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News Article | April 17, 2017
Site: www.prweb.com

With increasing confidence and now a second patent, researchers at a Deerfield, IL medical clinic have developed and are applying a combination therapy that holds promise for millions of Americans suffering from mental depression that is resistant to conventional care. By combining two accepted treatments, innovators led by Steve Best, M.D., director of the Neuroscience Center, Deerfield, IL, have discovered a therapeutic method that benefits even long-troubled patients who suffer conditions ranging from suicidal inclinations to substance abuse and also chronic neuropathic pain. Pain patients have been able to discontinue or dramatically reduce opioid use. Dr. Best, who is also the Medical Director at Abbott House in Highland Park, IL and a member of the board of directors of the Cook County North Suburban affiliate of the National Alliance on Mental Illness, received word of the second patent award during the first week of April, 2017. “The patent granted by the U.S. Patent and Trademark Office is added validation for the combination therapy we are applying when we help patients suffering from mental depression. Very often, the same patients are troubled by chronic pain,” Dr. Best said. Subspecialty-trained in Neuropsychiatry, Dr. Best came to believe that emotional pain and chronic pain are linked and can be addressed most successfully with a combination of two medically accepted therapies. The novelty of Dr. Best’s insight lies in discovering a synergistic effect from the combining of Transcranial Magnetic Stimulation (TMS) applied along with ketamine. According to The Neuroscience Center, the combination therapy can be performed in the outpatient setting, does not require general anesthesia, and has no effect on a patient’s memory. The patented method is reliably effective for the treatment of depression and chronic pain, even for patients who are unable to find relief from conventional therapies and even in cases of substance abuse. Dr. Best and The Neuroscience Center have found that, during the six years of study, as many as ninety percent of the patients have been able to reach some form of remission. "That means the person is able to return to work and leave the disability roll. They’re able to mend broken marriages, families, and resume their lives,” Dr. Best said. “So far, results have lasted up to six years." With medical professionals saying that ten million Americans have mental depression not responding to conventional therapies, and that as many as 40 percent of Americans suffer from chronic pain, why is the promising combination therapy found at a handful of locations worldwide instead of in widespread use? “Medical science is careful and costly,” Dr. Best said. “For example, a small pilot study examining only two forms of the combination can approach one million dollars in cost. Then, if that study involving 40 patients is statistically successful, additional studies will examine new combinations. And so on. We hope for that day. In the meantime, what we are seeing increases our confidence and our enthusiasm.” In addition to the notice of the second patent award, Dr. Best and the researchers are heartened by the growing interest other medical researchers are showing in the combination therapy. During 2016, the world medical community learned of the innovation through reports in a half dozen global medical journals. Dr. Best is also in contact with other U.S. and Brazilian university groups engaged in complementary research paths. “The time is coming when this combination therapy will be utilized proactively and commonly in complex cases to prevent multiple treatment failures,” Dr. Best said. “This will improve the quality of life for millions.” ###


