Possible Regeneration of Damaged Nerves

August 12, 2012 § Leave a comment

A serious injury can have lasting effects on victims of violent incidents such as car accidents, stabbings, and gunshot wounds, specifically in their nervous systems. Nerves and blood vessels can be split, bones can be broken, and cells can be damaged in such a way that, while wounds may heal and scars fade, the body never forgets.

 

The ruined debris from these injuries is often spread throughout the body like a wreckage site, making it extremely tricky to rectify. Highland Hospital neurosurgeon Jason Huang, M.D., who worked with Iraqi soldiers injured on the battlefield, is well aware that nerve damage is among the most difficult to treat.

Huang, now back at his University of Rochester Medical Center laboratory, is working with a team to increase the success of methods by which doctors can repair nerve damage. In the journal PLoS One, Huang and his colleagues published a report that there may be a specific group of cells useful in nerve transplantation.

Huang determines that, “Our long-term goal is to grow living nerves in the laboratory, then transplant them into patients and cut down the amount of time it takes for those nerves to work.” He explains that for a damaged nerve to repair itself, the two disengaged parts of the nerve must somehow reunite through a complicated labyrinth of tissues and cellular structures, then reconnect. For a small wound such as a scrape or a paper-cut, this occurs fairly easily, but for more destructive injuries, the nerve cannot repair itself without some kind of intercession.

Typically, the transplantation of nerve tissues from elsewhere in the patient’s body serves to scaffold for the repairs, like a rough sketch, that new nerves can fill in to bridge the gaps. The fact that these tissues come from the patient’s own body ensure that the immune system does not attack it.

Unfortunately in the case of severely injured patients, there is no healthy nerve tissue available from their own bodies. They must seek alternatives. Other options include nerve transplantation from human cadavers or animals, but this substitute involves lifelong dependency on extremely potent immunosuppressant drugs that come with a host of side effects.

The technology established by Huang and his team is called NeuraGen Nerve Guide. It includes a hollow, absorbable collagen tube that nerve fibers can grow and travel through to find each other. It is used to mend nerve damage over distances of less than half an inch long.

The team performed experiments on rats and found that dorsal root ganglion neurons (DRG cells) help to produce solid, healthy nerves, without inciting an undesirable reaction from the immune system. The team compared several methods to bridge half an inch nerve damage gaps in rats. They performed transplantations between rats combined with NeuraGen technology, comparing results of pairing NeuraGen with DRG cells, Schwann cells, and on its own. After four months, the tubes equipped with the DRG or Schwann cells were found to produce healthier nerves. Compared with each other, DRG cells incited the least amount of attention from the immune system, while Schwann cells attracted twice as many macrophages and more immune interferon gamma.

Schwann cells are currently more often preferred as potential partners in nerve transplantation, even though they cause problems due to the immune system’s reaction to them. Huang says, “The conventional wisdom has been that Schwann cells play a critical role in the regenerative process. While we know this is true, we have shown that DRG cells can play an important role also. We think DRG cells could be a rich resource for nerve regeneration.” This is great news for the yearly 350,000 patients in the United States who experience severe injuries to their peripheral nerves.

Huang’s laboratory is just one of many medical technology institutions geared towards the improvement of treatment methods for nerve damage. The team is currently collaborating with Douglas H. Smith’s team at the University of Pennsylvania to create DRG cells in the laboratory by stretching them. Stretching them encourages growth at the rate of one whole inch every three weeks. Instead of leaving it up to the nerves to travel and find each other inside the body, the team endeavors to grow the nerves externally in preparation for transplantation. This speeds the process of nerve repair.

 

Works Cited

“A Step Forward In Effort to Regenerate Damaged Nerves”. (February 21, 2012). Neuroscience News. March 2, 2012. http://neurosciencenews.com/regenerate-damaged-nerves-dorsal-root-ganglion/.

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Brain Cancer is Different in Children

August 12, 2012 § Leave a comment

Brain tumors are the chief cause of death for children with cancer in North America. Regardless of treatment, child Glioblastoma is a death sentence. Most children die within two years of diagnosis.

