Researchers have identified a new way to promote recovery after spinal cord injury with an advance in stem-cell technology. A study conducted by members of the New York State Center of Research Excellence in Spinal Cord Injury and published today in the open access journal Journal of Biology reveals that rats recover from spinal cord injury following transplantation with immature support cells of the central nervous system generated from stem cells. Transplanting immature support cells called astrocytes, which were first generated in tissue culture from stem cell-like cells called glial restricted precursors, resulted in much better outcomes for spinal cord repair than just transplanting stem cells alone. This result challenges current ideas of how to use stem cells to promote tissue repair.

The research team led by Stephen Davies from Baylor College of Medicine, Houston, USA and colleagues from the University of Rochester Medical Center, New York, USA took embryonic glial precursor cells and induced them to differentiate in culture into a specific type of embryonic astrocyte known to be highly supportive of nerve fibre growth. They hoped these cells would have the repair capabilities of the embryonic spinal cord, which is lost in adults. Davies et al. transplanted these cells into cuts in the spinal cord of adult rats and measured the growth of nerve fibres by labelling them with a dye. They then compared healing and recovery in these rats with the recovery in spinal cord injured rats that received either undifferentiated glial precursor cells or no treatment at all.

Davies et al.’s results show that transplants of the precursor-derived astrocytes promoted the rapid growth of 40% of sensory nerve fibres across the cuts. The transplanted cells also suppressed the formation of scar tissue and aligned damaged tissue at the injury site. Furthermore, neurons in the brain that normally degenerate if their nerve fibres are severed in the spinal cord, were rescued when their cut nerve fibres interacted with the astrocytes transplanted into spinal cord injuries. In contrast, transplanted precursor cells failed to suppress scar formation or promote the growth of any nerve fibres across the injury site. Importantly, in a sensitive test of limb placement during walking, rats that received the astrocyte transplants recovered and were able to walk normally within two weeks, whereas the other rats that received undifferentiated precursor cells did not recover at all and still had difficulties with walking four weeks after the surgery.

These studies make important advances in both stem cell technology and identification of the right cell types for repairing the injured adult nervous system.

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Article:
Astrocytes derived from glial-restricted precursors promote spinal cord repair
Jeannette E Davies, Carol Huang, Christoph Proschel, Mark Noble, Margot Mayer-Proschel and Stephen JA Davies
Journal of Biology 2006, 5:7 (April 2006)

Contact: Juliette Savin
BioMed Central

Aerobic training is associated with a reversal of abnormal hormonal patterns that underlie many of the debilitating symptoms of heart failure, according to a new study in the May 2, 2006, issue of the Journal of the American College of Cardiology.

“A feasible home-based and progressively adjusted aerobic training strategy is able to overcome the limitation of pharmacological treatment in antagonizing neurohormonal activation in heart failure patients, likely contributing to a significant improvement in quality of life, and possibly to the positive prognostic effects,” said Claudio Passino, M.D. from the CNR Institute of Clinical Physiology in Pisa, Italy.

It is well-known that exercise training helps many heart failure patients feel better and improves their ability to function more normally. This study indicates that aerobic training may produce these benefits by reversing the abnormal production of certain neurohormones that result in many of the severe symptoms of heart failure.

After a heart attack or other cardiac event, the body responds by increasing the production of B-type natriuretic peptide (BNP). This neurohormonal activation, as it is called, helps the heart continue to pump blood in the short run by constricting blood vessel and retaining sodium in cardiac cells.

“This neurohormonal imbalance becomes detrimental on the long-term, promoting left ventricular fibrosis, dilatation, arrhythmias, peripheral tissue hypoperfusion, edemas, and thus leading to a symptomatic disease with dyspnea and fatigue,” Dr. Passino said.

Previous studies indicated that patients with higher levels of B-type natriuretic peptide have poorer prognoses. Drug treatments are often unable to adequately reverse the neurohormonal activation.

Since physical activity often helps heart failure patients, the researchers wanted to find out what effect aerobic training has on the neurohormonal imbalance. They randomized heart failure patients into two groups. The treatment group consisted of 47 patients who entered a nine-month aerobic training program that progressively increased the amount of work the patients were able to perform. The control group of 48 patients received standard heart failure treatments, but no physical training.