News Article | May 16, 2017
Site: www.sciencedaily.com

Results of a randomized controlled trial show that endovascular treatment (ET) to remove a stroke-causing blood clot in the brain is effective in some patients even when performed within 6 to 24 hours after a stroke. Current guidelines for acute stroke treatment endorse clot removal only when performed within six hours of a stroke. The findings are presented today at the European Stroke Organisation Conference 2017 in Prague. "This still means that you need to be rushed to the hospital as soon as possible after a stroke has occurred because the mantra "time is brain" still holds. However, our study shows that even if treated outside the time window, patients will have significantly reduced disability with clot removal," said Tudor Jovin, M.D., director, UPMC Stroke Institute, and professor of neurology and neurosurgery at the University of Pittsburgh, who co-led the trial. The trial sets a new selection paradigm based on physiology, showing for the first time that looking at patients fulfilling certain imaging and clinical criteria, physiological state of the brain is a much better approach to determining whether patients will benefit from endovascular therapy as opposed to adhering to strict time windows, noted co-principal investigator Raul Nogueira, M.D., professor of neurology, neurosurgery and radiology at Emory University School of Medicine, and director of neuroendovascular service and neurocritical care service at Marcus Stroke & Neuroscience Center, Grady Memorial Hospital. In the study, researchers randomly assigned stroke victims who arrived at the hospital outside the six-hour time window to either receive endovascular therapy or receive only standard medical therapy. Brain imaging and clinical information (neurological deficit) was used to identify and enroll patients who had a small area of irreversibly damaged brain and a significantly larger brain tissue area that was imminently threatened by loss of blood supply, but still alive -- a criterion known as clinical core mismatch. The results showed that almost half of the patients (48.6 percent) receiving endovascular therapy had a good outcome at 90 days after treatment -- defined as the patients being independent in activities of daily living -- showed clinical benefit while only 13.1 percent showed benefit in the group that received clot-busting drugs alone. There was no difference in mortality between the two groups. The researchers planned to enroll 500 patients over the course of the study period. However, an intermediate review of the treatment effectiveness before enrollment was completed led the independent Data Safety Monitoring Board overseeing the study to recommend early termination of the trial after it was demonstrated that ET provided significant clinical benefit in the selected patients. The multi-center international study known as the DAWN trial included trial locations in the United States, Spain, France, Australia and Canada. The trial was sponsored by Stryker Corporation, which manufactures the clot removal devices used in the study.


News Article | May 15, 2017
Site: globenewswire.com

May is nationally recognized by the American Heart Association and the American Stroke Association as stroke awareness month. Stroke is a serious disease that ranks fifth in causes of death and disability when compared to heart disease, cancer, respiratory diseases and accidents. Most strokes are preventable and if treated quickly may make the difference between life and death - or the difference between a full recovery and long-term disability such as paralysis on one side of the body, speech or vision problems or memory loss. When a stroke happens, every second counts – as in the case of David Denmark. David, a 48 year-old homicide detective in Miami-Dade, was at a restaurant one evening when he experienced sudden stroke symptoms.  “All of a sudden I couldn’t move … I couldn’t open my eyes because of the vertigo…and then it went downhill fast, really fast,” he says. He was transported to Baptist Hospital’s Comprehensive Stroke Center where he was met by an expert team led by Sergio Jaramillo, M.D. “When Mr. Denmark entered the Center, we obtained a CT of the brain, assessed him neurologically and came up with a score that tells us how severe the neurological deficit is,” Dr. Jaramillo said, a neurologist with Baptist Health Neuroscience Center.  “If the patient presents within three hours, we can consider them a good candidate for TPA like Mr. Denmark.” TPA is a clot buster, a medicine that breaks up the clot wherever it may be. According to Dr. Jaramillo, David responded remarkably well and within 24 hours all of his neurological symptoms had resolved and there was no evidence he would have any permanent effect on his quality of life. “Every day I wake up and I can move freely. I constantly think what it could have been like. I know how lucky I am,” David says. Dr. Jaramillo goes on to say that “If he hadn’t come to our comprehensive stroke center, there likely would have been some kind of permanent neurological deficit and would have had a negative effect on his quality of life”. That’s why the Joint Commission, which accredits U.S. healthcare organizations, along with the American Heart Association and American Stroke Association, have maintained a unique alliance since 2003 to promote stroke care in hospitals across the nation. More than two years ago, Baptist Hospital in conjunction with Baptist Health Neuroscience Center, joined an elite group of facilities in the United States to be designated by the commission as a Comprehensive Stroke Center. The Joint Commission’s highest level of stroke care, an Advanced Certification, is awarded to those hospitals that have specific abilities to receive and treat the most complex stroke cases. To achieve its status as a Comprehensive Stroke Center, Baptist Hospital underwent a rigorous onsite review by Joint Commission experts. The hospital was shown to have the necessary requirements, including: This month, Baptist Hospital in conjunction with Baptist Health Neuroscience Center was awarded the American Heart Association/American Stroke Association’s top award: Get With The Guidelines®-Stroke Gold Plus Achievement Award with Target: StrokeSM Honor Roll Elite Plus. The award recognizes commitment to providing the most appropriate stroke treatment according to nationally recognized, research-based guidelines based on the latest scientific evidence. Baptist Health Neuroscience Center offers comprehensive and innovative techniques to diagnose and treat the brain, spine and nervous system. Designated as a Comprehensive Stroke Center by The Joint Commission and the American Heart Association and the American Stroke Association, the Center’s philosophy is to provide the most effective care in the least invasive manner. Baptist Health Neuroscience Center is part of Baptist Health South Florida, the largest healthcare organization in the region, with seven hospitals (Baptist Hospital, Baptist Children’s Hospital, Doctors Hospital, Homestead Hospital, Mariners Hospital, South Miami Hospital and West Kendall Baptist Hospital), nearly 50 outpatient and urgent care facilities, Baptist Health Medical Group, Baptist Health Quality Network and internationally renowned centers of excellence. A not-for-profit organization supported by philanthropy and committed to our faith-based charitable mission of medical excellence, Baptist Health has approximately 16,000 employees and 2,300 affiliated physicians. Baptist Health South Florida has been recognized by Fortune as one of the 100 Best Companies to Work For in America and by Ethisphere as one of the World’s Most Ethical Companies. For more information, visit BaptistHealth.net and connect with us on Facebook at facebook.com/BaptistHealthSF and on Twitter and Instagram @BaptistHealthSF. A photo accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/abe1c9c9-32b0-45af-9300-37f685dc0625


