restoring blood flow to brain tissue that is already dead can cause problems, like swelling and hemorrhage.

That makes the treatment of choice – an intravenous dose of a substance called tPA, which dissolves clots – a double-edged sword. The consensus in the medical community is that tPA is not a good idea once 4-1/2 hours have elapsed since a patient has suffered a stroke.

But the consensus is based on averages, derived from numerous studies. Clinicians have tended to treat that 4-1/2 hour time-point as analogous to a window slamming shut. Yet every stroke, and every patient who experiences one, is unique.

A new study published in the New England Journal of Medicine joins three earlier ones that show improved results when tPA administration is combined with the insertion of a device – a so-called stent retriever – that can mechanically break up clots in the brain.

Even more exciting, two of the four studies, including the new one, employed software called RAPID – designed and developed at Stanford at the instigation of Stanford neurologist Greg Albers, MD – that quickly interprets brain scans of patients and helps clinicians decide which patients will benefit from supplementing the standard intravenous tPA infusion with the stent retrieval procedure. In both of these two studies, substantial majorities of patients selected as good candidates for the combination had extremely high rates of solid recovery as measured three months after their stroke – the best results ever obtained in stroke studies.

Albers, who is also one of the co-authors of the new NEJM study, hopes to move stroke care away from the clock on the wall and instead focus on a biological clock – what the brain image shows to be going on inside this patient’s brain, now – so that each patient’s care can be individualized and optimized. It could turn out that for some patients, 4-1/2 hours after a stroke is already too late for aggressive clot-busting treatment, while for others the window remains wide open for 6, 7, 8 hours or longer.

Previously: Targeted stimulation of specific brain cells boosts stroke recovery in mice, Calling all pharmacologists: Stroke-recovery mechanism found, small molecule needed and Stanford neuroscientists uncover potential drug treatment for stroke
Photo by glasseyes view

Biomed Bites, Neuroscience, Research, Stroke, Videos

Taking the “molecular brakes” off learning

Taking the "molecular brakes" off learning

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers. 

When Carla Shatz, PhD, was a child, her grandmother suffered a stroke.

“At the time, people really couldn’t do anything for her and they didn’t understand how to give her rehab,” Shatz, a professor of biology and neurbiology, said in the video above. Shatz was sad and frustrated, but also curious: How does the brain change and recover, allowing for learning and growth?

“This research is something I’ve been working on for my entire career,” she said.

But now she and her team are starting to glean some insights into how the brain operates that could prove helpful for stroke treatments. Children learn effortlessly, but in adulthood, “molecular brakes” stymie the brain’s ability to create new connections, Shatz explained.

“If we could only take those brakes on learning off, we could restore learning to the amazing childlike state,” Shatz said. She and her collaborators have several ideas, ones that have shown promise in helping mice recover from stroke:

The last few years we’ve actually been able to come back to this question of stroke and address it with the knowledge of molecular mechanisms and the concept that enhancing brain plasticity and understanding how it works could actually allow for better recovery from stroke.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Science is like an ongoing mystery novel, says Stanford neurobiologist Carla Shatz, Examining the potential of creating new synapses in old or damaged brains  and Drug helps old brains learn new tricks 

Aging, Immunology, Neuroscience, Research, Stanford News, Stroke

Can immune cells’ anomalous presence in brain explain delayed post-stroke dementia?

Can immune cells' anomalous presence in brain explain delayed post-stroke dementia?

bees in the bonnetAbout every 40 seconds, someone in the United States has a stroke. About one in three of those people will eventually suffer from dementia if they live long enough, even if there’s been no initial damage to brain structures involved in memory and cognition. That’s a mystery.

In a recent study in The Journal of Neuroscience, Stanford neurologist and stroke expert Marion Buckwalter, MD, PhD, points a bony scientific finger at a major likely reason why having a stroke doubles a person’s risk of incurring dementia within the next decade.

