Posts tagged science
Articles and news from the latest research reports.
Power of precision medicine in successful treatment of patient with disabling OCD
A multidisciplinary team led by a geneticist and psychiatrist from Cold Spring Harbor Laboratory’s (CSHL) Stanley Institute for Cognitive Genomics today publish a paper providing a glimpse of both the tremendous power and the current limitations of what is sometimes called “precision medicine.”
Precision medicine is an approach to diagnosis and treatment that tailors therapeutic care to individuals in a highly specific manner, and which brings to bear powerful new technologies that have not yet made it into the mainstream of clinical medicine, in part because they remain unproven.
Gholson J. Lyon, M.D., Ph.D., a CSHL researcher in molecular genetics and also a practicing psychiatrist, and collaborators at the University of Utah, the Utah Foundation for Biomedical Research (UFBR) and the companies Omicia, Inc. and AssureRx, report on their recruitment and treatment of a single patient with severe psychiatric illness. The man, identified as a 37-year-old U.S. military veteran, suffered from a form of obsessive-compulsive disorder (OCD) that rendered him completely disabled – profoundly compulsive and anxious, occasionally paranoid, and unable to hold a job or form meaningful relationships.
Over the past three years, the team successfully treated the man with an experimental form of electrical brain stimulation, called deep-brain stimulation (DBS). To date, DBS has been used most frequently to lessen symptoms in people with advanced Parkinson’s disease and also on an experimental basis to help lift otherwise untreatable, severe depression. Worldwide, only around 100 other people with OCD have been reported to have received DBS treatment on a trial basis. This was the first such instance, however, in which an individual with such severe mental illness, being treated with DBS, also consented to and received whole-genome sequencing, and rigorous post-sequencing analysis of the results, accompanied by genetic counseling.
Integrating the results
Each phase of the study generated significant data; but never had such data been integrated in the context of a single clinical psychiatric case. The results, which appear online today in the journal PeerJ, show that the patient was greatly helped by DBS. Over the treatment period, symptoms associated with OCD diminished to the point that the individual was able to “regain a quality of life that he had not previously experienced in over 15 years,” Dr. Lyon and colleagues report. As the electrical stimulation of his brain via DBS was optimized over time (this involved gradually increasing the voltage used in electrical stimulation), he was able to participate in regular exercise, work as a volunteer, and eventually meet someone and get married.
The researchers noted that several times during the treatment, when power from the battery that drives the DBS signals was either drained or not activated by the patient, symptoms of severe OCD returned over the course of 12-24 hours and rapidly became debilitating. This was both a powerful lesson to the patient to keep the device charged (the battery is rechargeable) and vivid evidence to the scientists regarding the device’s role in producing the patient’s observed symptomatic improvements.
Whole-genome sequencing, meantime, revealed that the patient carries at least three gene variants, or alleles, that have been associated in other studies with neuropsychiatric illness. These variants were in genes that encode proteins called BDNF, MTHFR and ChAT. The BDNF gene variant is of particular interest. Its protein is a prime growth factor essential in the early development and subsequent healthy function of the brain and nervous system. The other two variants have also been associated in past studies with possibly increasing the risks of mental illness.
Other gene variants were found that have implications for the way the patient is either able or unable to metabolize particular kinds of drugs. These and literally thousands of other bits of personal genomic information had no immediate impact on his treatment or prognosis, but were archived by Dr. Lyon’s team in the hope that at some later date they might be useful. One of the gene variants did prompt a referral for an eye exam, which revealed bilateral cataracts and poor night vision in this person, which the investigators are currently following up.
“Although we believe in archiving and managing all genetic results and not just a small subset of presently-known ‘risk genes,’ we did analyze the 57 genes in our subject’s genome that are currently recommended for ‘return of results’ to patients by the American College of Medical Genetics,” Dr. Lyon and the team notes.
“I met with this individual to go over the results with him” Dr. Lyon adds, “along with adding some of the findings into his paper-based medical record. We also contacted physicians and other officials at the US Veterans Administration office to offer to incorporate these data into the VA electronic medical record for this patient. We were told, however, that there is no current capacity at the VA to incorporate any genomic variant data.”
The inability even to enter the data in existing electronic health record databases points to the practical problems that remain in using comprehensive data sets to help evaluate and treat patients in a clinical context.