The 44 patients who completed the training program improved their fitness and said their quality of life was better than the 41 patients who completed the control group arm of the study. But in addition, the patients who worked out had decreased levels of three key hormones, B-type natriuretic peptide (BNP), amino-terminal pro-brain natriuretic peptide (NT-proBNP), and norepinephrine.

Dr. Passino said the results indicate that aerobic training may be able to restore neurohormonal balance in a way that may improve on current drug therapies.

“Reversing neurohormonal activation by physical training adds to the current clinical practice a novel non-pharmacological aid. Out of 85 patients who completed the protocol, only the 44 randomized to the training program improved functional capacity, systolic function, and quality of life, in contrast to the controls. These beneficial effects were associated with a decrease in plasma level of BNP, NT-proBNP, and norepinephrine, only in the training group,” he said.

In addition, he said that the measurements of neurohormonal activation used in this study may be a useful way for physicians to assess the effect of training in their patients.

John Floras, M.D., D.Phil., F.R.C.P.C. from the University of Toronto in Canada, who was not connected with this study, said the results provide additional evidence of the benefits of exercise for selected heart failure patients, while offering fresh insight into how training works to provide those benefits.

“While an acute bout of exercise will lead to increases in both norepinephrine and BNP, with chronic training plasma concentrations of these factors diminish, suggesting that exercise training modulates beneficially activation of several neurohumoral pathways that reflect the severity of heart failure, and that following BNP concentrations may be one way of assuring that long term exercise training programs are having beneficial effects in individual patients. Pending is evidence from large randomized clinical trials that such short term changes will translate, over time, into mortality benefits for patients with chronic heart failure,” Dr. Floras said.

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Disclosure Box

Sources quoted in this news release do not report any potential conflicts of interest regarding this topic.

Contact: Amy Murphy
American College of Cardiology

Researchers believe they have identified a new way, using an advance in stem-cell technology, to promote recovery after spinal cord injury of rats, according to a study published in today’s Journal of Biology.

Scientists from the New York State Center of Research Excellence in Spinal Cord Injury showed that rats receiving a transplant of a certain type of immature support cell from the central nervous system (generated from stem cells) had more than 60 percent of their sensory nerve fibers regenerate. Just as importantly, the study showed that more than two-thirds of the nerve fibers grew all the way through the injury sites eight days later, a result that is much more promising than previous research. The rats that received the cell transplants also walked normally in two weeks.

The University of Rochester Medical Center, Rochester, N.Y., and Baylor College of Medicine, Houston, collaborated on the work. Researchers believe they made an important advance in stem cell technology by focusing on a new cell type that appears to have the capability of repairing the adult nervous system.

“These studies provide a way to make cells do what we want them to do, instead of simply putting stem cells into the damaged area and hoping the injury will cause the stem cells to turn into the most useful cell types,” explains Mark Noble, Ph.D., co-author of the paper, professor of Genetics at the University of Rochester, and a pioneer in the field of stem cell research. “It really changes the way we think about this problem.”

The breakthrough is based on many years of stem cell biology research led by Margot Mayer-Proschel, Ph.D., associate professor of Genetics at the University of Rochester. In the laboratory, Mayer-Proschel and colleagues took embryonic glial stem cells and induced them to change into a specific type of support cell called an astrocyte, which is known to be highly supportive of nerve fiber growth. These astrocytes, called glial precursor-derived astrocytes or GDAs, were then transplanted into the injured spinal cords of adult rats. Healing and recovery of the GDA rats was compared to other injured rats that received either no treatment at all or treatment with undifferentiated stem cells.

The rats without the GDA cell transplant did not show any nerve fiber regeneration and still had difficulty walking four weeks after surgery.

“We demonstrated that we can treat these precursor cells, in culture, with signals we know to be important in the development of astrocytes and push these stem cell-like cells down a pathway that supports regeneration of the nervous system,” said Stephen Davies, Ph.D., the study’s lead investigator and assistant professor of Neurosurgery at Baylor.