A study published the week of January 30th in the journal Nature reports that a major genetic breakthrough was made by an international research team, led by the Research Institute of the McGill University Health Centre (RI MUHC), which could possibly change the way pediatricians understand and treat child brain cancer.

Glioblastoma is a fatal brain cancer that is unresponsive to both chemotherapy and radiation therapy. The research team identified two genetic mutations that are responsible for up to 40% of Glioblastomas in children. The two mutations were discovered to be responsible for DNA regulation. Researchers suggest this may explain why Glioblastoma is resistant to traditional therapies.

Researchers from the team from McGill University and Génome Québec Innovation Centre identified the two mutations in the gene histone H3.3. The gene is very important, as it guards genetic heritage and is the key to modulating the expression of genes. The mutation apparently prevents cells from differentiating normally and helps to protect the genetic information of the cancerous cells.

The team’s head investigator Dr. Nada Jabado, a hematologist-oncologist at The Montreal Children’s Hospital of the McGill University Health Centre (MUHC), explains that this protective aspect makes it less sensitive to chemotherapy and radiotherapy. She says of previous child brain cancer research, “we’ve been failing to hit the right spot. … It is clear now that Glioblastoma in children is due to different molecular mechanisms than those in adults, and should not be treated in the same way.” She is optimistic about being able to know where to focus future efforts to treat the cancer.

Dr. Jabado also believes that this finding is only the beginning. Improper management of this gene, which protects genetic information, has also been observed in other cancers such as colon, pancreatic, lymphoma and leukemia. Future research could therefore uncover better treatments for these cancers as well. Dr. Jabado declares that, “This is the irrefutable proof that our genome, if modified, can lead to cancer and probably other diseases.”

Marc Le Page, President and CEO of Génome Québec, confirmed that, “The outstanding contribution of experts in genomics and new sequencing technologies, made by the McGill University and Génome Québec Innovation Centre and as part of Dr. Jabado’s project, is further proof that genomics has become essential for development and innovation in medical research.” Dr. Morag Park, Scientific Director of the CIHR Institute of Cancer Research, also congratulated Dr. Jabado and her team on the results of these findings, claiming that, “Through research advancements like this, there is now greater emphasis on using genetic information to make medical decisions.”

 

Works Cited

“Genetic Breakthrough for Brain Cancer in Children”. (January 30, 2012). Neuroscience News. February 18, 2012. http://neurosciencenews.com/genetic-breakthrough-brain-cancer-children-gene-brain-tumor/.

Alcohol-Induced Brain Shrinkage Linked to Genetic Vulnerability

August 7, 2012 § Leave a comment

A study to be published in the May 2012 issue of Alcoholism: Clinical and Experimental Research revealed that dopamine receptors DRD2 might perform a protective role against brain damage resulting from alcohol consumption. The study was conducted at the U.S. Department of Energy’s Brookhaven National Laboratory.

The research team issued significant volumes of alcohol to two different strains of mice. They then performed brain scans to observe for changes in brain size and functioning. The brain scans revealed significant shrinkage in certain critical brain regions in the mice that were lacking a certain dopamine receptor, DRD2. Dopamine is the brain’s “reward” chemical. This neurotransmitter is also responsible for the formation of new neurons in the adult brain.

This study explored how alcohol consumption affects brain volume in the two strains of mice. A control group was formed by splitting each strain of mice in half. Those in the control group were given plain water instead of alcohol. The two experimental groups were both given a 20% ethanol solution. After 6 months of this treatment, scientists performed MRI scans on all the mice and compared the four groups.

The scans revealed that consumption of alcohol generated considerable brain atrophy, with shrinkage occurring specifically in the cerebral cortex and thalamus of the mice that lacked the DRD2 receptors. In the mice with the normal receptor levels, significant shrinkage did not occur.

