Who said engineering and neuroscience aren’t good bedfellows?

Two University of South Florida professors are proof that disparate disciplines can work together for a common cause – gaining a better understanding of a common health emergency.

Ashwin Parthasarathy, Ph.D., assistant professor in the Department of Electrical Engineering, and Maxim Mokin, M.D., Ph.D., associate professor in the Department of Neurosurgery and Brain Repair, are collaborating on a device that could help prevent strokes in patients during surgery.

(L-r) Dr. Ashwin Parthasarathy, PhD, and Dr. Maxim Mokin, MD, PhD, at Tampa General Hospital as Dr. Parthasarathy tests probes for electrical activity.

“We’re looking to see how new technologies can help drive patient care,’’ Dr. Parthasarathy said of their multi-disciplinary work. “As an engineer, I’m interested in the technology aspect and as a neurologist, Maxim is interested in the medical aspect. But I can address what his needs are and come up with solutions.’’

The engineering department is on the USF campus in northeast Tampa, while much of the work in neurology takes place downtown, at the USF Health South Tampa Center and Tampa General Hospital, USF Health’s primary teaching partner. Traditionally, most teamwork among scientists is done in closer proximity.

“It’s quite rare to be doing this because physically, we don’t even run into each other on campus,’’ Dr. Mokin said. “Engineers live and breathe in their silos and we clinicians don’t get exposed to what they do.’’

The faculty members recently were awarded a two-year, $400,000 research grant from the National Institute of Neurological Disorders and Stroke, a part of the National Institutes of Health. The money will help them collect more quantitative data from their new device, with the goal of improving treatment for patients. They also will purchase tools to refine the technology and make it fully automated, capture more data points, and hire a research coordinator.

“We’re working to make it more robust and easy to use,’’ Dr. Parthasarathy said.

Called a DCS − for diffuse correlation spectroscopy − the optical monitoring tool uses fiber optics to emit light and capture a returning signal. The light monitors blood flow to the brain during surgery and gives real-time information. Any abnormalities in how the light travels alerts doctors to a potential problem, such as a stroke or brain bleed. An explanation of their initial research findings has been published in the Journal of NeuroInterventional Surgery.

For years, neurologists have used MRIs, CAT scans and transcranial dopplers to take images of the brain, but these don’t always give surgeons the information they need at a precise moment. The new, non-invasive device – which has been tested on more than a dozen patients at TGH − uses small plastic caps attached to the head that send real-time data to a monitor in the operating room.

An image of the before (left) and after treatment delivered at Tampa General Hospital.

“The others are good tools but they’re bulky and only give you a snapshot,’’ Dr. Mokin said. “This is a small portable device that studies brain functions in an acute setting, and it gives a continuous recording.’’

The faculty members believe their invention could be a breakthrough in a critical aspect of health care. Each year, nearly 800,000 people in the United States suffer a stroke – one every 40 seconds, according to the American Heart Association. The majority of these incidents are ischemic, meaning blood flow to the brain is reduced or blocked.

“This device is giving us more data to better understand brain signals that might indicate a stroke,’’ Dr. Mokin said. “We need to know more about what is noise, what is normal function, what are the thresholds, and what changes indicate that something bad is about to happen.’’

The more information gathered in the operating room the better, the doctors say, as it will lead to efficiencies on the engineering bench.

“It’s an exciting way to do science,’’ Dr. Parthasarathy said. “I’m able to get instantaneous feedback on how my device is working, so it’s not just me toiling alone in the lab.

“Our hope is to show how this technology has great clinical value, maybe by predicting if a patient is getting better or worse. That’s the end game − predictive value in our measurements.’’

– Story by Kurt Loft for USF Health News; photos by Allison Long, USF Health Communications 

Dr. Christian Bréchot will help elevate biomedical and health-related areas of research excellence to the international level

The former head of the world-renowned Pasteur Institute in Paris has joined USF Health to help university leaders strengthen biomedical and health-related areas of research excellence – and to elevate interdisciplinary signature programs to the international level.

Christian Bréchot, MD, PhD

Preeminent virologist Christian Bréchot, MD, PhD, joined the USF Health Morsani College of Medicine part time in October as senior associate dean for research in global affairs, associate vice president for international partnerships and innovation, and a professor in the Division of Infectious Disease, Department of Internal Medicine.  Dr. Bréchot is also executive director of the Tampa-based Romark Laboratories Institute for Medical Research. Since 2017, he has served as president of the Global Virus Network, a coalition of the world’s foremost medical virologists.

“Dr. Bréchot has been at the forefront of catalyzing teams of top scientists to work together effectively on global solutions for emerging pathogens, malaria and microbial infections,” said Charles Lockwood, MD, senior vice president for USF Health and dean of the Morsani College of Medicine. “He is the ideal person to work with leadership across USF Health and USF in strategically identifying opportunities to take our infectious diseases, cardiovascular, neuroscience, and maternal-child health translational research to the next level, and to build upon the international networks he helped create at the Pasteur Institute and elsewhere to make that happen.”