News Article | May 15, 2017
Site: globenewswire.com

May is nationally recognized by the American Heart Association and the American Stroke Association as stroke awareness month. Stroke is a serious disease that ranks fifth in causes of death and disability when compared to heart disease, cancer, respiratory diseases and accidents. Most strokes are preventable and if treated quickly may make the difference between life and death - or the difference between a full recovery and long-term disability such as paralysis on one side of the body, speech or vision problems or memory loss. When a stroke happens, every second counts – as in the case of David Denmark. David, a 48 year-old homicide detective in Miami-Dade, was at a restaurant one evening when he experienced sudden stroke symptoms.  “All of a sudden I couldn’t move … I couldn’t open my eyes because of the vertigo…and then it went downhill fast, really fast,” he says. He was transported to Baptist Hospital’s Comprehensive Stroke Center where he was met by an expert team led by Sergio Jaramillo, M.D. “When Mr. Denmark entered the Center, we obtained a CT of the brain, assessed him neurologically and came up with a score that tells us how severe the neurological deficit is,” Dr. Jaramillo said, a neurologist with Baptist Health Neuroscience Center.  “If the patient presents within three hours, we can consider them a good candidate for TPA like Mr. Denmark.” TPA is a clot buster, a medicine that breaks up the clot wherever it may be. According to Dr. Jaramillo, David responded remarkably well and within 24 hours all of his neurological symptoms had resolved and there was no evidence he would have any permanent effect on his quality of life. “Every day I wake up and I can move freely. I constantly think what it could have been like. I know how lucky I am,” David says. Dr. Jaramillo goes on to say that “If he hadn’t come to our comprehensive stroke center, there likely would have been some kind of permanent neurological deficit and would have had a negative effect on his quality of life”. That’s why the Joint Commission, which accredits U.S. healthcare organizations, along with the American Heart Association and American Stroke Association, have maintained a unique alliance since 2003 to promote stroke care in hospitals across the nation. More than two years ago, Baptist Hospital in conjunction with Baptist Health Neuroscience Center, joined an elite group of facilities in the United States to be designated by the commission as a Comprehensive Stroke Center. The Joint Commission’s highest level of stroke care, an Advanced Certification, is awarded to those hospitals that have specific abilities to receive and treat the most complex stroke cases. To achieve its status as a Comprehensive Stroke Center, Baptist Hospital underwent a rigorous onsite review by Joint Commission experts. The hospital was shown to have the necessary requirements, including: This month, Baptist Hospital in conjunction with Baptist Health Neuroscience Center was awarded the American Heart Association/American Stroke Association’s top award: Get With The Guidelines®-Stroke Gold Plus Achievement Award with Target: StrokeSM Honor Roll Elite Plus. The award recognizes commitment to providing the most appropriate stroke treatment according to nationally recognized, research-based guidelines based on the latest scientific evidence. Baptist Health Neuroscience Center offers comprehensive and innovative techniques to diagnose and treat the brain, spine and nervous system. Designated as a Comprehensive Stroke Center by The Joint Commission and the American Heart Association and the American Stroke Association, the Center’s philosophy is to provide the most effective care in the least invasive manner. Baptist Health Neuroscience Center is part of Baptist Health South Florida, the largest healthcare organization in the region, with seven hospitals (Baptist Hospital, Baptist Children’s Hospital, Doctors Hospital, Homestead Hospital, Mariners Hospital, South Miami Hospital and West Kendall Baptist Hospital), nearly 50 outpatient and urgent care facilities, Baptist Health Medical Group, Baptist Health Quality Network and internationally renowned centers of excellence. A not-for-profit organization supported by philanthropy and committed to our faith-based charitable mission of medical excellence, Baptist Health has approximately 16,000 employees and 2,300 affiliated physicians. Baptist Health South Florida has been recognized by Fortune as one of the 100 Best Companies to Work For in America and by Ethisphere as one of the World’s Most Ethical Companies. For more information, visit BaptistHealth.net and connect with us on Facebook at facebook.com/BaptistHealthSF and on Twitter and Instagram @BaptistHealthSF. A photo accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/abe1c9c9-32b0-45af-9300-37f685dc0625


