fbpx

News

ISRIB molecule—image by the Adam Frost lab at UCSF

Drug Reverses Age-Related Mental Decline Within Days, Suggesting Lost Cognitive Ability is Not Permanent

By Good News Network, December 27, 2020

 
Just a few doses of an experimental drug that reboots protein production in cells can reverse age-related declines in memory and mental flexibility in mice, according to a new study by UC San Francisco scientists.

The drug, called ISRIB, has already been shown in laboratory studies to restore memory function months after traumatic brain injury (TBI), reverse cognitive impairments in Down Syndrome, prevent noise-related hearing loss, fight certain types of prostate cancer, and even enhance cognition in healthy animals.

In the new study, published Dec. 1 in the open-access journal eLife, researchers showed rapid restoration of youthful cognitive abilities in aged mice, accompanied by a rejuvenation of brain and immune cells that could help explain improvements in brain function—and with no side effects observed.

“ISRIB’s extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological “blockage” rather than more permanent degradation,” said Susanna Rosi, PhD, Lewis and Ruth Cozen Chair II and professor in the departments of Neurological Surgery and of Physical Therapy and Rehabilitation Science.

“The data suggest that the aged brain has not permanently lost essential cognitive capacities, as was commonly assumed, but rather that these cognitive resources are still there but have been somehow blocked, trapped by a vicious cycle of cellular stress,” added Peter Walter, PhD, a professor in the UCSF Department of Biochemistry and Biophysics and a Howard Hughes Medical Institute investigator. “Our work with ISRIB demonstrates a way to break that cycle and restore cognitive abilities that had become walled off over time.”

Rebooting cellular protein production holds key to aging

Walter has won numerous scientific awards, including the Breakthrough, Lasker and Shaw prizes, for his decades-long studies of cellular stress responses. ISRIB, discovered in 2013 in Walter’s lab, works by rebooting cells’ protein production machinery after it gets throttled by one of these stress responses—a cellular quality control mechanism called the integrated stress response (ISR; ISRIB stands for ISR InhiBitor).

The ISR normally detects problems with protein production in a cell—a potential sign of viral infection or cancer-promoting gene mutations—and responds by putting the brakes on cell’s protein-synthesis machinery. This safety mechanism is critical for weeding out misbehaving cells, but if stuck in the ‘on’ position in a tissue like the brain, it can lead to serious problems, as cells lose the ability to perform their normal activities, according to Walter and colleagues.

In particular, their recent animal studies have implicated chronic ISR activation in the persistent cognitive and behavioral deficits seen in patients after TBI, by showing that, in mice, brief ISRIB treatment can reboot the ISR and restore normal brain function almost overnight.

The cognitive deficits in TBI patients are often likened to premature aging, which led Rosi and Walter to wonder if the ISR could also underlie purely age-related cognitive decline. Aging is well known to compromise cellular protein production across the body, as life’s many insults pile up and stressors like chronic inflammation wear away at cells, potentially leading to widespread activation of the ISR.

“We’ve seen how ISRIB restores cognition in animals with traumatic brain injury, which in many ways is like a sped-up version of age-related cognitive decline,” said Rosi, who is director of neurocognitive research in the UCSF Brain and Spinal Injury Center and a member of the UCSF Weill Institute for Neurosciences. “It may seem like a crazy idea, but asking whether the drug could reverse symptoms of aging itself was just a logical next step.”

Signature effects of aging disappeared literally overnight

In the new study, researchers led by Rosi lab postdoc Karen Krukowski, PhD, trained aged animals to escape from a watery maze by finding a hidden platform, a task that is typically hard for older animals to learn. But animals who received small daily doses of ISRIB during the three-day training process were able to accomplish the task as well as youthful mice—and much better than animals of the same age who didn’t receive the drug.

The researchers then tested how long this cognitive rejuvenation lasted and whether it could generalize to other cognitive skills. Several weeks after the initial ISRIB treatment, they trained the same mice to find their way out of a maze whose exit changed daily—a test of mental flexibility for aged mice who, like humans, tend to get increasingly stuck in their ways. The mice who had received brief ISRIB treatment three weeks before still performed at youthful levels, while untreated mice continued to struggle.

To understand how ISRIB might be improving brain function, the researchers studied the activity and anatomy of cells in the hippocampus, a brain region with a key role in learning and memory, just one day after giving animals a single dose of ISRIB. They found that common signatures of neuronal aging disappeared literally overnight: neurons’ electrical activity became more sprightly and responsive to stimulation, and cells showed more robust connectivity with cells around them while also showing an ability to form stable connections with one another usually only seen in younger mice.