Before serving as president of the Pasteur Institute from 2013 to 2017, Dr. Bréchot was vice president of medical and scientific affairs at Institut-Merieux, a company that develops new approaches to fight infectious diseases and cancers.  He also served as the general director of Inserm, the French national agency for biomedical research (analogous to the National Institutes of Health in the U.S.) from 2002 to 2007. As professor of hepatology and cell biology at Necker School of Medicine, Paris Descartes University, he headed the clinical department of liver diseases at Necker-Enfants Maldes Hospital from 1997 to 2001.

Dr. Bréchot has authored more than 400 articles in medical and scientific journals, and in 2005 was ranked by the Institute for Scientific Information as the 4^th most cited author on the topic hepatitis C. He has been recognized as an inventor on 18 patents, and helped to create three biotechnology companies.

With a prestigious career bridging basic science and medicine, Dr. Bréchot has combined research, clinical service and teaching with top administrative posts to enhance scientific understanding and better public health. His scholarly endeavors have included cultivating productive public-private partnerships between academia and industry.

During a recent interview in his office at USF Health, Dr. Bréchot talked about leading the Pasteur Institute, a preeminent global network of 33 institutes in 26 countries; his diverse background; and his new role at USF Health.  The interview has been edited for length.

What has been your area of research focus?

As an MD-PhD, I’ve always been convinced of the need to combine basic research with clinical practice — long before translational medicine became fashionable. My basic science research has combined cell biology and molecular virology, mostly focusing on hepatitis B (HBV) and hepatitis C (HCV) and how these viruses can induce liver cancer. I’ve also been very involved in developing diagnostic tests of HBV and HCV and evaluating new drugs to treat chronic forms of the infection.  More recently, I’ve worked on the mechanisms of liver regeneration and based on longstanding research activity in my laboratory, we discovered a new molecule (HIP/PAP, or hepatocarcinoma-intestine-pancreas/pancreatic associated protein), now being tested in clinical trials as a drug that may be useful for patients with a severe form of acute and chronic hepatitis. We’re contemplating organizing new phase 2 clinical trials in China, because China has so many people with chronic hepatitis B infection.

What were some major accomplishments at the Pasteur Institute under your leadership?

First, both at Inserm and the Pasteur Institute, I was very much focused on attracting and supporting young investigators. We created programs and special funding mechanisms to really give scientists at the early stages of their careers the means to develop interdisciplinary research and then get a grant. Second, at Pasteur, we reinforced research activities, especially in the fields of bioinformatics and integrative biology. We created a Center for Bioinformatics, Biostatistics and Integrative Biology (an international multidisciplinary center for processing, analyzing and modeling biological data) that included recruiting 40 high-level engineers and opening a new building.  Third, we merged the activities of different departments focused on the microbiota. For instance, we had a program called Brain and Microbes in which scientists working on infectious agents and those working in the neurosciences looked at how the bacteria of the intestine can modulate brain function, including disorders such as anxiety and depression.

What is the microbiome, and why is it such a hot area of research interest?

The microbiota is made up of populations of bacteria, fungi, certain viruses and other microorganisms present throughout the body.  It’s actually a very old topic:  The first microbiota intervention (to treat diarrhea) was done by a Chinese doctor 3,000 years before Christ (the ancient equivalent of a fecal microbiota transplant). What’s new is our technological progress – with the capacity for genome sequencing and advances in bioinformatics, we now have the possibility to investigate the human microbiota like never before… As a result, we’ve discovered very significant connections between dysbiosis — modifications of how microbe populations are distributed in the gut, the lungs, the skin — and metabolic disorders such as obesity and diabetes, cardiovascular diseases, neurological diseases like Parkinson’s and perhaps also Alzheimer’s, and some infectious diseases where disease severity correlates with what happens to intestinal bacteria. It’s a fascinating, challenging field with applications for cross-disciplinary research and translational medicine, and where international cooperation can be extremely interesting because the link between, say for example, the microbiota and diabetes may be very different in the U.S. and Africa due to the strong influence of environmental factors such as nutrition, as well as genetic variations… So, the science of microbiota as it affects certain diseases is a very good example of a collaboration which, if organized with centers in Africa, Southeast Asia and South America, could create a unique USF program very competitive with other universities.

What attracted you to the University of South Florida?

USF already has a lot of excellent ongoing research activities and in my discussions with senior leadership I found there’s real international ambition here, a desire and commitment to go further. I liked that.

What is your vision for helping advance research at USF Health?

I’m still in the stage where I need to listen and learn more about the research activities to see how I can best contribute. But, initially I want to work with Drs. Lockwood, (Paul) Sanberg, (Stephen) Liggett, (John) Sinnott and other leaders to delineate which strategic research areas need to be reinforced and then contribute to the high-level recruitment of scientists. Second, we’ll increase coordination among different departments working in research areas such as the intestinal microbiota and its impact on cardiovascular, neurodegenerative and infectious diseases. Third, I hope to contribute to the international expansion of USF, building upon the networks from my previous activities including work with industry partners.

