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SPEAK OUT! NewsBit . . . . . . Repair of Neural Circuits in Stroke-damaged Mouse Brains

SPEAK OUT! NewsBit

Repair of Neural Circuits in Stroke-damaged Mouse Brains

presented by

Donna O’Donnell Figurski

 

 

newsboy-thBasic research on the repair of damaged mouse brains has again produced a potential breakthrough for human therapy. The research may accelerate our ability to repair damaged human brains. A trial study for using this therapy in humans is now being designed.

I’ve already written about the extraordinary promise of cell therapy in eliminating or greatly reducing the effects of brain damage. Much of this promise has to do with the discovery of stem cells, which have the stunning ability to develop into virtually any kind of cell. (The previous NewsBit, however, showed that scientists found a way to cause a common cell type to develop into functional neurons directly without going through a stem-cell stage.) In a study earlier this year, scientists showed that stem cells surgically implanted into damaged human brains reduced the severity of symptoms. But in that study, the scientists were surprised to find that the added stem cells themselves did not become new neurons and form new circuits, but they somehow revved up the brain’s natural ability to heal itself.animal-cell-hi

Now scientists at the University of Southern California (USC) with help from scientists at the National Institutes of Health (NIH) have found a way to activate the implanted stem cells so they develop into neurons and become part of new neural circuits. The direct involvement of the added stem cells resulted in enhanced repair and a much greater loss of symptoms. One NIH scientist said, “If the therapy works in humans, it could markedly accelerate the recovery of these patients.”

CellScientists had previously shown that an FDA (Food and Drug Administration)-approved reagent, the engineered protein 3K3A-APC, caused stem cells in culture to become neurons. The USC scientists wanted to see if 3K3A-APC would help the recovery of a brain-injured animal. The model used for brain damage was mice that were induced to have a stroke. The scientists implanted human stem cells and then treated the mice with 3K3A-APC or a placebo (mock-3K3A-APC). Mice that were treated with stem cells + 3K3A-APC did markedly better (some were almost normal) in tests of sensory perception and motor skills than did mice that were treated with stem cells + the placebo. Unlike the earlier study in which the added stem cells did not become neurons, these stem cells did become neurons if the mouse had been treated with 3K3A-APC.

ScientistThe human stem cells not only became neurons, but they also formed normal connections with mouse neurons. Because the implanted cells were human, the scientists were able to use a human-specific toxin to kill only the implanted cells (the mouse cells were resistant to the toxin). When scientists killed the new neurons, the mice lost the signs of recovery. The scientists concluded that 3K3A-APC caused the cells to develop into neurons that then formed functional neural circuits, ultimately leading to recovery.Brain Cell

USC physician-scientist Berislav Zlokovic, M.D., Ph.D., who directed the research, said, “When you give these mice 3K3A-APC, it works much better than stem cells alone. We showed that 3K3A-APC helps the cells convert into neurons and make structural and functional connections with the host’s nervous system.” (Full story)

 

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SPEAK OUT! NewsBit . . . . . . Common Mouse Cell Type Converted to Neurons

SPEAK OUT! NewsBit

Common Mouse Cell Type Converted to Neurons

presented by

Donna O’Donnell Figurski

 

newsboy-thCommon Mouse Cell Type Converted to Neurons

You’ve probably heard of the promising future of cell therapy. The excitement comes from the fact that injuries might be treated by implanting fresh, healthy cells. Stem cells, which can mature to many different cell types, have been discovered in almost every organ in the body. They hold enormous potential for helping to heal injured organs. Already, scientists are devising methods to add new muscle to damaged hearts and to add insulin-producing cells to the body to cure Type I diabetes. The brain also has stem cells, and much of the natural recovery from brain injury is due to stem cells, which rebuild the damaged part of the brain. The beauty of stem cells from the brain is that they can develop into healthy neurons and replace damaged circuits. But the natural healing of the brain is often insufficient. Scientists have been looking for ways to make more stem cells and to activate them so that implanting them is practical and they can result in more healing.scientist

I want to tell you about exciting basic research on cell therapy that may make possible or speed up the development of new therapies for brain injury. Scientists at Duke University have found a way to make neurons from common mouse cells, called “fibroblasts,” without resorting to stem cells. The scientists made a modified protein and put it into fibroblasts. The modified protein found and activated the master regulator genes needed to turn on the genes for the cell to become a neuron.