The team, however, believes its results demonstrate that “one can learn a substantial amount from detailed study of particular individuals,” and argues that “we are entering an era of precision medicine in which we can learn from and collect substantial data on informative individual cases.” They further note: “The genomic data we gathered would have been more helpful if obtained much earlier in the patient’s medical course, as it could have provided guidance on which medications to avoid or to provide in increased doses.”
Stem cells help repair traumatic brain injury by building a “biobridge”
University of South Florida researchers have suggested a new view of how stem cells may help repair the brain following trauma. In a series of preclinical experiments, they report that transplanted cells appear to build a “biobridge” that links an uninjured brain site where new neural stem cells are born with the damaged region of the brain.
Their findings were recently reported online in the peer-reviewed journal PLOS ONE.
“The transplanted stem cells serve as migratory cues for the brain’s own neurogenic cells, guiding the exodus of these newly formed host cells from their neurogenic niche towards the injured brain tissue,” said principal investigator Cesar Borlongan, PhD, professor and director of the USF Center for Aging and Brain Repair.
Based in part on the data reported by the USF researchers in this preclinical study, the U.S. Food and Drug Administration recently approved a limited clinical trial to transplant SanBio Inc’s SB632 cells (an adult stem cell therapy) in patients with traumatic brain injury.
Stem cells are undifferentiated, or blank, cells with the potential to give rise to many different cell types that carry out different functions. While the stem cells in adult bone marrow or umbilical cord blood tend to develop into the cells that make up the organ system from which they originated, these multipotent stem cells can be manipulated to take on the characteristics of neural cells.
To date, there have been two widely-held views on how stem cells may work to provide potential treatments for brain damage caused by injury or neurodegenerative disorders. One school of thought is that stem cells implanted into the brain directly replace dead or dying cells. The other, more recent view is that transplanted stem cells secrete growth factors that indirectly rescue the injured tissue.
The USF study presents evidence for a third concept of stem-cell mediated brain repair.
The researchers randomly assigned rats with traumatic brain injury and confirmed neurological impairment to one of two groups. One group received transplants of bone marrow-derived stem cells (SB632 cells) into the region of the brain affected by traumatic injury. The other (control group) received a sham procedure in which solution alone was infused into the brain with no implantation of stem cells.
At one and three months post-TBI, the rats receiving stem cell transplants showed significantly better motor and neurological function and reduced brain tissue damage compared to rats receiving no stem cells. These robust improvements were observed even though survival of the transplanted cells was modest and diminished over time.
The researchers then conducted a series of experiments to examine the host brain tissue.
At three months post-traumatic brain injury, the brains of transplanted rats showed massive cell proliferation and differentiation of stem cells into neuron-like cells in the area of injury, the researchers found. This was accompanied by a solid stream of stem cells migrating from the brain’s uninjured subventricular zone — a region where many new stem cells are formed – to the brain’s site of injury.
In contrast, the rats receiving solution alone showed limited proliferation and neural-commitment of stem cells, with only scattered migration to the site of brain injury and virtually no expression of newly formed cells in the subventricular zone. Without the addition of transplanted stem cells, the brain’s self-repair process appeared insufficient to mount a defense against the cascade of traumatic brain injury-induced cell death.
The researchers conclude that the transplanted stem cells create a neurovascular matrix that bridges the long-distance gap between the region in the brain where host neural stem cells arise and the site of injury. This pathway, or “biobridge,” ferries the newly emerging host cells to the specific place in the brain in need of repair, helping promote functional recovery from traumatic brain injury.
Cell auto-cleaning mechanism mediates the formation of plaques in Alzheimer’s
Autophagy, a key cellular auto-cleaning mechanism, mediates the formation of amyloid beta plaques, one of the hallmarks of Alzheimer’s disease. It might be a potential drug target for the treatment of the disease, concludes new research from the RIKEN Brain Science Institute in Japan. The study sheds light on the metabolism of amyloid beta, and its role in neurodegeneration and memory loss.
In a study published today in the journal Cell Reports, Drs. Per Nilsson, Takaomi Saido and their team show for the first time using transgenic mice that a lack of autophagy in neurons prevents the secretion of amyloid beta and the formation of amyloid beta plaques in the brain. The study also reveals that an accumulation of amyloid beta inside neurons is toxic for the cells.