I absolutely appreciate that I will only be efficient in helping to advance research activities at USF if I integrate into the team. It’s not always easy, but it works.

Dr. Bréchot will build on global networks from his previous activities, including work with industry partners.

You have said talent is key to research excellence. Is there one predominant quality you seek in selecting top talent?

You start by looking for bright minds. But, when you must choose among five scientists all with very bright minds, enthusiasm and the capacity to integrate are critically important. I’m a fan of soccer where you need to have very talented players, but you also very much need players with team spirit. Modern science needs researchers with an interdisciplinary mode of thinking who interact well with those from other disciplines.

Some things you may not know about Dr. Bréchot:

-Each generation of Dr. Bréchot’s family, dating back to King Louis XIV of France, had at least one medical doctor.

– As a student at Pasteur Institute, he helped set up the first diagnostic test to detect hepatitis B virus in blood; he also taught the first course in molecular biology in China in 1981.

-He met his wife Patrizia Paterlini Bréchot, MD, PhD, a professor of medicine at Necker School of Medicine and founder of a biotech company, when she came from Italy for a postdoctoral fellowship at Necker and Pasteur Institute in Paris. His five grown children include two MD-PhDs: a daughter who is a cancer immunologist at Pennsylvania State University, and a son who directs an intensive care unit at Pitié–Salpêtrière Hospital in Paris, one of Europe’s largest teaching hospitals. There are also six grandchildren, ranging from ages 1 to 11.

-Dr. Bréchot enjoys jogging, playing tennis and snow skiing. Currently, he’s reading about U.S. history, including biographies of George Washington and Abraham Lincoln.

-Photos by Eric Younghans, USF Health Communications and Marketing

10-year study led by USF’s Jerri Edwards concludes computerized brain training program reduces risk of dementia 29 percent

TAMPA, Fla. (Nov. 16, 2017) — Computerized brain training is now the first intervention of any kind to reduce the risk of dementia among older adults. The breakthrough results from a randomized controlled trial were just published in the journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions. The article, “Speed of Processing Training Results in Lower Risk of Dementia,” reports on the latest findings from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study funded by the National Institutes of Health.

Jerri Edwards, PhD

“Speed of processing training resulted in decreased risk of dementia across the 10-year period of, on average, 29 percent as compared to the control,” said lead author Jerri Edwards, PhD, of the University of South Florida Department of Psychiatry and Behavioral Neurosciences and College of Community and Behavioral Sciences. “When we examined the dose-response, we found that those who trained more received more protective benefit.”

The ACTIVE Study enrolled 2,802 healthy older adults at six sites around the United States and followed them for 10 years (as they aged from an average of 74 to 84). Participants were randomized into a control group or one of three intervention arms using different types of cognitive training: 1) a group receiving instruction on memory strategies; 2) a group receiving instruction on reasoning strategies; and 3) a group receiving individualized computerized speed of processing training. Participants in the cognitive training groups were offered 10 initial sessions of training (60-75 minutes per session) which was conducted over the first six weeks of the study.

All participants were assessed on a number of cognitive and functional measures at the beginning of the study, after the first six weeks, and at 1, 2, 3, 5 and 10 years. Subsets of each intervention group also received four additional “booster” training sessions in months 11 and 35 of the study. Researchers found no significant difference in risk of dementia for the strategy-based memory or reasoning training groups, as compared to the control group. However, as compared to the control group, the computerized speed training group showed significantly less risk of dementia – averaging a 29 percent risk reduction.

When reviewing the impact of each computerized speed training session completed, researchers found those who completed more sessions had lower risk. Among those who completed 15 or more sessions across all three intervention groups, the risk of dementia for the computerized speed training group was lowest at 5.9 percent, as compared to 9.7 percent and 10.1 percent for the memory and reasoning groups, respectively. The control group, which did not engage in any training, had a dementia incidence rate of 10.8 percent.

Participants in the computerized speed training group were trained on a highly specific task designed to improve the speed and accuracy of visual attention, including both divided and selective attention exercises. To perform the divided attention training task, a user identified an object (i.e., car or truck) at the center of gaze while at the same time locating a target in the periphery (i.e., car). As the user got the answers correct, the speed of presentation becomes progressively briefer, while the targets become more similar. In the more difficult training tasks, the target in the periphery is obscured by distracting objects, engaging selective attention.

A computerized brain training exercise like that found on BrainHQ.com pushes a user to progressively improve visual speed of processing, with attentional demands both at the center of gaze and periphery.