“At the heart of stem cell transplantation research is finding the right cell for the right job,” Noble added. “In this case the work of this team has identified a cell that provides many more benefits than those seen with other cell types and thus, it gives us hope that we are on a better track.”

The GDA cells seem to work by signaling the tissue to repair in several ways, such as by suppressing scar tissue, rescuing motor pathway neurons in the brain and aligning damaged tissue at the injured site. More investigation is needed, however, before the new technology could be used in humans, researchers said.

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The New York State Spinal Injury Program funded the research, as well as the National Institutes of Health and the Christopher Reeve Foundation.

Co-authors from the University of Rochester are Noble, Mayer-Proschel and Chris Proschel. In addition to Davies, co-authors from Baylor’s Department of Neurosurgery are Jeannette E. Davies and Carol Huang. All of the scientists are all members of the New York State Center of Research Excellence in Spinal Cord Injury.

Contact: Leslie Orr
University of Rochester Medical Center

While many treatment approaches were found helpful, the authors report that the patients who were most successful in abstaining from alcohol 16 weeks after treatment were those prescribed naltrexone under medical management and those participating in a multi-session program of alcohol counseling delivered by a behavioral specialist.

The paper appears in the May issue of the Journal of the American Medical Association and reports on the largest clinical trial ever conducted of pharmacologic and behavioral treatments for alcohol dependence.

“The most robust finding in the study is that those receiving any medication did much better than those who received no pills at all,” says The Scripps Research Institute’s Professor Barbara Mason, an author of the paper. “This should be a wakeup call. With less than one percent of those seeking help for alcohol dependence receiving a prescription, medication is underutilized. Medication for alcoholism can offer patients an advantage for their recovery, especially in a real-world setting.”

Another important aspect of the study, says Mason, is that it offers new safety data on the prescription drugs used in the trial, naltrexone and acamprosate, which were administered at higher-than-standard doses. “We had no serious drug-related events during the course of the research,” she says. “That fact should offer prescribing physicians a high degree of comfort.”

About eight million individuals in the United States currently meet the diagnostic criteria for alcohol dependence, also called alcoholism, a leading preventable cause of morbidity and mortality and a major contributor to health care costs, according to the paper’s background information. In primary care settings, the prevalence of alcohol use disorders ranges from 20 percent to 36 percent.

While several behavioral treatment programs and drugs now approved by the U.S. Food and Drug Administration had been shown effective for treating alcohol dependence in previous studies, no large-scale randomized controlled study had evaluated whether combined drug treatment with or without behavioral therapy could improve outcome. In 2001, the National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, launched “Combining Medications and Behavioral Interventions for Alcoholism” (COMBINE) to identify the most effective current treatments and treatment combinations.

The trial, conducted at 11 sites around the country from January 2001 to January 2004, recruited and randomly assigned 1,383 recently abstinent alcohol dependent patients.

Individuals were assigned to one of nine treatment groups. In eight of the nine groups, patients received what the paper called “medical management,” attending sessions with a physician, nurse, physicians assistant, or pharmacist where these health care professionals reviewed the diagnosis, recommended abstinence and mutual-help participation, and reviewed patients’ progress. Some groups also received pills: naltrexone (100 milligrams a day), acamprosate (3 grams a day), both naltrexone and acamprosate, or placebos. Four groups also received “Combined Behavioral Intervention (CBI)”-an alcohol counseling program with a behavioral specialist that was offered in up to 20 50-minute sessions. A ninth group received the specialized counseling, but no pills.

Patients were assessed during the 16 weeks of active treatment and one year after treatment.

Contrary to expectation, neither combining naltrexone with the medication acamprosate nor combining naltrexone with the program’s specialized behavioral treatment provided an additive benefit to taking naltrexone alone.

Also contrary to expectation, the medication acamprosate was shown similar to placebo in this trial. Mason comments, “Previous studies have shown that acamprosate alone and in combination with naltrexone can work in settings that reflect clinical practice. The COMBINE trial involved a 4.5-hour intake session and follow-up sessions of up to two hours, as well as contact with up to five specialized staff persons at every visit. This may have increased placebo response such that differences between drugs were very small, even with naltrexone, so I would interpret these outcomes with caution for use in a real-world setting.”