Alzheimer’s disease, the most common form of dementia, affects nearly 36 million people worldwide, and this number is set to double over the next 20 years. However, the causes of the disease are not well understood and no disease-modifying treatment is available today.
Patients with Alzheimer’s disease have elevated levels of the peptide amyloid beta in their brain and amyloid beta plaques form outside their neurons. This accumulation of amyloid beta causes the neurons to die, but until now the underlying mechanism remained a mystery. And whether the elevated levels of the peptide inside or outside the cells are to blame was unknown.
Autophagy is a cellular cleaning mechanism that normally clears any protein aggregates or other ‘trash’ within the cells, but that is somewhat disturbed in Alzheimer’s patients.
To investigate the role of autophagy in amyloid beta metabolism, Nilsson et al. deleted an important gene for autophagy, Atg7, in a mouse model of Alzheimer’s disease. Contrary to what they were expecting, their results showed that a complete lack of autophagy within neurons prevents the formation of amyloid beta plaque around/outside the cells. Instead, the peptide accumulates inside the neurons, where it causes neuronal death, which in turn leads to memory loss.
“Our study explains how amyloid beta is secreted from the neurons, via autophagy, which wasn’t well understood,” comments Dr Nilsson. “To control amyloid beta metabolism including its secretion is a key to control the disease. Autophagy might therefore be a potential drug target for the treatment of Alzheimer’s disease,” he adds.
Blocking nerve cells could halt symptoms of eczema
Some 10 percent of the population suffers from eczema at some point in their lives. The chronic skin condition, for which there are no cures or good treatments, causes symptoms ranging from dry, flaky and itchy skin to flaming red rashes and, particularly in children, nasal allergies and asthma.
Scientists at the University of California, Berkeley, have developed a new picture of how the nervous system interacts with the immune system to cause the itch and inflammation associated with eczema. Their findings could lead to new therapies for the disease.
Eczema’s cause is unknown, but most research today focuses on the immune system’s role in reacting to chemicals that cause itching and inflammation. UC Berkeley neuroscientist Diana M. Bautista and graduate students Sarah R. Wilson and Lydia Thé, however, discovered that sensory nerves in the skin are the first to react to these chemicals, and that blocking the skin’s itch receptors not only stops the scratching, but may head off the worst consequences of eczema.
“Most drug development has focused on trying to find a way to inhibit the immune response,” said Bautista, assistant professor of molecular and cell biology and a member of the Helen Wills Neuroscience Institute. “Now that we have found that sensory neurons may be the first responders, that changes how we think about the disease.”
“By just blocking what is happening in the neurons, you could block the symptoms of chronic itch, including the big immune response leading to asthma and allergy,” Wilson added. “And you prevent the patient from scratching, which damages skin cells and makes them release more chemicals that cause inflammation and help maintain chronic itch.”
The researchers already have identified a potential drug, now in Phase 1 clinical trials for a different inflammatory disease, that stops mice from scratching when it is applied to the skin.
Their new model of eczema is based on findings reported online today (Thursday, Oct. 3) in the journal Cell by Bautista, Wilson, Thé and their UC Berkeley colleagues.
Block that wasabi
“We started out looking at acute itch and asked the question, ‘Why do we scratch? Why do we have that urge, and how does it work that scratching gives you some relief, when normally it feels terrible if you don’t have an itch and scratch yourself that hard?’” Bautista said. “But the many types of chronic itch that humans experience are all very different. We believe that, through identifying molecular mechanisms, we can find new treatments and therapies for these diseases.”
Immunologists several years ago identified a chemical – TSLP (thymic stromal lymphopoietin), a so-called cytokine – that induces itch when expressed in the skin. Because immune cells have receptors for this chemical, TSLP triggers them to release chemicals that attract other immune cells and to create the red, itchy inflammation typical of eczema. These inflammatory chemicals seem to spread through the body and induce inflammation in the lungs, gut and nasal passages that lead to asthma and allergies, Bautista said.
Wilson and Bautista, however, focused on what causes the immediate or acute itch. Probing itch-sensitive neurons in the skin, they found that these neurons also have receptors for TSLP, and that TSLP makes these neurons, like immune cells, release chemical mediators that cause inflammation. Furthermore, by looking at human skin cells (keratinocytes) in culture, they discovered the triggers that make skin cells release TSLP in the first place.