There is substantial prior scientific literature on this training exercise, which is referred to as “speed of processing training,” “useful field of view training,” or “UFOV training.” The exercise was developed by Dr. Karlene Ball of the University of Alabama Birmingham and Dr. Dan Roenker of Western Kentucky University. It is now exclusively licensed to Posit Science Corporation, and is available as the “Double Decision” exercise of the BrainHQ.com brain training program. |

The paper notes that this particular type of computerized brain training, as updated by its inventors and Posit Science over the years, has previously been shown effective across more than 18 clinical trials in older adults on standard measures of cognitive abilities (e.g., speed of processing and attention) and functional abilities (e.g., maintaining the ability to live independently, depressive symptoms, feelings of control, and health-related quality of life), as well as in real world activities (e.g., driving safety, balance and gait).

“We need to further delineate what makes some computerized cognitive training effective, while other types are not,” said Dr. Edwards. “We also need to investigate what is the appropriate amount of training to get the best results. The timing of intervention is also important. Existing data indicate speed training is effective among older adults with and without mild cognitive impairment, but it is important to understand this is preventative to lower risk of dementia and is not a treatment for dementia. Our ongoing research is examining this intervention among persons with Parkinson’s disease as well as other types of cognitive interventions.”

The preliminary results reported at the Alzheimer’s Association International Conference were confirmed in this report. However, to be more conservative, the publication used a narrower definition of dementia.

The article “Speed of Processing Training Results in Lower Risk of Dementia” reflects the ACTIVE study’s conclusion based on three criteria for dementia: cognitive and functional impairment, outcome of the Mini–Mental State Examination (MMSE) and/or diagnosis of dementia or Alzheimer’s disease as reported by the participant or a relative of the participant. The risk reduction from randomization to speed training ranged from 29 to 33 percent, depending on how dementia was defined.

Older adults interested in participating in similar research can contact the USF Cognitive Aging Laboratory at 813-974-6703.

Watch a demonstration of the speed of processing exercise “Double Decision,” licensed by Posit Science.

ALS mice improved with stem cell therapy; first step for science in finding better treatment  

TAMPA, Fla. (May 12, 2017) – Researchers at the University of South Florida show in a new study that bone marrow stem cell transplants helped improve motor functions and nervous system conditions in mice with the disease amyotrophic lateral sclerosis (ALS) by repairing damage to the  blood-spinal cord barrier.

In a study recently published in the journal Scientific Reports, researchers in USF’s Center of Excellence for Aging and Brain Repair say the results of their experiment are an early step in pursuing stem cells for potential repair of the blood-spinal cord barrier, which has been identified as key in the development of ALS. USF Health Professor Svitlana Garbuzova-Davis, PhD, led the project.

Previous studies in development of various therapeutic approaches for ALS typically used pre-symptomatic mice. This is the first study advancing barrier repair that treats symptomatic mice, which more closely mirrors conditions for human patients, Dr. Garbuzova-Davis said.

Svitlana Garbuzova-Davis, PhD, led the study.

Using stem cells harvested from human bone marrow, researchers transplanted cells into mice modeling ALS and already showing disease symptoms. The transplanted stem cells differentiated and attached to vascular walls of many capillaries, beginning the process of blood-spinal cord barrier repair.

The stem cell treatment delayed the progression of the disease and led to improved motor function in the mice, as well as increased motor neuron cell survival, the study reported.

ALS is a progressive neurodegenerative disease that affects neuronal cells in the brain and the spinal cord, which send signals to control muscles throughout the body. The progressive degeneration of motor neuron cells leads to death from ALS. More than 6,000 Americans each year are diagnosed with the disease.

Because stem cells have the ability to develop into many different cell types in the body, researchers at USF’s Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair have focused on using stem cells to restore function lost through neurodegenerative disorders or injuries.

Damage to the barrier between the blood circulatory system and the central nervous system has been recently recognized as a factor in ALS development, leading researchers to work on targeting the barrier for repair as a potential strategy for ALS therapy.

In this study, the ALS mice were given intravenous treatments of one of three different doses of the bone marrow stem cells. Four weeks after treatment, the scientists determined improved motor function and enhanced motor neuron survival. The mice receiving the higher doses of stem cells fared better in the study, the researcher noted.

The transplanted stem cells had differentiated into endothelial cells – which form the inner lining of a blood vessel, providing a barrier between blood and spinal cord tissue – and attached to capillaries in the spinal cord. Furthermore, the researchers observed reductions in activated glial cells, which contribute to inflammatory processes in ALS.

USF Health Morsani College of Medicine researchers Crupa Kurien, Avery Thomson, Dimitri Falco, Sohaib Ahmad, Joseph Staffetti, George Steiner, Sophia Abraham, Greeshma James, Ajay Mahendrasah, Paul R. Sanberg and Cesario V. Borlongan joined in the project. The study was funded by the National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Read the full study here.