The researchers are continuing to study exactly how the ISR disrupts cognition in aging and other conditions and to understand how long ISRIB’s cognitive benefits may last. Among other puzzles raised by the new findings is the discovery that ISRIB also alters the function of the immune system’s T cells, which also are prone to age-related dysfunction. The findings suggest another path by which the drug could be improving cognition in aged animals, and could have implications for diseases from Alzheimer’s to diabetes that have been linked to heightened inflammation caused by an aging immune system.

“This was very exciting to me because we know that aging has a profound and persistent effect on T cells and that these changes can affect brain function in the hippocampus,” said Rosi. “At the moment, this is just an interesting observation, but it gives us a very exciting set of biological puzzles to solve.”

Success shows the ‘serendipity’ of basic research

Rosi and Walter were introduced by neuroscientist Regis Kelly, PhD, executive director of the University of California’s QB3 biotech innovation hub, following Walter’s 2013 study showing that the drug seemed to instantly enhance cognitive abilities in healthy mice. To Rosi, the results from that study implied some walled-off cognitive potential in the brain that the molecule was somehow unlocking, and she wondered if this extra cognitive boost might benefit patients with neurological damage from traumatic brain injury.

The labs joined forces to study the question in mice, and were astounded by what they found. ISRIB didn’t just make up for some of the cognitive deficits in mice with traumatic brain injury—it erased them. “This had never been seen before,” Rosi said. “The mantra in the field was that brain damage is permanent—irreversible. How could a single treatment with a small molecule make them disappear overnight?”

Further studies demonstrated that neurons throughout the brains of animals with traumatic brain injury are thoroughly jammed up by the ISR. Using ISRIB to release those brakes lets brain cells immediately get back to their normal business. More recently, studies in animals with very mild repetitive brain injury—akin to pro athletes who experience many mild concussions over many years—showed that ISRIB could reverse increased risk-taking behavior associated with damage to self-control circuits in the frontal cortex.

“It’s not often that you find a drug candidate that shows so much potential and promise,” Walter says, calling it “just amazing”.

No side effects

One might think that interfering with the ISR, a critical cellular safety mechanism, would be sure to have serious side effects, but so far in all their studies, the researchers have observed none. This is likely due to two factors. First, it takes just a few doses of ISRIB to reset unhealthy, chronic ISR activation back to a healthier state. Second, ISRIB has virtually no effect when applied to cells actively employing the ISR in its most powerful form—against an aggressive viral infection, for example.

ISRIB has been licensed by Calico, a South San Francisco, Calif. company exploring the biology of aging, and the idea of targeting the ISR to treat disease has been picked up by many other pharmaceutical companies, Walter says.

“It almost seems too good to be true, but with ISRIB we seem to have hit a sweet spot for manipulating the ISR with an ideal therapeutic window,” Walter said.

Get more links to background studies from original article from UCSF News.
 

CLICK HERE to read the original article
 

With better devices, science can get closer to a more complete picture of how neurons interact for cognitive functionality. (Photo/iStock)

Are we getting closer to a complete brain mapping? New devices explore more regions safely

By Breanne Grady, April 13, 2018, viterbischool.usc.edu

Researchers have developed thin, flexible polymer-based materials that record activity in more subregions of the brain with safer, more specific placement.

Science has yet to unravel a complete understanding of the brain and all its intricate workings. It’s not for lack of effort.

Over many decades, multiple research studies have sought to understand the dizzying “talk,” or interconnectivity, between thousands of microscopic entities in the brain, in particular neurons. The goal: to one day arrive at a complete brain “mapping” — a feat that could unlock tremendous therapeutic potential.

Researchers at the USC Viterbi School of Engineering have developed thin, flexible polymer-based materials for use in microelectrode arrays that record activity more deeply in the brain and with more specific placement than ever before. What’s more is that each microelectrode array is made up of eight “tines,” each with eight microelectrodes which can record from a total 64 subregions of the brain at once.

Same Quality, More Safety

In addition, the polymer-based material, called Parylene C, is less invasive and damaging to surrounding cells and tissue than previous devices comprised of silicon or microwires. However, the long and thin probes can easily buckle upon insertion, making it necessary to add a dissolvable brace made up of polyethylene glycol (PEG) that prevents it from bending.