“Our hypothesis is that skin cells release TSLP, which triggers neurons to release mediators that lead to more inflammation and recruitment of immune cells,” helping to set up chronic inflammation, Bautista said.
“These itch-sensitive neurons are a small population,” she added. “If we could just block the 2 percent of neurons that respond to TSLP, we could have a really selective drug that treats chronic itch, but keeps all of the important functions of skin – normal pain function, normal temperature and tactile sensations – and the many parts of the immune system intact.”
Interestingly, the TSLP receptor works through an ion channel, TRPA1, that Bautista discovered when she was a post-doctoral researcher. The channel was named the wasabi ion channel because it is sensitive to “mustard compounds” like those found in Dijon or wasabi. Blockers of the wasabi channel thus would block the action of TSLP and stop itch.
Alternatively, Wilson said, drug developers could look for chemicals that block the release of TSLP from damaged skin cells.
Bautista and her colleagues are continuing to explore the relative contributions of different types of nerve and immune cells to atopic dermatitis and chronic itch and are developing mouse models in which to test their hypotheses.
Did you have a good time? We know where you’ll store the memory of it!
Where do you go for a tasty bite and where the food is not so good? Where are you likely to meet an attractive partner and where you risk damage to your health? For every person – but also for animals – the information about pleasant and unpleasant experiences is of key importance. Researchers from the Nencki Institute in Warsaw discovered how and where nice memories are stored.
As shown by researchers from the Nencki Institute of Experimental Biology in Warsaw, Poland, nice memories are stored in an area of the brain known as the central nucleus of the amygdala. The results obtained by the group of Prof. Leszek Kaczmarek and Dr. Ewelina Knapska, which were published in the well-known Journal of Neuroscience show that just one protein plays the key role in the process of memorizing pleasant experiences. In the future these results may help design more effective treatment of addictions, depression and schizophrenia.
“We want our research to help us understand the relation between the mind and the brain by studying memory, which is of fundamental importance for the mind. Without memory there is no mind”, Prof. Kaczmarek explains context of the research.
Neurobiologists differentiate between many types of memory, the most basic types of which are characterized by clear duality. For example we have short and long term memories, declarative (referring to events/data) and procedural (memory of actions). Researchers from the Nencki Institute focused on another dichotomy of great importance to every animal. They focused on appetitive memory related to memories of pleasant experiences and aversive memory related to unpleasant experiences.
Experimental research on human memory often comes across a very basic problem: there are no volunteers for the experiments. No one of sound mind will agree to participate in experiments involving his or her own memory. Fortunately having a mind is not limited to humans. Many mental activities typical for humans take place also in the minds of animals. Therefore scientists from the Nencki Institute conducted their experiments on mice.
These novel experiments on memory have been conducted on mice placed in the so-called IntelliCages. In each corner of such cage two water bottles have been placed. In order to get water a mouse has to get to the corner and nose poke on a small gate of a given bottle. Depending on the type of experiment, the mouse will either get water or harmless but unpleasant puff of air on the nose. All mice in the cage have individual ID chips and therefore researchers are able to tell exactly what decisions are made by each mouse.
IntelliCages make it possible to conduct different experiments. If for example in one corner sweet water (that is an appetitive stimulus) bottles are placed, the effectiveness of spatial memory in mice can be investigated. More subtle experiments are also possible by placing only one sweet water bottle in a selected corner. Then the mouse needs to remember not only the corner where the sweet water bottle is, but also which of two bottles contains sweet water.
Twenty five years ago Nencki researchers have observed changes in the activity of a gene known as c-fos in the nervous cell nuclei during learning. One of the proteins, the production of which is regulated by a protein encoded by the c-fos gene, is the MMP-9 enzyme active outside of the cell. Researchers decided to investigate the role of MMP-9 in memorizing pleasant and unpleasant experiences. In order to do this a series of experiments was conducted on control mice and on mice either lacking this protein entirely or with its selective blocking only within the central amygdala.
The amygdala is a small structure within the cerebral hemisphere and it is located at the base of the brain, close to the hippocampus. It consists of two groups of nuclei responsible for innate and acquired emotional reactions, such as laughter or fear.
Researchers were surprised by the experiments. When placed in the IntelliCages, the control mice after three days of learning almost always chose the corner with sweet water. Mice lacking MMP-9 behaved distinctly different: they showed no preference for any of the corners. At the same time all mice equally well remembered the corner where they received the unpleasant puff on their noses. Furthermore, selective blocking of MMP-9 just in the central amygdala produced the same effect – the memory for the sweet water location could not be formed.