                                                                                                                                                     -USF Health-
USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Physical Therapy and Rehabilitation Sciences, the Biomedical Sciences Graduate and Postdoctoral Programs, and the USF Physicians Group. The University of South Florida, established in 1956 and located in Tampa, is a high-impact, global research university dedicated to student success. USF is ranked in the Top 30 nationally for research expenditures among public universities, according to the National Science Foundation. For more information, visit www.health.usf.edu

News release by Vickie Chachere, USF Research and Innovation

Media contact: 
Anne DeLotto Baier, USF Health Communications
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Lithium salicylate produced steady blood and brain lithium levels up to 48 hours following oral dose, the recent preclinical study showed

Tampa, FL (March 11, 2014) – Lithium, one of the oldest and most widely used drugs to treat neuropsychiatric illnesses, such as bipolar disorder, has a serious drawback – toxicity. In a continued effort to find a safer form of lithium, researchers at the University of South Florida (USF) have discovered that lithium salicylate, an alternative salt form, might be the answer.

The researchers found that oral lithium salicylate produced steady lithium levels up to 48 hours in rats without the toxic spike associated with the rapid absorption of current FDA-approved lithium carbonate.  They concluded that lithium salicylate could be more effective than lithium carbonate, yet without accompanying risks of toxicity, a potentially important development in the next generation of lithium therapeutics.

Their study results appeared in a recent issue of RSC Advances, the journal of the Royal Society of Chemistry.

Douglas Shytle. left, and Adam J. Smith, of the Center of Excellence for Aging and Brain Repair at USF Health, are working on reducing the toxicity of lithium, a drug used to treat bipolar disorder, while enhancing its therapeutic window.

While lithium carbonate has been very effective for the treatment of mania in bipolar disorder, and credited for reducing suicides in depressive phases of the disease, patients who take lithium carbonate are often noncompliant because of adverse effects, including hand tremor, diarrhea, vomiting, weight gain and decreased thyroid function. New drugs that are as effective as lithium carbonate, but without toxicity, have not been forthcoming.

“Despite its narrow therapeutic window and the emergence of proprietary alternatives, U.S. FDA-approved lithium therapeutics are still regarded as the ‘gold standard’ for the treatment of the manic phase of bipolar disorder,” said study lead author Adam J. Smith, PhD, a neuroscientist at the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery, at USF Health.

“Our previous research suggested that re-engineering lithium therapeutics by crystal engineering might produce better performance with reduced toxicities.”

Crystal engineering is the design and synthesis of molecular solid crystal structures with desired properties using intermolecular interactions, Smith said.

The monitor behind Smith in the microscopy lab shows the image of a crystal.

For their latest study published in RSC Advances, the  researchers tested two previously untested salts of lithium — salicylate and lactate — both of which are structurally different from lithium carbonate. In laboratory rats, they found that lithium salicylate and lithium lactate exhibited “profoundly different pharmacokinetics” when compared to the FDA-approved and widely used lithium carbonate. Pharmacokinetics is the way the body absorbs, distributes and gets rid of a drug.

“To our knowledge, this is the first pharmacokinetic study of lithium salicylate and lithium lactate in laboratory animals,” Smith said.

The findings support earlier suggestions that an ideal lithium preparation would be one that would both “flatten” high blood level peaks and also slow declining blood concentrations, the researchers report.

“This is exactly the pharmacokinetic profile produced by lithium salicylate in our study,” said senior author Doug Shytle, PhD, also of the Center of Excellence for Aging and Brain Repair at USF Health. “Remarkably, lithium salicylate produced elevated levels of lithium in the blood and brain 48 hours after the dose, but without the sharp peaks that contribute to the toxicity problems of lithium in the currently used form.”

That 48-hour window, the researchers said, represents a critical difference between lithium salicylate and current FDA-approved lithium therapeutics. If these preclinical results hold true in humans, this would allow for a less frequent dosing regimen and possibly fewer troublesome side effects that plague conventional lithium therapy.

“Psychiatry has long struggled with the fact that, while lithium is highly effective for treating bipolar disorder, the narrow therapeutic window and side effect profile often makes lithium both difficult and sometimes dangerous to work with clinically,” said Todd Gould, MD, of the Department of Psychiatry at the University of Maryland, an expert in the mechanisms of lithium and the neurobiology of bipolar disorder.

“The pharmacokinetic data by Dr. Smith and colleagues suggests that lithium salts other than the commonly used lithium carbonate may have a broader therapeutic window and potentially fewer side effects. Studies in humans will be needed to confirm safety and demonstrate that the pharmacokinetic profile observed in rats is similarly observed in humans.”

USF researchers continue to pursue a safer, more effective lithium therapy, and expect to soon conduct the experiments required to support early clinical trials.

A link to their full study in RSC Advances can be found here: http://pubs.rsc.org/en/content/articlelanding/2014/ra/c3ra46962j#!divAbstract

Smith, A. J., S. Kim, J. Tan, K. B. Sneed, P. R. Sanberg, C. V. Borlongan and R. D. Shytle (2014). “Plasma and brain pharmacokinetics of previously unexplored lithium salts.” RSC Advances 2014, 12362–12365. 