The culprit, surprisingly, seems to be a type of normally very beneficial immune cells that under ordinary circumstances have no business being in the brain. These trespassers, called B cells, are best known for generating antibodies that fight off invading pathogens. As I wrote in my release on the new study:

The antibodies that B cells produce are normally of great value to us. They circulate throughout blood and lymph, and bind to microbial invaders, gumming up the pathogens’ nefarious schemes and marking them for destruction by other immune cells. Occasionally, B cells wrongly begin generating antibodies that bind to the body’s own healthy tissues, causing certain forms of autoimmune disease, such as rheumatoid arthritis. Rituxan, a drug approved by the Food and Drug Administration for this condition, is actually an antibody itself: Its target is a protein found on the surface of every B cell. Use of this drug depletes B cells in the body, relieving the symptoms of rheumatoid arthritis and other B-cell-mediated disorders.

The blood-brain barrier, which tightly controls what enters and what leaves the brain, can be disrupted by a stroke, permitting the anomalous appearance of B cells there. Buckwalter and her colleagues showed that in mice experiencing strokes, the affected brain region – immune-cell-free at least one week later – started filling up with B cells until, at seven and twelve weeks post-stroke, there were “tons” of them, she told me. Around the same time, these mice started showing signs of dementia that hadn’t been at all evident a mere week after the stroke.

But in mice of a strain that is genetically incapable of producing B cells, no such cognitive loss occurred. Not only that, but giving plain old ordinary mice Rituxan five days after a stroke prevented this post-stroke dementia.

Then Buckwalter and her team looked at preserved, autopsied brain-tissue samples from people who had had stroke and dementia. Once again, they observed inordinate numbers of B cells in the majority of these brains, suggesting that humans, too, can experience late but lasting infiltration of rampaging B cells into our brains after a stroke.

So maybe giving a Rituxan-like B-cell-depleting compound to these people within that first week after their stroke could stave off dementia.

This wouldn’t by advisable for all stroke patients. You don’t want to wipe out somebody’s B cells (usually, they’re good guys) unless they are causing trouble. And, as seen in the autopsied tissue samples, not all stroke sufferers’ brains fall into that category.

But, Buckingham noted, Rituxan or something like it could work a double shift as both a therapeutic and a diagnostic. Rituxan pretty much binds only to B cells (a prelude to killing them), so tagging the drug with an imaging agent that could be picked up by, say, an MRI scan might tell clinicians which stroke patients have, or don’t have, B’s in their bonnets.

Previously: Targeted stimulation of specific brains cells boosts stroke recovery in mice, Calling all pharmacologists: Stroke-recovery mechanism found, small molecule needed and Brain sponge: Stroke treatment may extend time to prevent brain damage
Photo by _annamo

Aging, Neuroscience, Stanford News, Stroke, Videos

Bio-X undergraduate student finds direction through research

Bio-X undergraduate student finds direction through research

Richie Sapp arrived to Stanford as an undergraduate already interested in studying neuroscience. After talking with several faculty members, he ended up working in the lab of Carla Shatz, PhD, director of Stanford Bio-X.

I interviewed Sapp recently for a series of stories I was working on about undergraduate research opportunities at Stanford. He had participated in a terrific summer program run by Bio-X. I was struck by a few things when we talked, one of which was Sapp’s sincere interest in helping people. He had grown up with a twin brother who had been born with hydrocephaly and as a result had learning delays and is on the autism spectrum. That experience shaped his interest in helping people with similar challenges.

Sapp said that through his experience in the lab he got more out of his undergraduate classes and learned a lot about where he wants to go with his life. He loves the research and discovery, but also wants to go the medical school before pursuing research. Without the experience provided by the Bio-X summer program he might not have known which direction to go.

“The experience of designing experiments and seeing a project through to the end is going to be important for me in whatever I do next,” he said.

Here is the full profile about Sapp, with more about his research experiences.