News Article | May 15, 2017
Site: globenewswire.com

May is nationally recognized by the American Heart Association and the American Stroke Association as stroke awareness month. Stroke is a serious disease that ranks fifth in causes of death and disability when compared to heart disease, cancer, respiratory diseases and accidents. Most strokes are preventable and if treated quickly may make the difference between life and death - or the difference between a full recovery and long-term disability such as paralysis on one side of the body, speech or vision problems or memory loss. When a stroke happens, every second counts – as in the case of David Denmark. David, a 48 year-old homicide detective in Miami-Dade, was at a restaurant one evening when he experienced sudden stroke symptoms.  “All of a sudden I couldn’t move … I couldn’t open my eyes because of the vertigo…and then it went downhill fast, really fast,” he says. He was transported to Baptist Hospital’s Comprehensive Stroke Center where he was met by an expert team led by Sergio Jaramillo, M.D. “When Mr. Denmark entered the Center, we obtained a CT of the brain, assessed him neurologically and came up with a score that tells us how severe the neurological deficit is,” Dr. Jaramillo said, a neurologist with Baptist Health Neuroscience Center.  “If the patient presents within three hours, we can consider them a good candidate for TPA like Mr. Denmark.” TPA is a clot buster, a medicine that breaks up the clot wherever it may be. According to Dr. Jaramillo, David responded remarkably well and within 24 hours all of his neurological symptoms had resolved and there was no evidence he would have any permanent effect on his quality of life. “Every day I wake up and I can move freely. I constantly think what it could have been like. I know how lucky I am,” David says. Dr. Jaramillo goes on to say that “If he hadn’t come to our comprehensive stroke center, there likely would have been some kind of permanent neurological deficit and would have had a negative effect on his quality of life”. That’s why the Joint Commission, which accredits U.S. healthcare organizations, along with the American Heart Association and American Stroke Association, have maintained a unique alliance since 2003 to promote stroke care in hospitals across the nation. More than two years ago, Baptist Hospital in conjunction with Baptist Health Neuroscience Center, joined an elite group of facilities in the United States to be designated by the commission as a Comprehensive Stroke Center. The Joint Commission’s highest level of stroke care, an Advanced Certification, is awarded to those hospitals that have specific abilities to receive and treat the most complex stroke cases. To achieve its status as a Comprehensive Stroke Center, Baptist Hospital underwent a rigorous onsite review by Joint Commission experts. The hospital was shown to have the necessary requirements, including: This month, Baptist Hospital in conjunction with Baptist Health Neuroscience Center was awarded the American Heart Association/American Stroke Association’s top award: Get With The Guidelines®-Stroke Gold Plus Achievement Award with Target: StrokeSM Honor Roll Elite Plus. The award recognizes commitment to providing the most appropriate stroke treatment according to nationally recognized, research-based guidelines based on the latest scientific evidence. Baptist Health Neuroscience Center offers comprehensive and innovative techniques to diagnose and treat the brain, spine and nervous system. Designated as a Comprehensive Stroke Center by The Joint Commission and the American Heart Association and the American Stroke Association, the Center’s philosophy is to provide the most effective care in the least invasive manner. Baptist Health Neuroscience Center is part of Baptist Health South Florida, the largest healthcare organization in the region, with seven hospitals (Baptist Hospital, Baptist Children’s Hospital, Doctors Hospital, Homestead Hospital, Mariners Hospital, South Miami Hospital and West Kendall Baptist Hospital), nearly 50 outpatient and urgent care facilities, Baptist Health Medical Group, Baptist Health Quality Network and internationally renowned centers of excellence. A not-for-profit organization supported by philanthropy and committed to our faith-based charitable mission of medical excellence, Baptist Health has approximately 16,000 employees and 2,300 affiliated physicians. Baptist Health South Florida has been recognized by Fortune as one of the 100 Best Companies to Work For in America and by Ethisphere as one of the World’s Most Ethical Companies. For more information, visit BaptistHealth.net and connect with us on Facebook at facebook.com/BaptistHealthSF and on Twitter and Instagram @BaptistHealthSF. A photo accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/abe1c9c9-32b0-45af-9300-37f685dc0625