-USF Health-

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation. For more information, visit www.health.usf.edu

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//www.youtube.com/watch?v=wcaOx28CjKg

NT-020, a proprietary supplement including blueberries and green tea, improved cognitive processing speed in clinical trial participants without impaired memory

Tampa, FL (Feb. 6, 2014) – Declines in the underlying brain skills needed to think, remember and learn are normal in aging. In fact, this cognitive decline is a fact of life for most older Americans.

Therapies to improve the cognitive health of older adults are critically important for lessening declines in mental performance as people age. While physical activity and cognitive training are among the efforts aimed at preventing or delaying cognitive decline, dietary modifications and supplements have recently generated considerable interest.

Now a University of South Florida (USF) study reports that a formula of nutrients high in antioxidants and other natural components helped boost the speed at which the brains of older adults processed information.

The USF-developed nutritional supplement, containing extracts from blueberries and green tea combined with vitamin D3 and amino acids, including carnosine, was tested by the USF researchers in a clinical trial enrolling 105 healthy adults, ages 65 to 85.

University of South Florida researchers Paula Bickford, PhD, and Brent Small, PhD, teamed up to investigate the effects of a USF-developed, antioxidant-rich nutritional supplement on the cognitive performance of older adults.

The two-month study evaluated the effects of the formula, called NT-020, on the cognitive performance of these older adults, who had no diagnosed memory disorders.

Those randomized to the group of 52 volunteers receiving NT-020 demonstrated improvements in cognitive processing speed, while the 53 volunteers randomized to receive a placebo did not. Reduced cognitive processing speed, which can slow thinking and learning, has been associated with advancing age, the researchers said.

The study, conducted at the USF Health Byrd Alzheimer’s Institute, appears in the current issue of Rejuvenation Research (Vol. 17 No. 1, 2014).  Participants from both groups took a battery of memory tests before and after the interventions.

“After two months, test results showed modest improvements in two measures of cognitive processing speed for those taking NT-020 compared to those taking placebo,” said Brent Small, PhD, a professor in USF’s School of Aging Studies. “Processing speed is most often affected early on in the course of cognitive aging. Successful performance in processing tasks often underlies more complex cognitive outcomes, such as memory and verbal ability.”

Blueberries, a major ingredient in the NT-020 formula, are rich in polyphenols, a type of antioxidant containing a polyphenolic, or natural phenol substructure.

“The basis for the use of polyphenol-rich nutritional supplements as a moderator of age-related cognitive decline is the age-related increase in oxidative stress and inflammation,” said study co-principal investigator Paula C. Bickford, PhD, a professor in the Department of Neurosurgery and Brain Repair, USF Health Morsani College of Medicine, and senior research career scientist at the James A. Haley Veterans’ Hospital in Tampa. “Non-vitamin polyphenols are the most abundant modulators of oxidative stress and inflammation in our diet. NT-020 is 95 percent polyphenols.”

One of the main ingredients of the supplement, called NT-20, is extracted from blueberries.

In several preclinical trials, researchers gave aging laboratory rats NT-020 to see if it boosted memory and other cognitive performance by promoting the health of neurons in the aging brain. Those studies demonstrated that NT-020 promoted the growth of stem cells in the brain, produced an overall rejuvenating effect, benefitted animals with simulated stroke, and led to better cognitive performance.

The researchers plan future clinical trials with longer intervention periods so that the optimal time for taking the formula may be better understood.  The researchers speculated that if the study had included participants cognitively less healthy, or those with memory impairments, they may have observed “more robust findings.”

“In the future, having markers of oxidative stress and inflammation, as well as brain-based measures of functioning, may allow us to identify the manner by which this compound, as well as others, may influence functioning,” they concluded.

The NT-020 formula was patented by the University of South Florida, in partnership with the James A. Haley Veterans’ Hospital, and licensed to Natura Therapeutics, Inc.  The supplement is commercially available as NutraStem®.

The study was supported by a grant from the University of South Florida Neuroscience Collaborative to Dr. Small and Dr. Bickford.

Dr. Bickford is a co-founder of Natura Therapeutics, Inc.

– USF Health –

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation. For more information, visit www.health.usf.edu

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The USF researchers unexpected finding has implications for treatment of PTSD and related disorders

Low doses of a psychedelic drug erased the conditioned fear response in mice, suggesting that the agent may be a treatment for post-traumatic stress disorder and related conditions, a new study by University of South Florida researchers found.

The unexpected finding was made by a USF team studying the effects of the compound psilocybin on the birth of new neurons in the brain and on learning and short-term memory formation. Their study appeared online June 2 in the journal Experimental Brain Research, in advance of print publication.

Psilocybin, which exerts psychoactive effects, has been isolated from certain mushrooms.

Psilocybin belongs to a class of compounds that stimulate select serotonin receptors in the brain.  It occurs naturally in certain mushrooms that have been used for thousands of years by non-Western cultures in their religious ceremonies.