“The results are clear. Pleasant experiences are memorised due to changes in plasticity within the neurons of the central nucleus of the amygdala. At the same time we have shown that just one protein, the MMP-9, is responsible for learning about pleasant experiences themselves and memorizing them. At the same time this protein has no impact on the memory of unpleasant experiences. These are important discoveries and to tell the truth making them was… very pleasant”, says Prof. Kaczmarek.
These research results, which stem from experiments conducted at the Nencki Institute for the past 25 years, hold great scientific significance for they explain the processes of learning and appetitive memory by referring to two seemingly very distant domains of neurobiology: system – investigating entire neuronal structures (such as the central nucleus of the amygdala) – and molecular, investigating physical and chemical processes responsible for various functions of nervous cells (in which the MMP-9 protein takes part).
Scientists Develop New Process to Create Artificial Cell Membranes
The membranes surrounding and inside cells are involved in every aspect of biological function. They separate the cell’s various metabolic functions, compartmentalize the genetic material, and drive evolution by separating a cell’s biochemical activities. They are also the largest and most complex structures that cells synthesize.
Understanding the myriad biochemical roles of membranes requires the ability to prepare synthetic versions of these complex multi-layered structures, which has been a long-standing challenge.
In a study published this week by Nature Chemistry, scientists at The Scripps Research Institute (TSRI) report a highly programmable and controlled platform for preparing and experimentally probing synthetic cellular structures.
“Layer-by-layer membrane assembly allows us to create synthetic cells with membranes of arbitrary complexity at the molecular and supramolecular scale,” said TSRI Assistant Professor Brian Paegel, who authored the study with Research Associate Sandro Matosevic. “We can now control the molecular composition of the inner and outer layers of a bilayer membrane, and even assemble multi-layered membranes that resemble the envelope of the cell nucleus.”
Starting with a technique commonly used to deposit molecules on a solid surface, Langmuir-Blodgett deposition, the scientists repurposed the approach to work on liquid objects.
The scientists engineered a microfluidic device containing an array of microscopic cups, each trapping a single droplet of water bathed in oil and lipids, the molecules that make up cellular membranes. The trapped droplets are then ready to serve as a foundation for building up a series of lipid layers like coats of paint.
The lipid-coated water droplets are first bathed in water. As the water/oil interface encounters the trapped droplets, a second lipid layer coats the droplets and transforms them into what are known as unilamellar or single-layer vesicles. Bathing the vesicles in oil/lipid deposits a third lipid layer, and followed by a final layer of lipids that is deposited on the trapped drops to yield double-bilayer vesicles.
“The computer-controlled microfluidic circuits we have constructed will allow us to assemble synthetic cells not only from biologically derived lipids, but from any amphiphile and to measure important chemical and physical parameters, such as permeability and stability,” said Paegel.
(Source: scripps.edu)
Researchers identify the neural circuits that modulate REM sleep
A team of scientists led by Dr. Antoine Adamantidis, a researcher at the Douglas Mental Health University Institute and an assistant professor at McGill University, has released the findings from their latest study, which will appear in the October issue of the prestigious scientific journal Nature Neuroscience.
(Image: iStockphoto)
Previous studies had established an association between the activity of certain types of neurons and the phase of sleep known as REM (rapid eye movement). Researchers on the team of Dr. Antoine Adamantidis identified, for the first time, a precise causal link between neuronal activity in the lateral hypothalamus (LH) and the state of REM sleep. Using optogenetics, they were able to induce REM sleep in mice and modulate the duration of this sleep phase by activating the neuronal network in this area of the brain.
This achievement is an important contribution to the understanding of sleep mechanisms in the brains of mammals, as well as the underlying neuronal network, which is still not well understood despite recent breakthroughs in neuroscience.
Better understanding how sleep is modulated to reduce sleep disorders
“These research findings could help us better grasp how the brain controls sleep and better understand the role of sleep in humans. These results could also lead to new therapeutic strategies to treat sleep disorders along with associated neuropsychiatric problems,” stated Dr. Antoine Adamantidis, who is also the Canada Research Chair in Neural Circuits and Optogenetics.
What is REM (rapid eye movement) sleep?