Study author, Foteini Delis, neuroanatomist at the Behavioral Neuropharmacology and Neuroimaging Lab at Brookhaven, said, “This study clearly demonstrates the interplay of genetic and environmental factors in determining the damaging effects of alcohol on the brain, and builds upon our previous findings suggesting a protective role of dopamine D2 receptors against alcohol’s addictive effects.” Coauthor Peter Thanos, neuroscientist at Brookhaven NIAAA, stated, “These studies should help us better understand the role of genetic variability in alcoholism and alcohol-induced brain damage in people, and point the way to more effective prevention and treatment strategies.”

Thanos claims that the use of mice as a model is valid because the same pattern of brain damage is found in the brain pathology of human alcoholics. In humans, these shrunken brain regions are responsible for processing speech, sensation, motor signals, and for the formation of long-term memory. Thanos says, “DRD2 may be protective against brain atrophy from chronic alcohol exposure … the findings imply that lower-than-normal levels of DRD2 may make individuals more vulnerable to the damaging effects of alcohol.” This means that those with low DRD2 levels are much more susceptible to the addictive and damaging effects of alcohol.

The findings of this study indicate that future research geared toward the understanding and treatment of alcoholism must target the dopamine system.

 

 

Works Cited

“Dopamine Controls Formation of New Brain Cells”. (April 8, 2011). Neuroscience News. February 19, 2012. http://neurosciencenews.com/dopamine-controls-formation-brain-cells-neurons/.

“Drinking Alcohol Shrinks Critical Brain Regions in Genetically Vulnerable Mice”. (February 15, 2012). Neuroscience News. February 19, 2012. http://neurosciencenews.com/drinking-alcohol-shrinks-brain-regions-genetics-mice-drd2/.

Molecules Developed for Treatment of Muscular Dystrophy

August 7, 2012 § Leave a comment

Scientists from the Florida campus of The Scripps Research Institute have published two findings in the online-before-print edition of Journal of the American Chemical Society and ACS Chemical Biology that are of great interest to those suffering from adult-onset muscular dystrophy. For the first time, researchers have developed a series of small molecules that act against the one RNA defect that is responsible for the most common form of the medical condition.

The small molecule compounds were found to drastically improve various biological defects associated with myotonic dystrophy type 1 (MD1) in both cell cultures and animal subjects. Matthew Disney, PhD, associate professor at Scripps Research Institute said, “Our compounds attack the root cause of the disease and they improve defects in animal models. This represents a significant advance in rational design of compounds targeting RNA. The work not only opens up potential therapies for this type of muscular dystrophy, but also paves the way for RNA-targeted therapeutics in general.”

MD1 is the result of an RNA defect called a “triplet repeat.” This is a sequence of three nucleotides, cytosine-uracil-guanine (CUG), in an individual’s genetic code that are repeated an abnormal and excess number of times. Repetition of these nucleotides in RNA initiates MD1 by binding to and deactivating MBNL1, a specific protein. The resulting abnormality is a continuous splicing of the proteins. This can affect the muscles, causing them to desecrate and waste away.

The researchers involved in the studies utilized data within the RNA motif-small molecule database that the group had been building to locate compounds that are hostile to the problem RNA implicated in the disease. They queried the database against the secondary structure of the triplet repeat that causes the disorder. The chief compound affecting this RNA was found with ease. Afterwards, these compounds were assembled in such a way as to target the increased repeat, or in some cases they were simply optimized. One of the compounds improved the protein-splicing defect by more than 40 percent in an animal subject.

As for the future of this research, Disney commented, “There are limitless RNA targets involved in disease; the question is how to find small molecules that bind to them. We’ve answered that question by rationally designing these compounds that target this RNA. There’s no reason that other bioactive small molecules targeting other RNAs couldn’t be developed using a similar approach.”

 

 

 

Works Cited

“Research Scientists Create Potent Molecules Aimed at Treating Muscular Dystrophy”. (February 22, 2010). Neuroscience News. March 2, 2012. http://neurosciencenews.com/myotonic-muscular-dystrophy-rna-targeted-therapy/.