Professor Ellis Meng of the USC Viterbi Department of Biomedical Engineering said that the performance of the new polymer-based material is on par with microwires in terms of recording fidelity and sensitivity. “The information that we can get out is equivalent, but the damage is much less,” Meng said. “Polymers are gentler on the brain, and because of that, these devices get recordings of neuronal communication over long periods of time.”

As with any prosthetic implant, caution must be exercised in terms of the body’s natural immune response to a foreign element. In addition to inflammation, previous microelectrode brain implants made of silicon or microwires have caused neuronal death and glial scarring, which is damage to connective tissue in the nervous system. However, Parylene C is biocompatible and can be microfabricated in extremely thin form to mold well to specific subregions of the brain, allowing for exploration with minimal damage.

Listening In

So far, these arrays have been used to record synaptic responses of individual neurons within the hippocampus, a part of the brain responsible for memory formation. If injured, the hippocampus may be compromised, resulting in a patient’s inability to form new memories. Meng, a faculty member of the Michelson Center for Convergent Bioscience, said that the polymer-based material can conform to a specific location in the hippocampus and “listen in on a conversation” between neurons. Because there are many such “eavesdroppers” (the microelectrodes), much more information about their interconnectivity can be gleaned.

“I can pick where I want my electrodes to be, so I can match up to the anatomy of the brain,” Meng, the Dwight C. and Hildagarde E. Baum Chair, said. “Along the length of a tine, I can put a group of electrodes here and a group of electrodes there, so if we plant to a certain depth, it’s going to be near the neurons I want to record from.”

Up Next

Future research will determine the recording lifetime of polymer-based arrays and their long-term “signal-to-noise” (SNR) stability. Also, the team plans to create devices with even higher density, including a double-sided microelectrode array with 64 electrodes per tine instead of eight — making for a total of around 4,000 electrodes placed in the brain at once.

In addition to Meng, Professor Ted Berger, the David Packard Chair in Engineering, and Research Professor Dong Song (both of the USC Viterbi School of Engineering) were co-authors along with Ph.D. students Huijing Xu and Ahuva Weltman Hirschberg and post-doctoral scholar Kee Scholten. Funding was provided be the National Science Foundation (NSF) and the National Institutes of Health (NIH). The study titled “Acute in vivo testing of a conformal polymer microelectrode array for multi-region hippocampal recordings” now published in the Journal of Neural Engineering.

About the Michelson Center

The USC Michelson Center for Convergent Bioscience brings together a diverse network of premier scientists and engineers under one roof, thanks to a generous $50 million gift from orthopedic spinal surgeon, inventor and philanthropist Gary K. Michelson, and his wife, Alya Michelson. At the Michelson Center, scientists and engineers from the USC Dornsife College of Letters, Arts and Sciences, USC Viterbi School of Engineering and Keck School of Medicine of USC are working to solve some of the greatest intractable problems of the 21st century in biomedical science, including a fundamentally new understanding of the cell and new approaches for cancer, neurological and cardiovascular disease.

Read the original article
 

The Intrepid Spirit traumatic brain injury treatment center is slated to open April 2 at Camp Pendleton. (Courtesy Naval Hospital Camp Pendleton) (Photo/iStock)

Brain injury center to open at Marine base

By Linda McIntosh, March 27, 2018, sandiegouniontribune.com

A brain injury treatment center for military personnel will open its doors April 2 near the Naval Hospital Camp Pendleton.

The $11.5 million Intrepid Spirit center is the seventh of nine such facilities at military bases across the country. It is funded by the New York-based nonprofit Intrepid Fallen Heroes Fund founded in 2000 by Zachary Fisher, who also started the Fisher House Foundation for military families.

The center will operate as a part of Naval Hospital Camp Pendleton to treat active-duty military patients who suffer from the physical and psychological effects of brain injury. The center will also provide education and other resources on brain injury for veterans and the wider community.

The center will expand the hospital’s existing program at the Concussion Care Clinic, which has served more than 2,000 patients since 2014. An estimated 550-600 new patients are expected to be referred to the center each year.

“The facility will offer interdisciplinary, state-of-the-art evaluation of service members using clinical, laboratory and imaging resources to guide treatment,” said Cmdr. Paul Sargent, medical director of the Intrepid Spirit center, Naval Hospital Camp Pendleton.

The center’s specialty rehabilitation and therapy programs will focus on providing service members strategies to improve recovery from physical, emotional and spiritual injuries.