Mason-who is co-director of the Pearson Center for Alcoholism and Addiction Research at Scripps Research, director of Scripps Research’s Division of Psychopharmacology of the Molecular and Integrative Neurosciences Department, and adjunct faculty at University of Miami School of Medicine and Rockefeller University-is currently conducting ancillary studies to the COMBINE trial at Scripps Research.

Mason’s laboratory explores the physiological changes in the brain that drive excessive drinking and create vulnerability to relapse. She also investigates the viability of using new compounds to modulate the neurological effects of alcohol, reduce excessive intake, and prevent relapse. Those interested in participating in one of her clinical trial studies at the Scripps Research La Jolla campus should call (858) 784-7867.

The COMBINE paper, titled “Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence,” appears in the May 2 issue of the Journal of the American Medical Association (285: 2075-2076). In addition to Mason, the study’s authors are: Raymond F. Anton, Stephanie S. O’Malley, Domenic A. Ciraulo, Ron A. Cisler, David Couper, Dennis M. Donovan, James D. Hosking, Bankole A. Johnson, Joseph LoCastro, Richard Longabaugh, Margaret E. Mattson, William R. Miller, Helen M. Pettinati, Carrie L. Randall, Robert Swift, Roger D. Weiss, Lauren D. Williams, and Allen Zweben.

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About The Scripps Research Institute
The Scripps Research Institute, headquartered in La Jolla, California, in 18 buildings on 40 acres overlooking the Pacific Ocean, is one of the world’s largest independent, non-profit biomedical research organizations. It stands at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel.

Scripps Florida, a 364,000 square-foot, state-of-the-art biomedical research facility, will be built in Palm Beach County. The facility will focus on basic biomedical science, drug discovery, and technology development. Palm Beach County and the State of Florida have provided start-up economic packages for development, building, staffing, and equipping the campus. Scripps Florida now operates with approximately 160 scientists, technicians, and administrative staff at 40,000 square-foot lab facilities on the Florida Atlantic University campus in Jupiter.

Contact: Keith McKeown
Scripps Research Institute

View drug information on Naltrexone Hydrochloride Tablets.

UCLA researchers discovered how an experimental drug, called Ro15-4513, binds to specific receptors on brain neurons, which helps explain how this drug stops the drunken behavioral symptoms of alcohol such as impaired motor coordination, memory loss and drowsiness.

The team showed in the lab that Ro15-4513 binds to and blocks alcohol action on these highly alcohol-sensitive receptors. The UCLA group previously found that these receptors are specific subtypes of Gamma-amino butyric acid (GABA-A) receptors that play a role in impairing motor coordination caused by alcohol in experimental animals.

IMPACT: These studies are the first to show how the alcohol antidote drug Ro15-4513 binds to these GABA-A receptors. The research may lead to a better understanding of how alcohol works in the brain as well as help develop drugs that prevent alcohol actions such as a sober-up pill, and alcohol addiction medications and treatments. UCLA researchers also suggest in the future that it may be possible to harness the beneficial effects of alcohol on the body, including inducing sleep, enhancing mood or mirroring the positive effects of moderate alcohol consumption on the heart and brain.

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AUTHORS: Richard W. Olsen, Ph.D., professor and Martin Wallner, Ph.D., researcher, both in the UCLA Department of Molecular and Medical Pharmacology, are available for interviews.

JOURNAL: The research appears in the May 8 online edition of the Proceedings of the National Academy of Sciences. A PDF of the full study is available.

FUNDING: The study was funded by the National Institutes of Health, the Alcoholic Beverage Medical Research Foundation, and the State of California for medical research on alcohol and substance abuse.

Contact: Rachel Champeau
University of California – Los Angeles

This study examined whether muscle vibration enhances the brain’s ability to control voluntary movement. Sixteen healthy men and women participated in studies involving the application of 15 or 30 minutes of vibration to the wrist extensor muscle. Fifteen minutes of vibration significantly increased muscle twitch responses, which indicates increased output to the muscles. The effects of muscle vibration were not sustained after 20 minutes. These data provide a basis for exploring the effectiveness of muscle vibration in improving muscle function in people with central motor disorders such as stroke.