While past studies indicate psilocybin may alter perception and thinking and elevate mood, the psychoactive substance rarely causes hallucinations in the sense of seeing or hearing things that are not there, particularly in lower to moderate doses.

There has been recent renewed interest in medicine to explore the potential clinical benefit of psilocybin, MDMA and some other psychedelic drugs through carefully monitored, evidence-based research.

“Researchers want to find out if, at lower doses, these drugs could be safe and effective additions to psychotherapy for treatment-resistant psychiatric disorders or adjunct treatments for certain neurological conditions,” said Juan Sanchez-Ramos, MD, PhD, professor of neurology and Helen Ellis Endowed Chair for Parkinson’s Disease Research at the USF Health Morsani College of Medicine.

Dr. Sanchez-Ramos and his colleagues wondered about psilocybin’s role in the formation of short-term memories, since the agent binds to a serotonin receptor in the hippocampus, a region of the brain that gives rise to new neurons. Lead author for this study was neuroscientist Briony Catlow, a former PhD student in Dr. Sanchez-Ramos’ USF laboratory who has since joined the Lieber Institute for Brain Development, a translational neuroscience research center located in the Johns Hopkins Bioscience Park.

The USF researchers investigated how psilocybin affected the formation of memories in mice using a classical conditioning experiment. They expected that psilocybin might help the mice learn more quickly to associate a neutral stimulus with an unpleasant environmental cue.

                        Dr. Juan Sanchez-Ramos

To test the hypothesis, they played an auditory tone, followed by a silent pause before delivering a brief shock similar to static electricity. The mice eventually learned to link the tone with the shock and would freeze, a fear response, whenever they heard the sound.

Later in the study, the researchers played the sound without shocking the mice after each silent pause. They assessed how many times it took for the mice to resume their normal movements, without freezing in anticipation of the shock.

Regardless of the doses administered, neither psilocybin nor ketanserin, a serotonin inhibitor, made a difference in how quickly the mice learned the conditioned fear response.  However, mice receiving low doses of psilocybin lost their fearful response to the sound associated with the unpleasant shock significantly more quickly than mice getting either ketanserin or saline (control group). In addition, only low doses of psilocybin tended to increase the growth of neurons in the hippocampus.

“Psilocybin enhanced forgetting of the unpleasant memory associated with the tone,” Dr. Sanchez-Ramos said. “The mice more quickly dissociated the shock from the stimulus that triggered the fear response and resumed their normal behavior.”

The result suggests that psilocybin or similar compounds may be useful in treating post-traumatic stress disorder or related conditions in which environmental cues trigger debilitating behavior like anxiety or addiction, Dr. Sanchez-Ramos said.

Article citation:

“Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning,” Briony J. Catlow, Shijie Song, Daniel A. Paredes, Cheryl L. Kirstein and Juan Sanchez-Ramos; Experimental Brain Research, published online June 2, 2013; DOI 10.1007/s00221-013-3579-0.

Research with rat models finds chronic inflammation, suppression of cell regeneration, and neuronal cell loss contribute to wide range of motor and cognitive deficits

TAMPA, FL  (Jan. 4, 2013) – Researchers from the University of South Florida and colleagues at the James A. Haley Veterans’ Hospital studying the long-term consequences of traumatic brain injury (TBI) using rat models, have found that, over time, TBI results in progressive brain deterioration characterized by elevated inflammation and suppressed cell regeneration. However, therapeutic intervention, even in the chronic stage of TBI, may still help prevent cell death.

Their study is published online in the current issue of the journal PLOS ONE.

“In the U.S., an estimated 1.7 million people suffer from traumatic brain injury,” said the study’s senior author Cesar V. Borlongan, PhD, professor and vice chair of the Department of Neurosurgery and Brain Repair at USF.  “In addition, TBI is responsible for 52,000 early deaths, accounts for 30 percent of all injury-related deaths, and costs approximately $52 billion yearly to treat.” 

While TBI is generally considered an acute injury, secondary cell death caused by neuroinflammation and an impaired repair mechanism accompany the injury over time, the authors said. Long-term neurological deficits from TBI related to inflammation may cause more severe secondary injuries and predispose long-term survivors to age-related neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and post-traumatic dementia.

Since the U.S. military has been involved in conflicts in Iraq and Afghanistan, the incidence of traumatic brain injury suffered by troops has increased dramatically, primarily from improvised explosive devices (IEDs), according to Martin Steele, Lieutenant General, U.S. Marine Corps (retired), USF associate vice president for veterans research, and executive director of Military Partnerships. In response, the U.S. Veterans Administration has increasingly focused on TBI research and treatment.

Dr. Cesar Borlongan (left), senior author, and Dr. Paul R. Sanberg, co-author

“Progressive injury to hippocampal, cortical and thalamic regions contributes to long-term cognitive damage post-TBI,” said study co-author Paul R. Sanberg,  PhD, DSc, USF senior vice president for research and innovation and executive director of the Center of Excellence for Aging and Brain Repair at USF Health. “Both military and civilian patients have shown functional and cognitive deficits resulting from TBI.”