News Article | May 16, 2017
Site: www.eurekalert.org

PITTSBURGH, May 16, 2017 - Results of a randomized controlled trial show that endovascular treatment (ET) to remove a stroke-causing blood clot in the brain is effective in some patients even when performed within 6 to 24 hours after a stroke. Current guidelines for acute stroke treatment endorse clot removal only when performed within six hours of a stroke. The findings are presented today at the European Stroke Organisation Conference 2017 in Prague. "This still means that you need to be rushed to the hospital as soon as possible after a stroke has occurred because the mantra "time is brain" still holds. However, our study shows that even if treated outside the time window, patients will have significantly reduced disability with clot removal," said Tudor Jovin, M.D., director, UPMC Stroke Institute, and professor of neurology and neurosurgery at the University of Pittsburgh, who co-led the trial. The trial sets a new selection paradigm based on physiology, showing for the first time that looking at patients fulfilling certain imaging and clinical criteria, physiological state of the brain is a much better approach to determining whether patients will benefit from endovascular therapy as opposed to adhering to strict time windows, noted co-principal investigator Raul Nogueira, M.D., professor of neurology, neurosurgery and radiology at Emory University School of Medicine, and director of neuroendovascular service and neurocritical care service at Marcus Stroke & Neuroscience Center, Grady Memorial Hospital. In the study, researchers randomly assigned stroke victims who arrived at the hospital outside the six-hour time window to either receive endovascular therapy or receive only standard medical therapy. Brain imaging and clinical information (neurological deficit) was used to identify and enroll patients who had a small area of irreversibly damaged brain and a significantly larger brain tissue area that was imminently threatened by loss of blood supply, but still alive--a criterion known as clinical core mismatch. The results showed that almost half of the patients (48.6 percent) receiving endovascular therapy had a good outcome at 90 days after treatment--defined as the patients being independent in activities of daily living--showed clinical benefit while only 13.1 percent showed benefit in the group that received clot-busting drugs alone. There was no difference in mortality between the two groups. The researchers planned to enroll 500 patients over the course of the study period. However, an intermediate review of the treatment effectiveness before enrollment was completed led the independent Data Safety Monitoring Board overseeing the study to recommend early termination of the trial after it was demonstrated that ET provided significant clinical benefit in the selected patients. The multi-center international study known as the DAWN trial included trial locations in the United States, Spain, France, Australia and Canada. The trial was sponsored by Stryker Corporation, which manufactures the clot removal devices used in the study. A $14 billion world-renowned health care provider and insurer, Pittsburgh-based UPMC is inventing new models of patient-centered, cost-effective, accountable care. UPMC provides nearly $900 million a year in benefits to its communities, including more care to the region's most vulnerable citizens than any other health care institution. The largest nongovernmental employer in Pennsylvania, UPMC integrates 65,000 employees, more than 25 hospitals, 600 doctors' offices and outpatient sites, and a more than 3.2 million-member Insurance Services Division, the largest medical and behavioral health services insurer in western Pennsylvania. Affiliated with the University of Pittsburgh Schools of the Health Sciences, UPMC ranks No. 12 in the prestigious U.S. News & World Report annual Honor Roll of America's Best Hospitals. UPMC Enterprises functions as the innovation and commercialization arm of UPMC while UPMC International provides hands-on health care and management services with partners in 12 countries on four continents. For more information, go to UPMC.com. As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www. .


Lukiw W.J.,Neuroscience Center
Experimental Neurology | Year: 2012

Micro RNAs (miRNAs), small and labile ~. 22 nucleotide-sized fragments of single stranded RNA, are important regulators of messenger (mRNA) complexity and in shaping the transcriptome of a cell. In this communication, we utilized amyloid beta 42 (Aβ42) peptides and interleukin-1beta (IL-1β) as a combinatorial, physiologically-relevant stress to induce miRNAs in human primary neural (HNG) cells (a co-culture of neurons and astroglia). Specific miRNA up-regulation was monitored using miRNA arrays, Northern micro-dot blots and RT-PCR. Selective NF-k{cyrillic}B translocation and DNA binding inhibitors, including the chelator and anti-oxidant pyrollidine dithiocarbamate (PDTC) and the polyphenolic resveratrol analog CAY10512 (trans-3,5,4'-trihydroxystilbene), indicated the NF-k{cyrillic}B sensitivity of several brain miRNAs, including miRNA-9, miRNA-125b and miRNA-146a. The inducible miRNA-125b and miRNA-146a, and their verified mRNA targets, including 15-lipoxygenase (15-LOX), synapsin-2 (SYN-2), complement factor H (CFH) and tetraspanin-12 (TSPAN12), suggests complex and highly interactive roles for NF-k{cyrillic}B, miRNA-125b and miRNA-146a. These data further indicate that just two NF-k{cyrillic}B-mediated miRNAs have tremendous potential to contribute to the regulation of neurotrophic support, synaptogenesis, neuroinflammation, innate immune signaling and amyloidogenesis in stressed primary neural cells of the human brain. © 2011 Elsevier Inc..


