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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

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

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Neuroscience, Stanford News, Stroke, Surgery, Videos

Raising awareness of moyamoya disease

Raising awareness of moyamoya disease

Today isn’t just May 6, it’s also World Moyamoya Day. Well, not officially – but one patient is trying to change that.

Moyamoya, a rare cerebrovascular disease is often overlooked by neurologists, and its symptoms confused with those of chronic migraines. Tara MacInnes spent most of her childhood suffering from excruciatingly painful headaches and bouts of numbness and tingling in her hands, face and legs. Like many others with moyamoya disease, these episodes were overlooked by her pediatric neurologists. By age 16, when an especially bad episode led to an MRI and eventually a correct diagnosis, both sides of her brain had already suffered damage from strokes.

But MacInnes was lucky: She happened to live close to Stanford, where Gary Steinberg, MD, PhD, one of the world’s leading experts on moyamoya treatment, practiced. And like many patients, what MacInnes needed was more than just surgery – she needed a sense of belonging and the ability to interact with others who had gone through a similar experience.

Shortly after her surgery here MacInnes began volunteering at the Stanford Moyamoya Center, talking with patients and their families. The more she met with people, the quicker she realized it wasn’t just the general public that didn’t know much about the disease, but that many medical professionals had never heard of it. Now, 10 years after her successful surgery, MacInnes has become a devoted advocate and is determined to raise awareness about the disease; you can sign her petition to help spread the word and make World Moyamoya Day official.

Previously: How patients use social media to foster support systems, connect with physicians

Stanford News, Stroke, Technology

Using personal robots to overstep disability

The current issue of STANFORD magazine profiles an alumnus of note, Henry Evans, MBA, a former startup CFO who went on to become a TED speaker, robotics tester and advocate for disability rights. At 40, in 2002, Evans became mute and paralyzed after experiencing a stroke-like attack, and since then he has regained the ability to move his head and one finger on his left hand.

The magazine piece describes how Evans has found ways to work wonders within limitations, including using eye movements, a headtracking device and a computer to communicate and to execute household tasks. It also details his collaboration with Charlie Kemp, PhD, director of the Healthcare Robotics Lab at Georgia Institute of Technology; the Menlo Park robotics research laboratory Willow Garage; and Chad Jenkins, PhD, an associate professor of computer science at Brown University to test a personal robot called PR2.

Evans told STANFORD magazine:

“From a distance, all humans are disabled,” Henry notes. “As humans, we adapted to our environment through evolution. We developed sight and hearing and speech. Yet these adaptations are quite limited. We can’t run faster than about 25 miles per hour. We can’t fly. We can’t stay underwater forever and we can’t be in more than one place at the same time. All humans are limited by nature in many ways.

“Now, I may have lost a few of the natural adaptations which evolution afforded me, but I have adapted to these limitations, often in a way similar to how you have adapted to nature’s limitations. For example, I use a wheelchair to increase my mobility. You use a bike. You use a keyboard and mouse, I use a headtracker and a clicker to operate a computer.”

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Immunology, Neuroscience, Pain, Research, Stanford News, Stroke

Another big step toward building a better aspirin tablet

Another big step toward building a better aspirin tablet

big aspirinNeuroinflammation – inflammation of the brain and spinal cord – is a major driver in a broad spectrum of neurological disorders, from acute syndromes like stroke and head injury to chronic neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of drug therapy against inflammatory conditions from arthritis to headaches to back pain. And there are indications that daily use of some NSAIDs (for instance aspirin) may fend off conditions of neuroinflammatory origin such as Alzheimer’s and Parkinson’s.

There’s also good evidence that much of neuroinflammation’s sting can be traced to barbs called microglia - a collective term denoting the brain’s very own set of immune cells. As first-rate scientists including Ben Barres, MD, PhD, and others have written, malfunctioning microglia may underlie much of what goes wrong in the arc of neurodeneration.

A new study by Stanford neuroscientist Kati Andreasson, MD, suggests that putting the chill on neuroinflammation by shutting down a particular protein on the surface of microglial cells may be beneficial.

In a 2011 release describing earlier work along these lines by Andreasson, I wrote:

NSAIDs block both COX-2 and COX-1, two very similar versions of cyclo-oxygenase, an enzyme that catalyzes a key chemical reaction in the production of five related hormone-like messenger molecules called prostaglandins… Prostaglandins travel from one cell to another, landing on… dedicated receptor molecules sitting on cells’ surfaces and stimulating various activities inside those cells. Each type of prostaglandin can trigger distinct effects. One prostaglandin in particular, PGE2, is known to be associated with pain and inflammation. PGE2 has four separate counterpart receptors, designated EP1 through EP4, each of which sets in motion a different set of activities inside cells on binding to PGE2.