“We know that being able to be close to home, surrounded by loved ones, is a crucial part of the recovery process, so we are opening centers on the West Coast this spring at Camp Pendleton and also at Joint Base Lewis-McChord in Washington in order that service members who need treatment do not have to uproot themselves and their families to get it,” said David Winters, president of the Intrepid Fallen Heroes Fund.

Two teams of clinicians will serve the clinic. Their specialties range from neurology, physical medicine and rehabilitation, psychiatry, trauma psychology, neuropsychology and pain psychology to physical and occupational therapy, creative arts therapy and neuro-optometry.

“Our approach is a broadly collaborative center for preventing, treating and researching head trauma and injury to the brain,” Sargent said.

The Intrepid Spirit center includes research, education and clinical staff from the Defense and Veterans Brain Injury Center, which is part of the Department of Defense’s Health Agency.

“Teaching Marines, sailors and their commands about the risks of head injury, how to mitigate concussions and how to understand Traumatic Brain Injury signs and symptoms, along with how to improve readiness is a major goal of our TBI training,” said Regional Education Coordinator Clint Pearman, a certified brain injury specialist with the Defense and Veterans Brain Injury Center.

Pearman provides outreach, education, training and resources for medical personnel, military commands, service members, veterans and family members and civilian community groups from the Camp Pendleton area up to northern California.

The center’s design is based on the original National Intrepid Center of Excellence, which opened in 2010 at the Walter Reed National Military Medical Center in Bethesda, Md., operated by the Department of Defense.

“There are hundreds of thousands of U.S. service members who continue to suffer from traumatic brian injury and other psychological health conditions,” Winters said. “The Intrepid Fallen Heroes Fund has tried to help these brave men and women get the best care available, so we made it our mission to build nine Intrepid Spirit centers that provide comprehensive, state-of-the-art treatment.”

The clinic’s ground breaking was last May and a grand opening ceremony will be held at 11 a.m. April 4 at the Intrepid Spirit Center.

For information about base access, visit pendleton.marines.mil/About/Base-Information/Base-Access.

Read the original article
 

 

The radial-arm water maze is a common test to assess working memory in rodents.

Memory-enhancing drug reverses effects of traumatic brain injury in mice

By Ryan Cross, Jul. 10, 2017, sciencemag.org

Whether caused by a car accident that slams your head into the dashboard or repeated blows to your cranium from high-contact sports, traumatic brain injury can be permanent. There are no drugs to reverse the cognitive decline and memory loss, and any surgical interventions must be carried out within hours to be effective, according to the current medical wisdom. But a compound previously used to enhance memory in mice may offer hope: Rodents who took it up to a month after a concussion had memory capabilities similar to those that had never been injured.

The study “offers a glimmer of hope for our traumatic brain injury patients,” says Cesario Borlongan, a neuroscientist who studies brain aging and repair at the University of South Florida in Tampa. Borlongan, who reviewed the new paper, notes that its findings are especially important in the clinic, where most rehabilitation focuses on improving motor—not cognitive—function.

Traumatic brain injuries, which cause cell death and inflammation in the brain, affect 2 million Americans each year. But the condition is difficult to study, in part because every fall, concussion, or blow to the head is different. Some result in bleeding and swelling, which must be treated immediately by drilling into the skull to relieve pressure. But under the microscope, even less severe cases appear to trigger an “integrated stress response,” which throws protein synthesis in neurons out of whack and may make long-term memory formation difficult.

In 2013, the lab of Peter Walter, a biochemist at the University of California, San Francisco (UCSF), discovered a compound—called ISRIB—that blocked the stress response in human cells in a dish. Surprisingly, when tested in healthy mice, ISRIB boosted their memory. Wondering whether the drug could also reverse memory impairment, Walter teamed up with UCSF neuroscientist Susanna Rosi to study mouse models of traumatic brain injury. First, they showed that the stress response remains active in the hippocampus, a brain region important for learning and memory, for at least 28 days in injured mice. And they wondered whether administering ISRIB would help.

Rosi and her team first used mechanical pistons to hit anesthetized mice in precise parts of their surgically exposed brains, resulting in contusive injuries, focused blows that can also result from car accidents or being hit with a heavy object. After 4 weeks of rest, Rosi trained the mice to swim through a water maze, where they used cues to remember the location of a hidden resting platform. Healthy mice got better with practice, but the injured ones didn’t improve. However, when the injured mice were given ISRIB 3 days in a row, they were able to solve the maze just as quickly as healthy mice up to a week later, the researchers report today in the Proceedings of the National Academy of Sciences.