Previously: Drug helps old brains learn new tricks, and heal

Mental Health, Neuroscience, Stroke

Neurosciences get the limelight at Davos

Neurosciences get the limelight at Davos

IMG_0887Four faculty from the Stanford Neurosciences Institute have been in Davos for the past few days attending the World Economic Forum along with world leaders and economic illuminati. They were invited to form a panel about the recently announced Big Ideas in Neuroscience, which is a novel way of bringing faculty together around health challenges like stroke, neurodegenerative disease and mental health conditions. If this approach is successful it could help ease the crippling economic and emotional costs of those diseases.

Amit Etkin, MD, PhD, emailed me from the conference that attendees seem to be very excited and focused on the sessions, with lines out the door of people waiting for seating. The entire panel included Etkin, who co-leads a mental health team, Marion Buckwalter, MD, PhD, who leads a stroke collaboration, and Tony Wyss-Coray, PhD, and Anne Brunet, PhD, who are both part of the neurodegenerative disease team.

Tomorrow at 6 a.m. Pacific Time both Etkin and Wyss-Coray will be webcast live in conversation with NPR correspondent Joe Palca. That webcast is available on the World Economic Forum website.

Previously: Neuroscientists dream big, come up with ideas for prosthetics, mental health, stroke and more, Stanford expert responds to questions about brain repair and the future of neuroscience

Aging, Neuroscience, Stanford News, Stroke, Videos

Examining the potential of creating new synapses in old or damaged brains

Examining the potential of creating new synapses in old or damaged brains

Synapses are the structures in the brain where neurons connect and communicate with each other. Between early childhood and the beginning of puberty, many of these connections are eliminated through a process called “synaptic pruning.” Stroke, Alzheimer’s disease, and traumatic brain injury can also cause the loss of synapses. But what if new synapses could be created to repair aging or damaged brains?

Stanford neurobiologist Carla Shatz, PhD, addresses this question in the above Seattle+Connect video. In the lecture, she discusses the possibility of engaging the molecular and cellular mechanisms that regulate critical developmental periods to regrow synapses in old brains. Watch the video to learn how advances at the neural level around a novel receptor, called PirB, have implications for improving brain plasticity, learning, memory and neurological disorders.

Previously: Drug helps old brains learn new tricks, and heal, Cellular padding could help stem cells repair injuries and Science is like an ongoing mystery novel, says Stanford neurobiologist Carla Shatz and “Pruning synapses” and other strides in Alzheimer’s research

Aging, Neuroscience, Stanford News, Stroke, Videos

Stanford expert responds to questions about brain repair and the future of neuroscience

Stanford expert responds to questions about brain repair and the future of neuroscience

One cool thing about being at Stanford is access to really, really smart people. Case in point, I get to work with William Newsome, PhD, who, in addition to doing really interesting neuroscience research, co-leads the group that made recommendations to the national BRAIN Initiative, and also directs the new Stanford Neurosciences Institute. He has a lot of insight into the state of neuroscience, where the field is headed, and what challenges scientists face in trying to better understand the brain and develop new therapies.

Newsome recently participated in an Open Office Hours, in which Stanford faculty take questions through Facebook, essentially opening their office doors to anyone with questions. He later recorded answers to those questions in the video above.

In addition to the full- length video, we’ve been posting short excerpts on Facebook. In this clip, Newsome discusses the dynamic nature of our brain’s connections. As he explains, the brain can switch connectivity to let us have one set of behaviors with our boss and another with our spouse.

In today’s installment, Newsome discusses efforts to repair nerves that are damaged in stroke, spinal cord injuries, traumatic brain injuries or other conditions. Stroke is of particular interest right now – the Neurosciences Institute that Newsome leads recently announced the creation of an interdisciplinary consortium at Stanford focused on stroke as one of their Big Ideas in Neuroscience.

In that segment, Newsome points out that nerves of our arms or legs, the so-called peripheral nervous system, can regrow if they get damaged. If you cut your finger, the nerves regrow. If you have a stroke or damage your spinal cord, the nerves don’t regrow. Newsome said:

What’s the difference between the central nervous system and the peripheral nervous system such that the central nervous system does not regrow most of the time yet the peripheral nervous system does? … When we get that knowledge the hope is that we’ll be able to set the conditions right for regrowth when there’s an injury and we’ll actually be able to help people recover function.