In the past, a cell’s change into a neuron required that extra copies of the master regulator genes be introduced into the cell. The cell maintained its neuron-like properties only if the extra activators were present. If the extra copies were lost, the cell reverted to its original form. Scientists said that the neurons were “unstable.” Still, it was a breakthrough. To help stabilize the neurons, extra copies of genes for the master regulators were added to its chromosomes. The neurons still weren’t perfectly stable, and the presence of extra copies in the chromosomes was unnatural.

In the new method, activation of the neuron genes is natural. The neurons are “stable,” even when the modified activator protein is gone. As far as the scientists can tell, the neurons formed this way appear to be like natural neurons.

MouseOf course, these studies need to be done with human cells. But, because the mouse is similar enough to humans genetically, new neurons are likely to be made from human cells. If so, cell therapy to treat brain injury will become common in the foreseeable future. One benefit is that therapy can be personalized. It’s not practical to get your neurons from a brain biopsy, but your easy-to-get fibroblasts can be converted to neurons. Those neurons can then be tested with therapeutic drugs to see what works best with your genetic background. Also, the implanted cells would not be rejected by your body (prevention of rejection is the reason for immunosuppressive drugs today) because the neurons would be made from cells of your own body. (Full story)

 

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SPEAK OUT! NewsBit . . . . . . Inosine Helps Brain-Injured Monkeys Recover Fine Motor Control

SPEAK OUT! NewsBit

Inosine Helps Brain-Injured Monkeys Recover Fine Motor Control

presented by

Donna O’Donnell Figurski

My husband, David, is a traumatic brain injury survivor since 2005. He is physically disabled as a result of his brain injury. As a molecular biologist from Columbia University, David is always searching for ways to improve his own life after his brain injury. He recently stumbled on this exciting research project, and we wanted to share this hopeful concept with others.

 

Disclaimer:

Neither David nor I is a medical doctor, and we are not suggesting any medical solutions. We are only publishing this article for your information.

 

Newsboy th

 

Inosine is a small molecule found in cells. Research with mice and rats has shown that inosine is released by stressed or damaged neurons. Inosine can turn on the genes for axon development. Axons are the long, threadlike membrane extensions needed for neurons to send an electrochemical message to other neurons. The new axons from undamaged neurons can rewire the brain (plasticity) to allow circuits to form that compensate for circuits lost from damage.

Adding inosine to neurons in culture stimulates the formation of more axons. Would inosine stimulate an increase in plasticity by increasing axon formation and thereby help recovery from brain injury? Consistent with this idea, neuroscientists found that rats recovered from brain injury better when inosine was present.pTqKnRpgc

Now neuroscientists at Boston University report testing inosine’s effect on a primate – the rhesus monkey. The study was small (8 monkeys) because monkey experiments are expensive, but, despite the small number, the results were significant. At the beginning, all 8 monkeys could easily grasp food treats with their dominant hand. The part of the brain needed for the required motor skills in the dominant hand was then deliberately damaged in each monkey. The 8 brain-injured monkeys were divided into two groups: 4 monkeys were treated by giving them inosine, and 4 were given a placebo. The researchers didn’t know which monkeys were getting inosine and which were getting the placebo.

After 14 weeks of treatment, the monkeys were examined for their ability to grasp a food treat. Three of the four inosine-treated monkeys grasped the food with their dominant hand normally. Fine motor control in the hand seemed to be the way it was prior to the brain injury. In contrast, the placebo-treated monkeys retrieved their food by using a compensatory strategy. The placebo-treated monkeys still had a problem with fine motor control in the hand.

mouse-hiThis preliminary study has extended evidence of the inosine benefit from mice and rats to a primate. The result indicates that inosine may one day benefit human victims of brain injury. Inosine is already in clinical trials for the treatment of multiple sclerosis and Parkinson’s Disease. Inosine appears to be safe – athletes have taken inosine supplements for decades.