Glioblastoma and Brain Cancer

August 7, 2012 § Leave a comment

Glioblastoma accounts for over half of all brain tumor cases where the tumor lies in the brain, as well as a fifth of cases in which a tumor exists within the skull. It is the most lethal, and therefore the most common, form of brain tumor in human beings.

Despite this fact, not many understand how Glioblastoma causes brain damage at the molecular level. Researchers at Vanderbilt University in Tennessee believe that a better understanding of the problems occurring at the molecular, genetic level might offer an understanding of the underlying mechanisms of carcinogenesis in the case of Glioblastoma, ultimately leading to possible treatments and preventative measures for the cancer.

Research published in the International Journal of Computational Biology and Drug Design offers a new way to understand the biological disordering that occurs when the tumor begins to form. The Vanderbilt team, lead by Zhongming Zhao, hypothesizes that the formulation of Glioblastoma may be due to the problems that occur during the protein-making genetic code transcription process. The problems might crop up due to actual changes in the genetic material itself, or alterations to the molecules involved in regulating the transcription process. Therefore in their recent research, the team has tested the possibility that microRNAs (miRNAs) and transcription factors (TFs) might be responsible for regulating the Glioblastoma genes.

Cancer can take many different forms. It is not a single disease but an array of complications. However, there are certain characteristics that allow us to identify the different forms, such as self-sufficiency in growth signals, insensitivity to antigrowth signals, evading programmed cell death, limitless replicative potential of cells, sustained blood-vessel growth, evasion of the immune system, tissue invasion and spreading through the body in metastasis. Understanding these molecular-level processes is crucial to their identification. This insight is now possible due to the creation of large catalogues of genomic and biochemical information related to the different types of cancer.

The Vanderbilt team researched three whole databases – miR2Disease, HMDD and PhenomiR – to find regulatory networks specific to Glioblastoma. To do this they combined data on Glioblastoma-related miRNAs, TFs and genes. They used TargetScan to search these databases and identified 54 so-called ‘feed-forward loops’ (FFLs). These are molecular control systems concerned with genetic code transcription and its required signaling processes. When follow-up work was performed, these FFLs were revealed to have essential roles in carcinogenesis.

The team concluded, “Our work provided data for future investigation of the mechanisms underlying Glioblastoma and also potential regulatory subunits that might be useful for biomarker discovery and therapy targets for Glioblastoma.”

 

Works Cited

“What Causes Brain Cancer? Understanding Glioblastoma”. (July 6, 2011). Neuroscience News. February 15, 2011. http://neurosciencenews.com/what-causes-brain-cancer-glioblastoma-genetics-microrna/

Early Signs of Autism

July 27, 2012 § Leave a comment

Researchers at the Washington University School of Medicine in St. Louis, the University of North Carolina at Chapel Hill, and others, have discovered a substantial disparity between the brain development of 6-month-old infants who later develop autism and infants who do not develop the disorder. The study embodies the latest findings from the Infant Brain Imaging Study Network, an initiative funded by the National Institutes of Health.

“We were surprised that there were so many differences so early in infancy,” said co-author Kelly N. Botteron, M.D., who is heading the endeavor at the Washington University site. The study in which these findings originated, published online in the American Journal of Psychiatry, involved infants with older siblings who had developed autism. These infants were considered high risk because the disorder was prevalent in their family.

The study involved nocturnal brain scans, which the researchers performed while the infants slept. 92 infants who had previously completed Diffusion Tensor Imaging (DTI) at 6 months of age were scanned. They were then given a behavioral assessment at 24 months of age. By the time the infants had reached 24 months, 30% of them were meeting criteria to place them in the autism spectrum. These findings suggest not only that autism develops over time, beginning in infancy, but also that the disorder may be detectable in infants as early as 6 months old.