Previously: Deciphering “three pounds of goo” with Stanford neurobiologist Bill Newsome, Open Office Hours: Stanford neurobiologist taking your questions on brain research, Neuroscientists dream big, come up with ideas for prosthetics, mental health, stroke and more, Co-leader of Obama’s BRAIN Initiative to direct Stanford’s interdisciplinary neuroscience institute and Brain’s gain: Stanford neuroscientist discusses two major new initiatives

Aging, Neuroscience, Research, Stanford News, Stroke

Drug helps old brains learn new tricks, and heal

Drug helps old brains learn new tricks, and heal

shatz_news

Our brains go through remarkably flexible periods in childhood when they can form new connections in a flash and retain information at a rate that leaves adults (or at least me) both impressed and also deeply jealous.

Now neurobiologist Carla Shatz, PhD, has developed a drug that at least in mice can briefly open that window for making new connections in the adult brain. It works as a sort of decoy, tricking other molecules in the cell into binding to it rather than to the “real” protein on the neuron’s surface. Without the bound molecules, the protein on the neuron’s surface releases its brake on synapse formation.

There are still a number of hurdles to overcome before the drug could work in people. The human version of the protein she studied is slightly different than the mouse version, and she had to inject the drug directly into the mouse brain. She would need to find a way of delivering the drug as a pill before it could be useful in people.

Despite those hurdles, the possibilities are exciting. From a story I wrote on the possible uses for such a drug, which she had tested in a form of blindness in mice:

This model that the team studied in mice directly applies to forms of blindness in people. Children who are born with cataracts need to have the problem repaired while the vision processing region of the brain is still able to form new connections with the eyes. “If the damage isn’t repaired early enough then it’s extremely difficult if not impossible to recover vision,” Shatz said.

If a version of the decoy protein could work in people, then kids born with cataracts in countries with limited access to surgery could potentially have their cataracts removed later, receive a drug, and be able to see. Similarly, the window could be briefly opened to help people recover from stroke or other conditions.

Previously: How villainous substance starts wrecking synapses long before clumping into Alzheimer’s plaques, “Pruning synapses” and other strides in Alzheimer’s research
Image, which shows neurons of the visual system in mice that have formed new connections, courtesy of the Shatz lab

Addiction, Bioengineering, Mental Health, Neuroscience, Stanford News, Stroke

Neuroscientists dream big, come up with ideas for prosthetics, mental health, stroke and more

Neuroscientists dream big, come up with ideas for prosthetics, mental health, stroke and more

lightbulbs

So there you are, surrounded by some of the smartest neuroscientists (and associated engineers, biologists, physicists, economists and lawyers) in the world, and you ask them to dream their biggest dreams. What could they achieve if money and time were no object?

That’s the question William Newsome, PhD, asked last year when he became director of the new Stanford Neurosciences Institute. The result is what he calls the Big Ideas in Neuroscience. Today the institute announced seven Big Ideas that will become a focus for the institute, each of which includes faculty from across Stanford schools and departments.

In my story about the Big Ideas, I quote Newsome:

The Big Ideas program scales up Stanford’s excellence in interdisciplinary collaboration and has resulted in genuinely new collaborations among faculty who in many cases didn’t even know each other prior to this process. I was extremely pleased with the energy and creativity that bubbled up from faculty during the Big Ideas proposal process. Now we want to empower these new teams to do breakthrough research at important interdisciplinary boundaries that are critical to neuroscience.

The Big Ideas are all pretty cool, but I find a few to be particularly fascinating.

One that I focus on in my story is a broad collaboration intended to extend what people like psychiatrist Robert Malenka, MD, PhD, and psychologist Brian Knutson, PhD, are learning about how the brain makes choices to improve policies for addiction and economics. Keith Humphreys, PhD, a psychiatry professor who has worked in addiction policy and is a frequent contributor to this blog, is working with this group to help them translate their basic research into policy.