Strictly speaking, this experiment addressed recovery of only a specific movement. The brain injuries were highly controlled – all were nearly identical, and they were in a specific area of the frontal lobe that affects fine motor control of the hand. Inosine experiments of this type have only been done in animal models. But even with all these caveats, there is reason to be optimistic. Inosine treatment may become a common human therapy for brain injury. Clearly more research is needed before inosine is shown to be useful in the clinic. (Full story)

 

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SPEAK OUT! NewsBit: . . . . . . Wanting A “Sound Mind,” 30-Year-Old Football Player Retires

Wanting A “Sound Mind,” 30-Year-Old Football Player Retires

presented

by

Donna O’Donnell Figurski

 

husain_abdullah

Husain Abdullah – NFL Player

For seven years, Husain Abdullah played football in the National Football League (NFL), the premier professional football league in the United States. For four years, Abdullah, a safety, played with the Minnesota Vikings, and, for three years, he played with the Kansas City Chiefs. He graciously thanked both teams for allowing him to play. In the 2015 season, he had the fifth concussion of his career. While he was recovering, he thought about his many life-goals. Husain realized that he would need a “sound mind” to achieve his goals.

The research showing a link between the head trauma of football and the neurodegenerative disease CTE (chronic traumatic encephalopathy) is thought-provoking, and it has several players concerned. Even the NFL has admitted that there is a link between playing football and CTE, although the league later tried to downplay its comment. (CTE, originally known as “dementia pugilistica,” had only been seen in the brains of some boxers.

Dr. Bennet Omalu -

Dr. Bennet Omalu –

Dr. Bennet Omalu was the first to find the disease elsewhere – in a football player. Dr. Omalu renamed the disease “CTE.” Dr. Omalu’s discovery is the subject of the December 2015 movie Concussion, starring Will Smith. The real-life story is told in the PBS Frontline documentary, League of Denial: The NFL’s Concussion Crisis – available free online.)

Abdullah’s retirement follows other early retirements, most notably that of San Francisco 49er star rookie linebacker, Chris Borland, who cited the high risk of brain disease as his reason for retiring after playing only one year. Another rookie, Green Bay Packer wide receiver Adrian Coxson, retired after getting a severe concussion in practice and being told that the next hit might seriously affect his brain function or kill him.

Abdullah Husain - NFL Player

Abdullah Husain – NFL Player

It remains to be seen if Husain Abdullah’s retirement will be the last early retirement in the NFL due to football’s risk to the brain. (Full story)

 

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SPEAK OUT! NewsBit . . . . . Mental Decline Causes a Hero of Super Bowl XL to Regret Playing Professional Football

Mental Decline Causes a Hero of Super Bowl XL to

Regret Playing Professional Football

presented

by

Donna O’Donnell Figurski

 

Newsboy thAmerican football wide receiver Antwaan Randle El, who played for the Pittsburgh Steelers, is fondly remembered for doing a reverse and then throwing a touchdown pass to ice the National Football League’s Super Bowl XL, played February 2006 against the Seattle Seahawks. The final score was 21-10.

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Antwaan Randle El #82 former Pittsburgh Steeler

Randle El retired early in 2010. Now 36, he has trouble with his memory and has difficulty on stairs. He fears what the violence of football has done to his brain and regrets playing professionally. An all-around athlete, Randle El had been drafted by the Chicago Cubs, a U.S. professional team in Major League Baseball, but his life-path brought him to football. He said in an interview by the Pittsburgh Post-Gazette, “If I could go back, I wouldn’t (play football.) I would play baseball.”

 

antwaan-randle-el-0071-002

Antwaan Randle El – former Pittsburgh Steeler

Randle El wants to see his kids grow up and to know his grandkids. He is aware of recent brain research and the problems associated with playing football, so he is worried about his own neurological health. He said, “It’s a tough pill to swallow because I love the game of football. … It just comes down to it’s a physically violent game. … I wouldn’t be surprised if football isn’t around in 20, 25 years.” (Full story)

 

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SPEAK OUT! NewsBit . . . . . . Frank Gifford’s Brain Showed CTE

Frank Gifford’s Brain Showed CTE

presented

by

Donna O’Donnell Figurski

 

newsboy-thFrank Gifford died at 84 of natural causes. Because he had always been concerned with player safety and helped to found the National Football League Players Association, his family donated his brain to science for study.