News Article | February 22, 2017
Site: www.eurekalert.org

Published today in Nature, the discovery has major implications for the study of motivation, decision making, as well as addiction and other disorders CHAPEL HILL, NC - The prefrontal cortex, a large and recently evolved structure that wraps the front of the brain, has powerful "executive" control over behavior, particularly in humans. The details of how it exerts that control have been elusive, but UNC School of Medicine scientists, publishing today in Nature, have now uncovered some of those details, using sophisticated techniques for recording and controlling the activity of neurons in live mice. The UNC scientists, led by Garret Stuber, PhD, associate professor in UNC's departments of psychiatry and cell biology & physiology, examined two distinct populations of prefrontal neurons, each of which project to a different brain region outside the cortex. The researchers found that as mice learn to associate a particular sound with a rewarding sugary drink, one set of prefrontal neurons becomes more active and promotes what researchers call reward-seeking behavior - a sign of greater motivation. By contrast, other prefrontal neurons are silenced in response to the tone, and those neurons act like a brake on reward-seeking. "We've known that there are a lot of differences in how prefrontal neurons respond to stimuli, but nobody has really been able to map these differences onto the intrinsic wiring of the brain," said Stuber, senior author of the study and member of the UNC Neuroscience Center. Stuber and colleagues obtained their findings with the use of three sophisticated and relatively new neuroscience tools: deep-brain two-photon imaging, optogenetics, and genetic techniques for labeling neurons by their projection targets in the brain. The successful combination of these tools heralds their future common use in defining the pathways and functions of many other brain networks to help uncover the roots of both normal and abnormal behavior. The study, conducted by first authors and UNC postdoctoral fellows James Otis, PhD, and Vijay Namboodiri, PhD, focused on the dorsomedial (upper-middle) prefrontal cortex, or dmPFC. "This region is critical for reward processing, decision making, and cognitive flexibility among other things, but how distinct populations of neurons within dmPFC orchestrate such phenomena were unclear," Stuber said. Stuber and colleagues examined how the activity of dmPFC neurons changes during a Pavlovian reward-conditioning process. In this process, mice learn to associate an auditory tone with a taste of sugary liquid until the tone itself is enough to make the animals start licking around their mouths in anticipation. "This simple experiment models a learning phenomenon that occurs in lots of different brain regions," Stuber said. "It is critical for motivation and decision making, and of course it can go awry in drug and food addiction, depression, and other neuropsychiatric disorders." As the mice in the experiment learned to associate the tone with the sweet drink, the researchers found that a subset of the mouse dmPFC neurons became increasingly excited when the tone sounded, whereas another subset went increasingly silent. The researchers were able to observe this phenomenon by using a deep-brain version of two-photon imaging, a technique in which a microscope visualizes hundreds of brain cells simultaneously in mice that are awake and able to perform some ordinary behaviors. The dmPFC is known to output many of its chemical signals to two other brain regions, the nucleus accumbens (NAc) and the paraventricular nucleus of the thalamus (PVT), both of which are considered important for reward-directed behavior. Stuber's team found that the NAc-projecting neurons in the dmPFC were the ones that became increasingly excited by the tone, and the PVT-projecting neurons were the ones that became increasingly suppressed. The two sets of neurons turned out to be physically separate within the dmPFC only by a few hundred micrometers. The team then used optogenetic techniques to artificially drive the activities of these neurons. Optogenetics allows researchers to use beams of light to activate specific populations of neurons. Driving the NAc-projecting neurons caused the mice to anticipate their sweet reward more intensely, with more licks after the tone. By contrast, driving the PVT-projecting neurons muted that anticipatory, reward-seeking behavior. The findings represent a basic demonstration of how the dmPFC has evolved anatomically distinct neuronal populations that have functionally distinct control over behavior, Stuber said. And the discovery points to the existence of similar combinations of control mechanisms elsewhere in the brain. He and his colleagues are now following up with studies of dmPFC neurons that project to other brain regions. Other co-authors were UNC undergraduate students Ana M. Matan and Emily P. Mohorn, visiting graduate student from the university of Utrecht Elisa Voets, UNC MD/PhD student Elliot Robinson, Stuber lab manager Oksana Kosyk, and UNC postdoctoral researchers Jenna A. McHenry, PhD, Shanna L. Resendez, PhD, and Mark A. Rossi, PhD, all of the Stuber lab. Funding was provided by the National Institutes of Health, the Brain and Behavior Research Foundation, the Children's Tumor Foundation, and the Foundation of Hope.