There are two types of sleep: REM and non-REM sleep. In humans, non-REM sleep has four stages. REM sleep, or deep sleep, is generally associated with dreaming and is a phase when the brain is very active, even though people are in a heavy sleep, their eyes move rapidly (hence the name), and their bodies have an almost total loss of muscle tonus.
Although our understanding of the mechanisms that control the wake and sleep cycle has progressed in recent years, many frontiers remain unexplored. However, we do know that a disruption in sleep can lead to adverse effects on physical and mental health in humans.
Optogenetics, a revolutionary technology
In 2010 in the journal Nature, optogenetics was recognized as one of the coming decade’s most promising techniques to better understand brain function. This new field of research and application integrates optics and genetics methodologies to modulate the activity of neural circuits. Optogenetics involves controlling neuronal activity with light. This technique is therefore used to manipulate a specific type of cell without affecting neighbouring cells. A researcher who uses optogenetics is therefore like a conductor who decides to change the sheet music for an instrument to observe the effects, however insignificant they may seem, on the orchestra’s entire performance.
(Source: douglas.qc.ca)
Decoding Sounds’ Source: Researchers Unravel Part of Mystery
As Baby Boomers age, many experience difficulty in hearing and understanding conversations in noisy environments such as restaurants. People who are hearing-impaired and who wear hearing aids or cochlear implants are even more severely impacted. Researchers know that the ability to locate the source of a sound with ease is vital to hear well in these types of situations, but much more information is needed to understand how hearing works to be able to design devices that work better in noisy environment.
Researchers from the Eaton-Peabody Laboratories of the Massachusetts Eye and Ear, Harvard Medical School, and Research Laboratory of Electronics, Massachusetts Institute of Technology have gained new insight into how localized hearing works in the brain. Their research is published in the Oct. 2, 2013 issue of the Journal of Neuroscience.
“Most people are able to locate the source of a sound with ease, for example, a snapping twig on the left, or a honking horn on the right. However this is actually a difficult problem for the brain to solve,” said Mitchell L. Day, Ph.D., investigator in the Eaton-Peabody Laboratories at Mass. Eye and Ear and instructor of Otology and Laryngology at Harvard Medical School “The higher levels of the brain that decide the direction a sound is coming from do not have access to the actual sound, but only the representation of that sound in the electrical activity of neurons at lower levels in the brain. How higher levels of the brain use information contained in the electrical activity of these lower-level neurons to create the perception of sound location is not known.”
In the experiment, researchers recorded the electrical activity of individual neurons in an essential lower-level auditory brain area called the inferior colliculus (IC) while an animal listened to sounds coming from different directions. They found that the location of a sound source could be accurately predicted from the pattern of activation across a population of less than 100 IC neurons – i.e., a particular pattern of IC activation indicated a particular location in space. Researchers further found that the pattern of IC activation could correctly distinguish whether there was a single sound source present or two sources coming from different directions – i.e., the pattern of IC activation could segregate concurrent sources.
“Our results show that higher levels of the brain may be able to accurately segregate and localize sound sources based on the detection of patterns in a relatively small population of IC neurons,” said Dr. Day. “We hope to learn more so that someday we can design devices that work better in noisy environments.”
(Source: masseyeandear.org)
Tests In Mice Identify Compound That May Keep Survivors of Ruptured Brain Aneurysms From Later Succumbing to Stroke
Johns Hopkins researchers, working with mice, say they have identified a chemical compound that reduces the risk of dangerous, potentially stroke-causing blood vessel spasms that often occur after the rupture of a bulging vessel in the brain.
They say their findings offer clues about the biological mechanisms that cause vasospasm, or constriction of blood vessels that reduces oxygen flow to the brain, as well as potential means of treating the serious condition in humans.
When an aneurysm — essentially a blister-like bulge in the wall of a blood vessel — bursts, blood spills into the fluid-filled space that cushions the brain inside the skull. If a patient survives a ruptured aneurysm, between 20 and 40 percent of the time, this brain bleed, called a subarachnoid hemorrhage, will lead to an ischemic stroke within four to 21 days, even when the aneurysm is surgically clipped.
“We’re a long way from applying this to humans, but it’s a good start,” says Johns Hopkins neurosurgery resident Tomas Garzon-Muvdi, M.D., M.Sc., one of the authors of the study led by Rafael J. Tamargo, M.D., and described in the October issue of the journal Neurosurgery.