Frank Gifford, a beloved running back in the 1950s and 1960s, played for the New York Giants of the National Football League.  He was inducted into the Hall of Fame, and after he retired, he became a popular and an award-winning sportscaster for Monday Night Football.  Even though Gifford showed no outward signs of neurodegenerative disease, his family said in a released Frank Gifford footballstatement that he experienced symptoms. As a running back, Gifford endured many sub-concussive hits, which many neurologists now believe contribute to neurodegenerative disease. In 1960, Gifford was knocked unconscious by a brutally hard tackle.  That concussion caused the end of his season, and he did not play the next year.

The study of Frank Gifford’s brain revealed that he had chronic traumatic encephalopathy (CTE), a brain disease found in the autopsied brains of people who played contact sports. So far, 88 of 92 brains of professional players of American football have shown CTE (1, 2). Gifford’s brain makes that statistic 89 of 93.

What makes Frank Gifford’s brain special is that Gifford died of natural causes. The other players whose brains tested positive Frank Giffordfor CTE showed symptoms of brain disease. (In fact, some of the deaths were from suicide.) The claim has been made that the group that was almost entirely positive for CTE was biased. But Dr. Ann McKee, a neuropathologist at Boston University’s CTE Center and the person who studied most of the brains, pointed out that, even in a biased sample, the number of brains testing positive for CTE is ridiculously high. Frank Gifford’s brain would not be considered part of the biased sample. (Gifford showed no outward signs of brain disease.) Yet Frank Gifford’s brain tested positive for CTE. This latest result is consistent with Dr. McKee’s worry that CTE is common among players of American football. (Full story)

 

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SPEAK OUT! NewsBit NFL Quarterback With Concussion Stays In Game

NFL Quarterback With Concussion Stays In Game

presented

by

Donna O’Donnell Figurski

 

newsboy-thThe National Football League (NFL) governs most of professional American football, and it is proud of its “concussion protocol” to protect its players. That system shamefully failed Sunday with 1:04 left in a 13-13 game between the St. Louis Rams and the Baltimore Ravens.

St. Louis quarterback, Case Keenum, had taken his team close to Baltimore territory and was trying to drive for a score. Then Keenum was

Case Keenum 1

Case Keenum Quarterback St. Louis Rams

sacked (tackled for a loss). His head hit the turf hard. Keenum couldn’t get up without assistance, and even when he did, he seemed to be staggering. He showed at least three of the signs of a possible concussion, as defined by the concussion protocol of the NFL. (A concussion was confirmed after the game. It wasn’t a surprise. Fans at the stadium and watching on TV could see Keenum was in trouble.)

Case Keenum 2

Keenum holding head after tackle

The NFL this year empowered the neurotrauma consultants, who are in the broadcast booths for all games, to stop games if necessary. Yet the St. Louis-Baltimore game continued, and Case Keenum remained in it. He fumbled after two plays. Baltimore recovered, which set up a field goal to win the game.

Case Keenum 3

Keenum struggling to return to game

This case seems to show more concern with winning than with Keenum’s health and safety. Both the NFL and the NFL Player’s Association (NFLPA) are investigating. It’s not clear if anyone – the coach, the trainer,

Concussed Brain

Concussed Brain

or the neurotrauma consultant – was at fault. But whatever happened, the system totally failed. (Full story with video)

 

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SPEAK OUT! NewsBit . . . . . . U.S. Soccer Bans Heading for Players Age 10 and Under

U.S. Soccer Bans Heading for Players Age 10 and Under

presented

by

Donna O’Donnell Figurski

newsboy-thConcussions from playing soccer rank second to football in boys’ sports, but they are first in girls’ sports and second among all sports. Of the more than 3 million youths playing soccer in the U.S., 50,000 concussions were reported among high-school soccer players in 2010, more than the number from wrestling, basketball, baseball, and softball combined.  Parents and players brought a lawsuit accusing U.S. Soccer and other U.S. youth soccer organizations of negligence. As a result, U.S. Soccer established new rules that prevent heading by players age 10 and under and prohibits heading by 11- to 13-year-olds in practice. There are also new guidelines for soccer-trophy-clipart-soccer-team-clipartsoccer-team-with-trophy-clip-art-soccer-team-with-trophy-image-efwxwwe3substitution. For example, a player who replaces another player who has to leave the game because of a suspected concussion does not count as a substation.