“We kept replicating experiments, thinking maybe something went wrong,” Rosi says. So the team decided to study ISRIB in a second model of traumatic brain injury known as a closed head injury, which resembles a concussion from a fall. They again used a mechanical piston, but this time landed a broad blow to the back of the skull. Two weeks later, the mice were trained on a tougher maze, full of bright lights and loud noise. They had to scurry around a tabletop with 40 holes, looking for the one with an escape hatch. Again, while the uninjured mice improved at the task, the concussed mice never got the hang of it. But after four daily doses of ISRIB, the concussed mice performed as well as their healthy counterparts. “This is the most exciting piece of work I’ve ever done, no doubt,” Rosi says.

“Paradigm shift is not too strong a term to use,” says Ramon Diaz-Arrastia, neurologist and director of clinical traumatic brain injury research at the University of Pennsylvania. “This … shows for the first time that a therapy in the chronic period of traumatic brain injury can have pretty potent effects.” Walter agrees. “Normally you would give up on these mice and say nothing can be done here,” he says. “But ISRIB just magically brings the cognitive ability back.”

Still, Borlongan cautions that studies in animals often don’t pan out when tested in humans. He says that this drug has a leg up, though, because it was tested in two models and also readily crosses the blood-brain barrier, which prevents many drugs that look good on paper from entering the brain and having an effect.

If the therapy translates to humans, it could be a boon for soldiers returning from war, who sometimes wait weeks between leaving the battlefield and arriving home for treatment. Brian Head, a neurobiologist at the VA San Diego Healthcare System in California notes that traumatic brain injury is still hard to diagnose, especially with veterans that show up to the clinic long after the injury. “But right now nothing else is working, and giving a compound [that works] a month later is really impressive.”

In 2015, ISRIB was licensed to the secretive Google spinout company Calico, which studies the biology of aging and life span. Walter says his lab has a research agreement with Calico to pursue “basic mechanistic work” on ISRIB, but that the new study was not funded by Calico. Google declined to comment on the new research.

Although the protein target of ISRIB is known, the exact manner in which the drug restores memory is hazy. The team hypothesizes that ISRIB may work by allowing normal protein synthesis—essential for making new neuronal connections and thus forming new memories—to resume, which would otherwise be blunted by the integrated stress response. “Even if this drug doesn’t materialize, other ways of manipulating the integrated stress response may lead to an effective treatment in the future,” Walter says.

Read the original article
 

 
The Cohen family partners with USC to serve families in Los Angeles.
 
by Lynn Lipinski, tfm.USC.edu (Autumn 2016) — PEACE AFTER WAR can be elusive for combat veterans who fight painful memories long after they’ve left the battlefield. Of the more than 2.6 million men and women who have served in the U.S. military since 9/11, about 20 percent experience some form of post-traumatic stress or brain injury—but nearly half forego treatment, according to the Cohen Veterans Network.

The Steven A. Cohen Military Family Clinic at USC, made possible by a $15.7 million gift from Steven Cohen and the Cohen Veterans Network, offers veterans and their family members free outpatient mental health services and case management. Recently opened in downtown Los Angeles, the Cohen Military Family Clinic at USC is part of a national network of clinics serving veterans and is a collaboration between the USC School of Social Work and the Keck School of Medicine of USC.

Providers will also be stationed at locations throughout the county in areas that otherwise lack these types of services. The clinic will also serve veterans who are ineligible for Veterans’ Admnistration benefits, such as those who served in the National Guard or the Reserves.

“The wounds of war are serious. It is not easy to serve your country in combat overseas and then come back into society seamlessly, especially if you are suffering,” says Cohen, chairman and CEO of Point72 Asset Management. “Veterans have paid an incredible price. It’s important that this country pays back that debt.”

The Cohen Veterans Network plans to create a system of about two dozen centers across the country by 2020 as part of a $275 million initiative to improve access to behavioral health care for recent veterans. Cohen’s support of services for veterans began in part because of a personal connection: His son, Robert, deployed to Afghanistan with the Marines and is currently in the Reserves.

USC’s strong programs for veterans made it a natural fit to host the clinic. The USC School of Social Work is home to the Center for Innovation and Research on Veterans and Military Families, where researchers conducted the first comprehensive study of veterans in L.A. County. Their findings are already helping to create effective services for veterans. The school has also earned national recognition for its pioneering master’s degree in military social work—the only program of its kind offered by a civilian research university.