News Article | February 27, 2017
Site: www.eurekalert.org

Prolonged epileptic seizures may cause serious problems that will continue for the rest of a patient's life. As a result of a seizure, neural connections of the brain may be rewired in an incorrect way. This may result in seizures that are difficult to control with medication. Mechanisms underlying this phenomenon are not entirely known, which makes current therapies ineffective in some patients. A study conducted with a rat epilepsy model at the Neuroscience Center of the University of Helsinki showed that a change in the function of gamma-aminobutyric acid (GABA), a main neurotransmitter in the brain, is an underlying cause in the creation of harmful neural connections. After a prolonged convulsive seizure, instead of the usual inhibitory effect of the transmitter, GABA accelerates brain activity. This, in turn, creates new, harmful neural connections, says Research Director Claudio Rivera. The accelerating effect of GABA was blocked for three days with a drug called bumetanide given soon after a seizure. Two months after the seizure, the number of harmful connections detected in the brain was significantly lower. "Most importantly, the number of convulsive seizures diminished markedly," says Claudio Rivera. In this study, new indications may be found for bumetanide in the treatment of epilepsy. Bumetanide is a diuretic already in clinical use. Extensive clinical studies have already been conducted with bumetanide regarding its ability to reduce the amount of convulsions or prevent them entirely in the acute phase of seizures. This, however, is the first time that bumetanide has been found to have a long-term effect on the neural network structure of the brain. Further study of the newly found mechanism may eventually help limit the exacerbation of epilepsy and prevent the onset of permanent epilepsy after an individual serious seizure. It may also be possible that a similar mechanism is responsible for the onset of epilepsy after a traumatic brain injury. "The next step is to study bumetanide both by itself and in combination with other clinically used drugs. We want to find out the ways in which it may offer additional benefits in the treatment of epilepsy in combination with and even in place of currently used antiepileptic drugs," says Claudio Rivera.


Lukiw W.J.,Neuroscience Center
Alzheimer's Research and Therapy | Year: 2012

Abundant neurochemical, neuropathological, and genetic evidence suggests that a critical number of proinflammatory and innate immune system-associated factors are involved in the underlying pathological pathways that drive the sporadic Alzheimer's disease (AD) process. Most recently, a series of epigenetic factors - including a select family of inducible, proinflammatory, NF-κB-regulated small noncoding RNAs called miRNAs - have been shown to be significantly elevated in abundance in AD brain. These upregulated miRNAs appear to be instrumental in reshaping the human brain transcriptome. This reorganization of mRNA speciation and complexity in turn drives proinflammatory and pathogenic gene expression programs. The ensuing, progressively altered immune and inflammatory signaling patterns in AD brain support immunopathogenetic events and proinflammatory features of the AD phenotype. This report will briefly review what is known concerning NF-κB-inducible miRNAs that are significantly upregulated in AD-targeted anatomical regions of degenerating human brain cells and tissues. Quenching of NF-κB-sensitive inflammatory miRNA signaling using NF-κB-inhibitors such as the polyphenolic resveratrol analog trans-3,5,4′-trihydroxystilbene (CAY10512) may have some therapeutic value in reducing inflammatory neurodegeneration. Antagonism of NF-κB-inducing, and hence proinflammatory, epigenetic and environmental factors, such as the neurotrophic herpes simplex virus-1 and exposure to the potent neurotoxin aluminum, are briefly discussed. Early reports further indicate that miRNA neutralization employing anti-miRNA (antagomir) strategies may hold future promise in the clinical management of this insidious neurological disorder and expanding healthcare concern. © 2012 BioMed Central Ltd.

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