U.S. Soccer governs only a fraction of youth soccer teams in the U.S., so they are recommending strongly that other leagues follow suit.  Dr. Cantu, a neurologist and a concussion specialist at Boston University, said that children’s brains are crucially developing and that the ages of 10 to 14 are especially critical in brain development. He also maintains that children’s neck muscles are not strong enough to support the head, making the risk of injury even greater. Safer Soccer, an organization that seeks a ban on 131181714310586452912266140-vector-illustration-for-a-anatomy-brain-in-separate-color-mdheading for players 14 and under, applauds the new rules. (The advisory board of Safer Soccer includes Brandi Chastain, Cindy Parlow Cone, and Joy Fawcett – former players of the women’s U.S. national soccer team, which has won four Olympic gold medals since 1996.) (Full story with video)

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SPEAK OUT! NewsBit . . . . . . . . . . “Concussion” Movie Based on True Story – (trailer)

“Concussion” Movie Based on True Story – (trailer)

starring Will Smith

presented by

Donna O’Donnell Figurski

newsboy-thAmerica loves football, but the National Football League (NFL) fears a new movie that will be released on December 25, 2015. Team owners in the NFL are already preparing their responses to the movie, “Concussion.”will-smith-concussion-01-600x350

There are a lot people who believe that football cannot survive, including George Visger, a former NFL defensive lineman for the San Francisco 49ers. His comments can be heard in my interview of him two weeks ago during my radio show, “Another Fork in the Road,” on the Brain Injury Radio Network. A rookie linebacker in the NFL resigned after one year of play over fear of brain injury. Already there is a 2.2% decline in participation in high school football, including an even higher rate of decline in Texas, which has led the nation in football players for two decades. One elementary school banned tackling and instituted flag football, to no objections. As more and more parents become aware of the risk of contact sports to the human brain (some will because of this movie), the rate of decline in youth football will increase, and the pool of talented NFL-bound athletes will get smaller. (Full story and trailer)

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SPEAK OUT! NewsBit . . . . . . . . . . . . Simple Blood Test For Traumatic Brain Injury

Simple Blood Test For Traumatic Brain Injury

presented by

Donna O’Donnell Figurski

Newsboy thA simple and convenient test for the existence and severity of a traumatic brain injury (TBI) is badly needed. Currently the only test for a TBI appropriate for use in the Emergency Room is the CT (computerized tomography, often referred to as “CAT”) scan. However, a CT scan can only determine if there is bleeding in the brain. If there isn’t a hemorrhage, the patient is likely to be sent home. Also, a CT scan cannot determine the existence of a concussion. Concussions (even those that do not cause loss of consciousness) are brain injuries that can be harmless and heal, or they can be fatal or cause major life-altering problems. Until now, there has been no way to measure brain damage.

Exciting new results show that the amount of a blood protein (BDNF, brain-derived neurotrophic factor) correlates with the existence of a TBI, when measured within 24 hours of the trauma. Patients with a blood-tube-cartoonTBI had less than one-third the amount of BDNF in their blood than did non-TBI patients. The researchers also found that patients with a TBI who had very low levels of BDNF recovered poorly. This is an exciting beginning because it will be routine to tell if there is brain damage in a person who may have been in an event that could lead to a concussion. A person who has experienced any trauma (like a motor vehicle accident, a sports-related injury, or domestic violence) can now be assessed for brain injury. Appropriate therapies can be considered immediately, instead of waiting for symptoms to appear.

Of interest to current TBI survivors is the possibility that continued BDNF measurements may correlate with the speed of recovery. This correlation needs to be tested – is a BDNF measurement taken months later still meaningful? Also, researchers urgently need to learn the molecular mechanism behind the lowering of BDNF with TBI. Do things that raise the BDNF level allow a patient to recover faster from a TBI? (Interestingly, omega-3 fatty acids and exercise raise BDNF levels.) (Full story)

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