Read the original article
 

By John Prybys, LAS VEGAS REVIEW-JOURNAL (August 22, 2016) — Randy Dexter and Captain are more than just dog owner and dog. That’s obvious from the way Captain looks for Dexter whenever the Army veteran leaves the room, and the way the Lab mix’s demeanor slips instantly from playful to dead serious once he’s wearing the jacket that denotes his status as a service animal.

Dexter is a retired U.S. Army staff sergeant who did two tours of duty in Iraq. He was diagnosed with both post-traumatic stress disorder and a mild traumatic brain injury, and the story of Dexter and Captain is featured in a new awareness campaign urging veterans and military service people to seek help for traumatic brain injury if they need it.

The campaign, “A Head for the Future,” is sponsored by the Defense and Veterans Brain Injury Center. In his video, Dexter shares the struggles he has experienced coping with his injuries and the reluctance he felt at first to seek help for it.

But, he says, “I was lucky, because when I was in the Army and had my head injury, I was kind of forced to get help.”

Dexter, 34, is a graduate of Green Valley High School who served in the Army for 11 years and had two tours of duty in Iraq. In 2005, Dexter, a combat medic, and his squad were hit by an IED, prompting a long, and continuing, struggle with post-traumatic stress disorder.

Then, after returning home and while still being treated for PTSD and training soldiers bound for Iraq and Afghanistan, Dexter suffered a brain injury during a recreational football game. He’s not sure, even now, what happened. All he knows is that he lost the memory of about 24 hours’ time and, even, of going to the game at all.

X-rays and imaging studies revealed no skull fractures or apparent injuries. But, afterward, Dexter experienced a worsening of already existing problems with his memory, concentration and equilibrium, and began to suffer migraines and severe, debilitating headaches that eventually compounded his PTSD and caused severe depression.

Dr. Scott Livingston, director of education for the Defense and Veterans Brain Injury Center in Silver Springs, Maryland, says symptoms of PTSD and brain injury often can overlap, making diagnosis a challenge. And when a brain injury does occur, he says, it often presents with no obvious symptoms that can be detected by X-ray or imaging scans.

In such cases, the problem likely is “more of a microscopic type of injury within the brain,” Livingston says.

Most civilians probably assume that brain injuries among service people are caused mostly by blasts and blunt-force trauma to the head. Yet, Livingston says, most are caused by motor vehicle collisions, training-related accidents, falls and sports and recreational activities.

Whatever the cause, military personnel are reluctant to report an injury or seek care for it. The current campaign is designed to raise awareness of brain injuries among service people, promote ways to prevent it when possible, and encourage men and women to report it and get it checked out, Livingston says.

“It’s well-known in scientific literature that the earlier someone reports a mild traumatic brain injury and goes to seek help, the better the chances are for better and more complete recovery,” he says.

During his treatment, Dexter participated in a program that paired injured veterans with service dogs. His experience with a dog named Ricochet was so good that he later welcomed the chance to be paired with Captain.

Dexter and Captain are a great team. Dexter says the dog can detect impending anxiety attacks even before he does, and that the dog can serve as a physical shield and protector in such public places as big-box retail stores, which can be particularly unnerving places for those with PTSD.

The true test of Captain’s effectiveness is that the dog has allowed Dexter to significantly reduce the medications he has to take. Today, it would be difficult for someone who doesn’t know the back story to detect Dexter’s struggles with traumatic brain injury, and it was his own previous interest in speaking out publicly about his conditions that led to his participation in the new awareness campaign.

Dexter now attends UNLV, where he’s majoring in communication studies and Spanish. He has been active on the debate teams, will be a peer adviser for other veterans, and hopes to kick off a music show on the university’s HD/internet radio station.

Dexter hopes his video and his story will help to persuade other veterans and active service people to seek out help for PTSD and brain injury. That can be difficult, he notes, because the standard soldier’s stance is that, whatever is happening, “you just deal with it, and that’s true across the whole military culture.”

Read the original article
 

By Alyssa Navarro, Tech Times (August 23, 2016) — Federal health regulators in the United States approved on Monday the use of two new computer softwares as cognitive screening tests for traumatic head injury patients.

Known as ImPACT or the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), the new testing device, as well as a similar test designed for children, can be used by doctors to evaluate signs and symptoms of head injuries that could indicate concussion.

ImPACT is designed for patients aged 12 to 59 years old, while ImPACT Pediatric is intended for children aged 5 to 11 years old, officials said. Licensed health care professionals are the only ones allowed to perform the analysis and interpret the results.