In the new study, which appears in the Journal of Neuroscience, Andreasson and her colleagues (including fellow Stanford neuroscientist Marion Buckwalter, MD, PhD,) specifically blocked PGE2’s function in mice’s microglia. Doing this reduced brain inflammation in the presence of toxins that are known to be highly neuroinflammatory – including one called MPTP, a substance that has caused Parkinson’s disease among young drug users. Importantly, nerve cells located in the substantia nigra, a tract whose demise is a central feature of Parkinson’s disease, suffered much less damage in the presence of MPTP among mice whose microglia were missing PGE2.

“NSAIDs have a number of adverse effects, because blocking the COX enzymes blocks not only toxic prostaglandin actions but beneficial ones as well,” Andreasson told me. “If we can put our finger on prostaglandins’ toxic downstream effects, such as the microglial effect examined in this paper, we should be able to generate safer, stronger therapies in neurological disease, and other diseases as well.”

Previously: Untangling the inflammation/Alzheimer’s connection, When brain’s trash collectors fall down on the job, neurodegeneration risk picks up, Malfunctioning microglia – brain cells that aren’t nerve cells – may contribute big time to ALS and other neurological disorders and Neuroinflammation, microglia and brain health in the balance
Photo by wilbanks

Cardiovascular Medicine, Pregnancy, Research, Sleep, Stroke, Women's Health

Study shows women with gestational diabetes at increased risk for obstructive sleep apnea

3446166224_b87396dd60Come morning, an extra hour of sleep can seem to make the sun rise (“sprinkle it with dew…”). Likewise, squandering an hour awake in the middle of the night is a major bummer. My heart went out to moms-to-be, an oft-sleep-deprived demographic, when I read about a recent study finding that women with gestational diabetes – between four and eight percent of pregnant women in the U.S. – were seven times more likely to experience obstructive sleep apnea than pregnant women without gestational diabetes. Intermittently pausing the breath, typically in intervals of 20 to 40 seconds, obstructive sleep apnea not only interrupts sleep but also can raise the risk for stroke and hypertension if left untreated.

Researchers of the study, which was accepted for publication in The Endocrine Society‘s Journal of Clinical Endocrinology & Metabolism, monitored sleep disruptions, including sleep apnea, in 45 women: 15 who were pregnant and had gestational diabetes, 15 who were pregnant and did not have gestational diabetes, and 15 who were not pregnant and did not have diabetes.

From a release:

“It is common for pregnant women to experience sleep disruptions, but the risk of developing obstructive sleep apnea increases substantially in women who have gestational diabetes,” said Sirimon Reutrakul, MD, who conducted the research at Rush University Medical Center in Chicago. “Nearly 75 percent of the participants in our study who had gestational diabetes also suffered from obstructive sleep apnea.”

The study found a strong association between obstructive sleep apnea and gestational diabetes in this group of mostly overweight or obese women. Pregnant women who did not have gestational diabetes were able to get an additional hour of sleep and had less fragmented sleep than women who had gestational diabetes.

Previously: Why untreated sleep apnea may cause more harm to your health than feeling fatiguedHow effective are surgical options for sleep apnea?A reminder that prenatal care is key to a healthy pregnancy and Study: Exercise may not stave off gestational diabetes
Photo by quinn.anya

Aging, Imaging, Neuroscience, Research, Stroke

Researchers combine brain-imaging tool and stroke test to detect early signs of dementia

Researchers combine brain-imaging tool and stroke test to detect early signs of dementia

Previous research has shown that elderly patients with an increased risk of stroke have an accelerated rate of cognitive decline. Now researchers at University of California, Los Angeles have combined a brain-imaging tool and stroke risk assessment to detect signs of cognitive decline in people without current symptoms of dementia.

In the study, a group of healthy and mildly cognitively impaired individuals with an average age of 63 completed neuropsychological testing and physical assessments to determine their stroke risk using the Framingham Stroke Risk Score. Additionally, researchers injected participants with a chemical marker called FDDNP and used positron emission tomography (PET) to image their brains. According to a university release:

The study found that greater stroke risk was significantly related to lower performance in several cognitive areas, including language, attention, information-processing speed, memory, visual-spatial functioning (e.g., ability to read a map), problem-solving and verbal reasoning.

The researchers also observed that FDDNP binding levels in the brain correlated with participants’ cognitive performance. For example, volunteers who had greater difficulties with problem-solving and language displayed higher levels of the FDDNP marker in areas of their brain that control those cognitive activities.

“Our findings demonstrate that the effects of elevated vascular risk, along with evidence of plaques and tangles, is apparent early on, even before vascular damage has occurred or a diagnosis of dementia has been confirmed,” said the study’s senior author, Dr. Gary Small… Researchers found that several individual factors in the stroke assessment stood out as predictors of decline in cognitive function, including age, systolic blood pressure and use of blood pressure–related medications.

The work appears in the April issue of the Journal of Alzheimer’s Disease.

Previously: How new imaging technologies may help advance early diagnosis of Alzheimer’s, Alanna Shaikh talks about preparing for Alzheimer’s, Common genetic Alzheimer’s risk factor disrupts healthy older women’s brain function, but not men’s and Alzheimer’s disease: Why research is so critical

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