Scans of the infants with autism uncovered evidence that there were changes in the pathways that connect brain regions to one another. There were significant changes to multiple fiber pathways in the brain’s white matter. Using DTI-assessed Fractional Anistropy (FA), which measures the regulation of white matter by observing the movement of water molecules through brain tissues, researchers analyzed 15 tracts of white matter and found significant differences in 12 tracts among the infants who later developed autism. These differences were not found in those infants who did not develop the disorder. “The idea that connections may be less organized in children with autism fits with our hypothesis,” says Gouttard S. Botteron, child psychiatrist at St. Louis Children’s Hospital.

He goes on to explain that the direction and rate of water movement is controlled by the surrounding structures. In the white matter tracts, the water has to flow in a particular direction to be parallel with the axons that connect different brain cells. “This highly constrained directional flow is characterized by higher FA,” he explains. This higher FA was found in 6-month-old infants who were later diagnosed with autism, but the FA values fell by the 24-month mark, indicating that these signs can only be detected early. Botteron expressed the team’s surprise at having found that almost every pathway examined showed these stark differences.

Jason J. Wolff, Ph.D., first author of the paper and a postdoctoral fellow at UNC’s Carolina Institute for Developmental Disabilities, says, “At this point, it’s a preliminary, albeit great, first step toward thinking about developing a biomarker for risk in advance of our current ability to diagnose autism.”

Researchers around North America are continuing Infant Brain Imaging Study on high-risk infants with funding from the National Institute of Child Health and Development of the National Institutes of Health, Autism Speaks, and the Simons Foundation.

 

 

Works Cited

Dryden, Jim. “Brain Differences Seen at 6 Months in Infants Who Develop Autism”. (February 17, 2012). Neuroscience News. February 18, 2012. http://neurosciencenews.com/brain-scans-6-months-infants-autism-diffusion-tensor-imaging-dti/.

Lithium Prevents Parkinson’s-Related Brain Damage

July 27, 2012 § Leave a comment

Parkinson’s disease is an incurable, progressive neurodegenerative disorder that affects 1 million Americans, and between 50,000 and 60,000 new cases are found annually. It is the second most common neurodegenerative disease after Alzheimer’s. It results in slowness of movement, rigidity, and tremors. PD is known to instigate cell loss, which often results in mild to acute brain damage.

Lithium has long been the gold standard for treatment of bipolar disorder. Now scientists at the Buck Institute for Research on Aging have discovered through rodent experimentation that Lithium also profoundly prevents the toxic protein aggregation that causes PD-related brain damage. Researchers at the Buck Institute are now ready to move into the preclinical stage to determine the correct dosages for the drug.

According to the June 24th edition of the Journal of Neuroscience Research, Buck researchers are working towards a Phase II human clinical study, using Lithium in concurrence with customary PD therapy. Lead author, Professor Julie Anderson, Ph.D., explains, “The fact that Lithium’s safety profile in humans is well understood greatly reduces trial risk.” Anderson explains that Lithium has significant anti-aging effects in animals. She mentions that, in contrast to the neurodegenerative properties of conditions such as Huntington’s disease, Alzheimer’s disease, and Amyotrophical Lateral Sclerosis, Lithium has recently been suggested to be neuroprotective.

Although overuse of Lithium has been known to cause hyperthyroidism and kidney toxicity, low dosages of the drug were given to the mice used in the Buck experimentation. Anderson remarks, “The possibility that Lithium could be effective in PD patients at subclinical levels is exciting, because it would avoid many side effects associated at the higher dose range.”

Although the Buck Institute’s research is still pre-clinical, success in previous experiments regarding the use of Lithium in humans is a predictor of future success in the case of patients with PD. In fact, research shows that many PD patients are already using Lithium, “off label,” in conjunction with their normal PD treatment regime. Also, Lithium salt supplements are available in some health food stores.

The familiarity of Lithium provides a better chance for the Buck Institute’s exploration with the drug. As Anderson explains, Lithium’s popularity, “lowers a significant hurdle to getting it into the clinic.”

 

 

Works Cited

“Lithium Profoundly Prevents Brain Damage Associated with Parkinson’s Disease”. (June 24, 2011). Neuroscience News. February 15, 2012. http://neurosciencenews.com/lithium-prevents-brain-damage-parkinsons-disease/.

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