The software can be accessed easily because it runs on both desktop computers and laptops, according to the U.S. Food and Drug Administration (FDA). Both tests the first ever devices permitted by the FDA to assess cognitive function after experiencing a possible concussion. They are designed to be part of medical evaluations in hospitals.

Although ImPACT and ImPACT Pediatric will definitely be useful for doctors, both tests are not meant to diagnose concussions or determine treatments that are appropriate for such cases, the FDA said.

Instead, both devices are only designed to test cognitive skills such as reaction time, memory and word recognition. All of these can be impacted by head injuries. Afterwards, the results are compared to a patient’s pre-injury baseline scores or an age-matched control database, the FDA said.

Dr. Carlos Peña, director of the neurological and physical medicine division at the Center for Devices and Radiological Health, acknowledges that the two testing devices can provide useful information that can aid doctors in the evaluation of people who are experiencing potential signs of concussion.

However, Peña says that clinicians should not completely depend on the tests alone to rule out concussion or to decide whether a player with a head injury should return to a game.

Statistics from the Centers for Disease Control and Prevention (CDC) reveal that traumatic brain injuries are responsible for more than 2 million visits to the emergency room in the country annually. Traumatic brain injuries also account for more than 50,000 deaths in America every year.

Cases of head injury among kids have been increasing. In May, a CDC report showed that from January 2001 to December 2013, approximately 214,883 children aged 14 years old and below were brought to emergency departments due to head injuries.

Read the original article
 

When a person has a stroke, blood flow to the brain is interrupted, causing brain cells to die within minutes due to lack of oxygen. In some cases, this can result in paralysis, speech and language problems, vision problems, and memory loss. But in a new study, researchers have shown that stem cell therapy increases nerve cell production in mice with brain damage due to stroke.

by Marie Ellis, MedicalNewsToday.com (August 22, 2016) — The researchers – led by Berislav Zlokovic, M.D., Ph.D., from the University of Southern California (USC) – publish their findings in the journal Nature Medicine.

According to the Centers for Disease Control and Prevention (CDC), stroke is the fifth leading cause of death in the United States and is also a major cause of disability in adults.

The effects of a stroke depend on the location of the blockage and how much brain tissue is involved, but a stroke on one side of the brain will result in neurological effects on the opposite side of the body.

For example, a stroke on the right side of the brain could produce paralysis on the left side of the body, and vice versa.

A stroke in the brain stem can affect both sides of the body and could leave the patient in a so-called locked-in state, where the patient is unable to speak or move the body below the neck.

Given that about 800,000 people in the U.S. have a stroke each year, the researchers of this latest study wanted to investigate potential therapies.

Therapy is a combination of two methods

The researchers say their therapy is a combination of two methods. One involves surgically grafting human neural stem cells onto the damaged area, where they are able to mature into neurons and other brain cells.

The other therapy uses a compound called 3K3A-APC, which has been shown to help neural stem cells that have been grown in a petri dish grow into neurons. But the researchers say it was not clear what effect the molecule – called activated protein-C (APC) – would have on live animals.

As such, the team used mice for their experiment, and they found that a month after inducing stroke-like brain damage in the mice, those that had received both the stem cells and 3K3A-APC performed much better on motor and sensory function tests, compared with mice that received only one of the treatments or neither.

The researchers also observed that the mice given 3K3A-APC had more stem cells survive and mature into neurons.

But how did the researchers induce stroke-like brain damage in the mice? They disrupted blood flow to a specific brain area.

Then, 1 week later, which is the mouse equivalent of several months in humans, the researchers inserted the stem cells next to the dead tissue and administered either a placebo or 3K3A-APC.

“When you give these mice 3K3A-APC, it works much better than stem cells alone,” says Dr. Zlokovic. “We showed that 3K3A-APC helps the cells convert into neurons and make structural and functional connections with the host’s nervous system.”

‘No one in the stroke field has ever shown this’

The researchers also looked at the connections between the neurons that grew from the stem cells in the damaged brain region and nerve cells in the primary motor cortex.

The team found that the mice given the stem cells and 3K3A-APC had more neuronal connections – synapses – that linked those areas, compared with the mice given the placebo.

Then, when the researchers stimulated the mice’s paws with a vibration, the neurons that grew from the stem cells exhibited a stronger response in the mice that were treated.