Another group led by bioengineer Kwabena Boahen, PhD, and ophthalmologist E.J. Chichilnisky, PhD, are working to develop smarter prosthetics that interface with the brain. I spoke with Chichilnisky today, and he said his work develop a prosthetic retina is just the beginning. He envisions a world where we as people interface much more readily with machines.

Other groups are teaming up to take on stroke, degenerative diseases, and mental health disorders.

One thing that’s fun about working at Stanford is being able to talk with really smart people. It’s even more fun to see what happens when those smart people dream big. Now, they face the hard work of turning those dreams into reality.

Previously: This is your brain on a computer chip, Dinners spark neuroscience conversation, collaboration and Brain’s gain: Stanford neuroscientist discusses two major new initiatives
Photo by Sergey Nivens/Shutterstock

Bioengineering, Cardiovascular Medicine, Neuroscience, Research, Stanford News, Stroke

Targeted stimulation of specific brain cells boosts stroke recovery in mice

Targeted stimulation of specific brain cells boosts stroke recovery in mice

big blue brainThere are 525,949 minutes in a year. And every year, there are about 800,000 strokes in the United States – so, one stroke every 40 seconds. Aside from the infusion, within three or four hours of the stroke, of a costly biological substance called tissue plasminogen activator (whose benefit is less-than-perfectly established), no drugs have been shown to be effective in treating America’s largest single cause of neurologic disability and the world’s second-leading cause of death. (Even the workhorse post-stroke treatment, physical therapy, is far from a panacea.)

But a new study, led by Stanford neurosurgery pioneer Gary Steinberg and published in Proceedings of the National Academy of Sciences, may presage a better way to boost stroke recovery. In the study, Steinberg and his colleagues used a cutting-edge technology to directly stimulate movement-associated areas of the brains of mice that had suffered strokes.

Known as optogenetics – whose champion, Stanford psychiatrist and bioengineer Karl Deisseroth, co-authored the study – the light-driven method lets investigators pinpoint a specific set of nerve cells and stimulate only those cells. In contrast, the electrode-based brain stimulation devices now increasingly used for relieving symptoms of Parkinson’s disease, epilepsy and chronic pain also stimulate the cells’ near neighbors.

“We wanted to find out whether activating these nerve cells alone can contribute to recovery,” Steinberg told me.

As I wrote in a news release  about the study:

By several behavioral … and biochemical measures, the answer two weeks later was a strong yes. On one test of motor coordination, balance and muscular strength, the mice had to walk the length of a horizontal beam rotating on its axis, like a rotisserie spit. Stroke-impaired mice [in which the relevant brain region] was optogenetically stimulated did significantly better in how far they could walk along the beam without falling off and in the speed of their transit, compared with their unstimulated counterparts. The same treatment, applied to mice that had not suffered a stroke but whose brains had been … stimulated just as stroke-affected mice’s brains were, had no effect on either the distance they travelled along the rotating beam before falling off or how fast they walked. This suggests it was stimulation-induced repair of stroke damage, not the stimulation itself, yielding the improved motor ability.

Moreover, levels of some important natural substances called growth factors increased in a number of brain areas in  optogenetically stimulated but not unstimulated post-stroke mice. These factors are key to a number of nerve-cell repair processes. Interestingly, some of the increases occurred not only where stimulation took place but in equivalent areas on the opposite side of the brain, consistent with the idea that when we lose function on one side of the brain, the unaffected hemisphere can step in to help restore some of that lost function.

Translating these findings into human trials will mean not just brain surgery, but also gene therapy in order to introduce a critical light-sensitive protein into the targeted brain cells. Steinberg notes, though, that trials of gene therapy for other neurological disorders have already been conducted.

Previously: Brain sponge: Stroke treatment may extend time to prevent brain damage, BE FAST: Learn to recognize the signs of stroke and Light-switch seizure control? In a bright new study, researchers show how
Photo by Shutterstock.com

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