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Highlight from JRRD pg. 787

Contact: Dr. Stacieann Yuhasz
yuhaszvard
VA Research Communications Service

Shock-absorbing pylons (SAP) are as effective as rigid pylons for people with below-the-knee amputations. In this study, a commonly prescribed SAP is compared to a conventional rigid pylon. The pylons were assessed for effect on gait mechanics, transmitted accelerations, and functional outcomes using step counts and questionnaires. The only statistically significant finding was for the prosthetic-side knee angle at initial contact. Volunteers displayed an average of 2.6В° more flexion with the rigid pylon than the SAP while walking at a controlled speed. This result indicates that individuals with below-the-knee amputations can adjust the stiffness of their residual limb in response to changes in prosthetic component stiffness.

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Highlight from JRRD pg. 795

Contact: Dr. Stacieann Yuhasz
yuhaszvard
VA Research Communications Service

The amount of time teenagers spend in front of TV screens and monitors has been associated with physical complaints. A large study of more than 30,000 Nordic teenagers published in the open access journal BMC Public Health has shown that TV viewing, computer use and computer gaming (screen time) were consistently associated with back pain and recurrent headaches.

TorbjГёrn Torsheim, from the University of Bergen, Norway, worked with an international team of researchers to study the association between ‘screen time’ and head- or back-ache. He said, “A rising prevalence of physical complaints such as back pain, neck and shoulder pain, and headache has been reported for adolescent populations. Parallel to this, adolescents are spending an increasing amount of time on screen-based activities, such as TV, computer games, or other types of computer based entertainment”.

The researchers found that there was little interaction between specific types of screen-based activity and particular physical complaints, with the exception of headache in girls, which seemed to be particularly associated with computer use and TV viewing but not gaming. Torsheim and his colleagues suggest this indicates that physical complaints are not related to the type of screen-based activity, but to the duration and ergonomic aspects of such activity. Speaking about the findings, Torsheim said, “The consistent but relatively weak magnitude of associations is in line with the interpretation that screen time is a contributing factor, but not a primary causal factor, in headache and backache in the general population of Nordic school-aged teenagers.”

Notes:

Screen-based activities and physical complaints among adolescents from the Nordic countries
Torbjørn Torsheim, Lilly Eriksson, Christina W Schnohr, Fredrik Hansen, Thoroddur Bjarnason and Raili Välimaa
BMC Public Health (in press)

Source:
Graeme Baldwin

BioMed Central

Intense, short-term, upper-limb robotic therapy improved motor outcomes among chronic stroke patients. Investigators enrolled 30 patients with upper-limb impairment due to stroke. Over 3 weeks, 18 sessions of robot-assisted therapy were delivered with the use of a robotic exercise device. Significant improvements were observed for severely impaired participants, which indicates that improvement is not limited to individuals with moderate impairments. Moderately and severely impaired patients tolerated intense, frequent, and repetitive treatment. This information is useful for determining the optimal target population, intensity, and duration of robotic therapy and the necessary sample size for a larger trial.

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Highlight from JRRD pg. 717

Contact: Dr. Stacieann Yuhasz
yuhaszvard
VA Research Communications Service

Stroke patients improved functional use of their impaired arms and hands by participating in robotics plus motor learning or neuromuscular stimulation plus motor learning. Investigators randomly assigned patients with chronic stroke to one of two treatment groups: robotics with motor learning (ROB-ML) or functional neuromuscular stimulation with motor learning (FNS-ML). All participants received treatment 5 hours a day, 5 days a week for 12 weeks. Results showed that ROB-ML participants had gains in functional tasks, accuracy, and smoothness of movement. FNS-ML participants had gains in upper-limb coordination and hand/wrist function.

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Highlight from JRRD pg. 723

Contact: Dr. Stacieann Yuhasz
yuhaszvard
VA Research Communications Service