“That means the transplanted cells are being functionally integrated into the host’s brain after treatment with 3K3A-APC. No one in the stroke field has ever shown this, so I believe this is going to be the gold standard for future studies.” ~Dr. Berislav Zlokovic

Following on from this study, the researchers want to pursue another phase II clinical trial to examine whether the treatment combination can encourage the growth of new neurons in human stroke patients to improve function.

They say that if that trial is successful, it could be possible to test the therapy’s effects on other conditions, including spinal cord injuries.

“This USC-led animal study could pave the way for a potential breakthrough in how we treat people who have experienced a stroke,” says Jim Koenig, Ph.D., program director at the National Institute of Health’s National Institute of Neurological Disorders and Stroke (NINDS), who funded the study.

“If the therapy works in humans,” he adds, “it could markedly accelerate the recovery of these patients.”

Read the original article

UCSF Researchers Advocate Prioritizing Teens for Education and Prevention

by Scott Maier (August 17, 2016) — The number of Americans diagnosed with concussions is growing, most significantly in adolescents, according to researchers at UC San Francisco. They recommend that adolescents be prioritized for ongoing work in concussion education, diagnosis, treatment and prevention.

The findings appear online August 16, 2016, in the Orthopaedic Journal of Sports Medicine.

“Our study evaluated a large cross-section of the U.S. population,” said lead author Alan Zhang, MD, UCSF Health orthopaedic surgeon. “We were surprised to see that the increase in concussion cases over the past few years mainly were from adolescent patients aged 10 to 19.”

Concussions are a form of mild traumatic brain injury resulting in transient functional and biochemical changes in the brain. They can lead to time lost from sports, work and school, as well as significant medical costs.

Though symptoms resolve in most concussion patients within weeks, some patients’ symptoms last for months, including depression, headache, dizziness and fogginess. Neuroimaging and neuropathological studies also suggest there may be chronic structural abnormalities in the brain following multiple concussions.

Recent studies have shown an increase in traumatic brain injuries diagnosed in many U.S. emergency departments. Smaller cohort studies of pediatric and high school athletes also have indicated a rise in concussions for certain sports, such as football and girls’ soccer. However, this is the first study to assess trends in concussion diagnoses across the general U.S. population in various age groups.

In this study, Zhang and his colleagues evaluated the health records of 8,828,248 members of Humana Inc., a large private payer insurance group. Patients under age 65 who were diagnosed with a concussion between 2007-2014 were categorized by year of diagnosis, age group, sex, concussion classification, and health care setting of diagnosis (emergency department or physician’s office).

Overall, 43,884 patients were diagnosed with a concussion, with 55 percent being male. The highest incidence was in the 15-19 age group at 16.5 concussions per 1,000 patients, followed by ages 10-14 at 10.5, 20-24 at 5.2 and 5-9 at 3.5.

The study found that 56 percent of concussions were diagnosed in the emergency department, 29 percent in a physician’s office, and the remainder in urgent care or inpatient settings. As such, outpatient clinicians should have the same confidence and competence to manage concussion cases as emergency physicians, Zhang said.

A 60 percent increase in concussions occurred from 2007 to 2014 (3,529 to 8,217), with the largest growth in ages 10-14 at 143 percent and 15-19 at 87 percent. Based on classification, 29 percent of concussions were associated with some loss of consciousness.

A possible explanation for the significant number of adolescent concussions is increased participation in sports, said Zhang, MD, who is also assistant professor of orthopaedic surgery at UCSF. It also may be reflective of an improved awareness for the injury by patients, parents, coaches, sports medical staff and treating physicians.

For example, the U.S. Centers for Disease Control and Prevention “HEADS UP” initiative has caused numerous states such as California to alter guidelines for youth concussion treatment.

Many medical centers also are establishing specialty clinics to address this, which could be contributing to the increased awareness. At UCSF, the Sports Concussion Program evaluates and treats athletes who have suffered a sports-related concussion. The team includes experts from sports medicine, physical medicine and rehabilitation, neuropsychology and neurology. Their combined expertise allows for evaluation, diagnosis and management of athletes with sports concussions, helping them safely recover and return to sports.

Other UCSF orthopaedic surgery contributors to the Orthopaedic Journal of Sports Medicine study were senior author Carlin Senter, MD, associate professor; Brian Feeley, MD, associate professor; Caitlin Rugg, MD, resident; and David Sing, clinical research associate.

UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospital San Francisco, and other partner and affiliated hospitals and healthcare providers throughout the Bay Area.

Read the original article
 

Serving the Brain Injury Community for 30+ years