Because TBI involves both acute and chronic stages, the researchers noted that animal model research on the chronic stages of TBI could provide insight into identifying therapeutic targets for treatment in the post-acute stage.

“Using animal models of TBI, our study investigated the prolonged pathological outcomes of TBI in different parts of the brain, such as the dorsal striatum, thalamus, corpus callosum white matter, hippocampus and cerebral peduncle,” said Dr. Borlongan, principal investigator for the study. “We found that a massive neuroinflammation after TBI causes a second wave of cell death that impairs cell proliferation and impedes the brain’s regenerative capabilities.”

 Upon examining rat brains eight weeks post-trauma, the researchers found “a significant up-regulation of activated microglia cells, not only in the area of direct trauma, but also in adjacent as well as distant areas.”  The location of inflammation correlated with the cell loss and impaired cell proliferation researchers observed.

Microglia cells act as the first and main form of immune defense in the central nervous system and make up 20 percent of the total glial cell population within the brain. They are distributed across large regions throughout the brain and spinal cord.

“Our study found that cell proliferation was significantly affected by a cascade of neuroinflammatory events in chronic TBI and we identified the susceptibility of newly formed cells within neurologic niches and suppression of neurological repair,” wrote the authors.

The researchers concluded that, while the progressive deterioration of the TBI-affected brain over time suppressed efforts of repair, intervention, even in the chronic stage of TBI injury, could help further deterioration.

The study was supported by the U.S. Department of Defense, the USF Signature Interdisciplinary Program in Neuroscience funds, the USF and Veterans Administration Reintegration Funds, and the USF Neuroscience Collaborative Program.

Citation:  Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Grimmig B, et al. (2013) Long-Term Upregulation of Inflammation and Suppression of Cell Proliferation in the Brain of Adult Rats Exposed to Traumatic Brain Injury Using the Controlled Cortical Impact Model. PLOS ONE 8(1): e53376. doi:10.1371/journal.pone.0053376

– About USF – 

The University of South Florida is a high-impact, global research university dedicated to student success. USF ranks 50th in the nation for federal expenditures in research and total expenditures in research among all U.S. universities, public or private, according to the National Science Foundation. Serving more than 47,000 students, the USF System has an annual budget of $1.5 billion and an annual economic impact of $3.7 billion. USF is a member of the Big East Athletic Conference.

News release by Randy Fillmore, special to USF Research News

Media contact:
Judy Lowry, USF Research & Innovation
813-974-3181, or jhlowry@usf.edu

The USF Department of Neurosurgery and Brain Repair was awarded a patent for a spine disc prosthetic device with fusion capability, helping patients with degenerative discs or scoliosis to have a shorter and less painful recovery.

The significance of the device – a pouch filled with beads that is implanted into the spine and functions as a vertebral disc – is that it can be implanted in a less invasive manner and that it allows the spine to more easily fuse to the pouch than it will to other devices currently used.

Co-inventors for the device and the method for using it are: Thomas Freeman, MD, professor of Neurosurgery and medical director of the USF Center for Aging and Brain Repair in the Department of Neurosurgery and Brain Repair, and Wesley Johnson, PhD, a biomechanics engineer who recently retired from the USF Department of Neurosurgery and Brain Repair.

Thomas Freeman, MD,  (left)  and Wesley Johnson, PhD

“The device is unique in the industry because it accommodates conversion from a motion preservation device to a spine fusion device,” Dr. Johnson said.

“It was a device inspired by the late Dr. David Cahill.”

Dr. Cahill, who passed away in 2003, was professor, chairman and founder of the Department of Neurological Surgery at USF. He was an international renowned neurosurgeon and noted for his teaching and his innovation in spinal instrumentation.

“I was hired by Dr. Cahill in the spring of 2003,” Dr. Johnson said. “During my interviews he and I shared our common frustration with the current state of the art.  I reported for my first day and he died the next day in the airplane crash.  I felt a certain sense of satisfaction when the patent was issued.”

Degenerative discs can cause significant pain.

Typically, the options for patients would include removing the problem disc and replacing it with a stiff strut or cage, which could mean additional plates, rods, and screws to stabilize the disc until it heals and the bone fuses across the disc space. But in as many as 20 percent of these procedures, fusion does not occur. In addition, screws and rods can shift, causing serious neurological complications. When fusion does occur, there is a greater likelihood that an adjacent disc then fails.

Motion preservation devices allow more range of motion of the spine than a fusion, Dr. Freeman added.  However, if a standard motion preservation device has to be converted to a fusion for any reason at a later date, this requires a major operation.  The benefit of this new patented device is that it allows for the conversion from a motion preservation device to a fusion device with a simple, quick, minimally invasive procedure that can be performed as an outpatient.

Click here for more information on the patent and device.

Story by Sarah A. Worth, USF Health Office of Communications