To conduct their experiments, Garzon-Muvdi and his colleagues took blood from mouse leg arteries and injected it behind their necks to mimic what happens in a subarachnoid hemorrhage. Then they gave the mice a compound called (S)-4-carboxyphenylglycine (S-4-CPG), a placebo or nothing at all. The mice given S-4-CPG developed less vasospasm, looked better and were more active than those in the other two groups.
The scientists also found concentrations of the drug in the brains of the mice, showing that it was able to cross the often impermeable blood-brain barrier. The researchers chose the compound because it is similar to drugs that have been used in stroke research in rodents. It is not approved for any use in humans.
Garzon-Muvdi explains that when blood vessels break anywhere but the brain, the body’s immune cells easily clear the blood cells and their remnants from the area. This is what happens with a bruise, when immune cells rush to the area, and a chemical cascade scavenges and disperses the remnants of excess blood components.
When a blood vessel bursts in the space around the brain, however, the blood is trapped. A subsequent inflammatory response brings key immune system cells into the space, where they secrete the neurotransmitter glutamate outside of the blood vessels where it shouldn’t be, promoting dangerous vasospasm in those blood vessels. This can lead to ischemic stroke, the most common type of stroke, caused by a blockage of a blood vessel in the brain. Death or serious disability may result.
The Johns Hopkins researchers say S-4-CPG keeps glutamate “in check,” prevents or reduces vasospasm and allows oxygen-filled blood to continue flowing into the brain.
According to the National Institutes of Health, subarachnoid hemorrhage caused by a cerebral aneurysm that breaks open occurs in about 40 to 50 out of 100,000 people over age 30. Patients may die immediately, but those who survive are still at elevated risk for developing an ischemic stroke in the days afterward. These patients are often watched very carefully in the intensive care unit for one to two weeks to search for early signs of vasospasm so that doctors can take steps to prevent or limit damage from a stroke.
In the ICU, doctors can order regular angiograms or ultrasounds to measure blood flow in vessels. If need be, they can increase blood pressure to send blood through vessels faster in the hopes of counteracting the constriction.
A drug to prevent stroke after a serious subarachnoid hemorrhage that follows the rupture of an aneurysm would improve quality of life for patients, Garzon-Muvdi says, and could potentially save millions of dollars in health care costs if patients don’t have to endure extensive hospital stays to monitor for a delayed stroke.
(Source: hopkinsmedicine.org)
Small brain biopsies can be used to grow large numbers of patient’s own brain cells
A group of really brainy scientists have moved closer to growing “therapeutic” brain cells in the laboratory that can be re-integrated back into patients’ brains to treat a wide range of neurological conditions. According to new research published online in The FASEB Journal, brain cells from a small biopsy can be used to grow large numbers of new personalized cells that are not only “healthy,” but also possess powerful attributes to preserve and protect the brain from future injury, toxins and diseases. Scientists are hopeful that ultimately these cells could be transformed in the laboratory to yield specific cell types needed for a particular treatment, or to cross the “blood-brain barrier” by expressing specific therapeutic agents that are released directly into the brain.
"This work is an example of how integrating basic science and clinical care may reveal privileged opportunities for biomedical research," said Matthew O. Hebb, M.D., Ph.D., FRCSC, a researcher involved in the work from the Departments of Clinical Neurological Sciences (Neurosurgery), Oncology and Otolaryngology at the University of Western Ontario in Ontario, Canada. "It is our hope that the results of this study provide a footing for further advancement of personalized, cell-based treatments for currently incurable and devastating neurological disorders."
Scientists enrolled patients with Parkinson’s disease who were scheduled to have deep brain stimulation (DBS) surgery, a commonly used procedure that involves placing electrodes into the brain. Before the electrodes were implanted, small biopsies were removed near the surface of the brain and multiplied in culture to generate millions of patient-specific cells that were then subjected to genetic analysis. These cells were complex in their make-up, but exhibited regeneration and characteristics of a fundamental class of brain cells, called glia. They expressed a broad array of natural and potent protective agents, called neurotrophic factors.
"From an extremely small amount of brain tissue, we will one day be able to do very big things," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “For centuries, treating the brain effectively and safely has been elusive. This advance opens the doors to not only new therapies for a myriad of brain diseases, but new ways of delivering therapies as well.”
(Source: eurekalert.org)