TAG: "brain"

Colds may temporarily increase stroke risk in kids


Study shows colds, flu can create short-lived increased stroke risk in vulnerable children.

A new study suggests that colds and other minor infections may temporarily increase stroke risk in children. The study found that the risk of stroke was increased only within a three-day period between a child’s visit to the doctor for signs of infection and having the stroke.

The study was led by researchers at UCSF Benioff Children’s Hospital San Francisco in collaboration with the Kaiser Permanente Division of Research.

“These findings suggest that infection has a powerful but short-lived effect on stroke risk,” said senior author Heather Fullerton, M.D., a pediatric vascular neurologist and medical director of the Pediatric Brain Center at UCSF Benioff Children’s Hospital San Francisco.

“We’ve seen this increase in stroke risk from infection in adults, but until now, an association has not been studied in children.”

Strokes are extremely rare in children, affecting just 5 out of 100,000 kids per year. “The infections are acting as a trigger in children who are likely predisposed to stroke,” said Fullerton. “Infection prevention is key for kids who are at risk for stroke, and we should make sure those kids are getting vaccinated against whatever infections – such as flu – that they can.”

The study appears in today’s (Aug. 20) online issue of Neurology.

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UC scientists awarded 8 grants in support of BRAIN Initiative


Projects seek to gain understanding of the brain.

Eight University of California scientists are among 36 recipients nationwide who have been awarded early concept grants for brain research from the National Science Foundation, the agency announced today (Aug. 18).

The awards were made to fund research projects that the federal science agency determined could produce “potentially transformative insights into understanding the brain.” The funding comes from the agency’s allocation for President Obama’s BRAIN Initiative, a multi-agency research effort that seeks to accelerate the development of new neurotechnologies that promise to help researchers answer fundamental questions about how the brain works.

The NSF’s 36 early concept grant awards, which total $10.8 million, are intended to “enable new technologies to better understand how complex behaviors emerge from the activity of brain circuits,” the agency said.

Each of these Early Concept Grants for Exploratory Research, or EAGER, awards will receive $300,000 over a two-year period to “develop a range of conceptual and physical tools, from real-time whole brain imaging, to new theories of neural networks, to next-generation optogenetics,” the NSF said.

UC scientists played a major role in the creation of Obama’s BRAIN initiative in April 2013 and also led a similar state initiative that, two months ago, was awarded $2 million in the budget signed into law by Gov. Jerry Brown. The state’s research grant effort, known as Cal-BRAIN – short for California Blueprint for Research to Advance Innovations in Neuroscience – aims to “accelerate the development of brain mapping techniques, including the development of new technologies.”

“These awards are yet another manifestation of the excellence of our neuroscience faculty and our long tradition in neuroscience research, which were key factors in building the number one ranked neuroscience graduate program in the nation and establishing our Kavli Institute for Brain and Mind,” said UC San Diego Chancellor Pradeep K. Khosla.

UC early concept grant awardees include:

UC Berkeley
Ehud Isacoff

UC Davis
Martin Usrey
Karen Zito

UC San Diego
Brenda Bloodgood
Andrea Chiba
David Kleinfeld
Charles Stevens

UC San Francisco
Steven Finkbeiner

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Mapping the infant brain


Findings may be key in identifying, treating earliest signs of neurodevelopmental disorders.

A recent study conducted by researchers at the UC San Diego School of Medicine and the University of Hawaii demonstrates a new approach to measuring early brain development of infants, resulting in more accurate whole brain growth charts and providing the first estimates for growth trajectories of subcortical areas during the first three months after birth. Assessing the size, asymmetry and rate of growth of different brain regions could be key in detecting and treating the earliest signs of neurodevelopmental disorders, such as autism or perinatal brain injury.

The study will be published in JAMA Neurology today (Aug. 11).

For the first time, researchers used magnetic resonance imaging (MRI) of the newborn brain to calculate the volume of multiple brain regions and to map out regional growth trajectories during the infant’s first 90 days of life. The study followed the brain growth of full term and premature babies with no neurological or major health issues.

“A better understanding of when and how neurodevelopmental disorders arise in the postnatal period may help assist in therapeutic development, while being able to quantify related changes in structure size would likely facilitate monitoring response to therapeutic intervention. Early intervention during a period of high neuroplasticity could mitigate the severity of the disorders in later years,” said Dominic Holland, Ph.D., first author of the study and researcher in the Department of Neurosciences at UC San Diego School of Medicine.

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Single-cell analysis holds promise for stem cell, cancer research


UCSF researchers use microfluidic technology to probe human brain development.

Arnold Kriegstein, UC San Francisco

UC San Francisco researchers have identified cells’ unique features within the developing human brain, using the latest technologies for analyzing gene activity in individual cells, and have demonstrated that large-scale cell surveys can be done much more efficiently and cheaply than was previously thought possible.

“We have identified novel molecular features in diverse cell types using a new strategy of analyzing hundreds of cells individually,” said Arnold Kriegstein, M.D., Ph.D., director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. “We expect to use this approach to help us better understand how the complexity of the human cortex arises from cells that are spun off through cell division from stem cells in the germinal region of the brain.”

The research team used technology focused on a “microfluidic” device in which individual cells are captured and flow into nanoscale chambers, where they efficiently and accurately undergo the chemical reactions needed for DNA sequencing. The research showed that the number of reading steps needed to identify and spell out unique sequences and to successfully identify cell types is 100 times fewer than had previously been assumed. The technology, developed by Fluidigm Corp., can be used to individually process 96 cells simultaneously.

“The routine capture of single cells and accurate sampling of their molecular features now is possible,” said Alex Pollen, Ph.D., who along with fellow Kriegstein-lab postdoctoral fellow Tomasz Nowakowski, Ph.D., conducted the key experiments, in which they analyzed the activation of genes in 301 cells from across the developing human brain. Their results were published online August 3 in Nature Biotechnology.

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Gaining insights into the nervous system


Rita Allen Foundation Scholarship supports brain imaging studies.

Neuron picture: synaptic terminal of cortical layer2/3 neurons labeled with targeted genetically encoded sensors of neural activity.

Lin Tian’s fascination with neuroscience stems from a deep curiosity about the complexity and elegance of the human brain. As one of only five scientists in the U.S. and Canada — and the first at UC Davis — to be named a 2014 Rita Allen Foundation Scholar, Tian will be developing optical sensors and applications to acquire fundamental insights about how the nervous system functions in health and disease.

“The functioning brain receives thousands of chemical and electrical signals at the synapse, the area of connection between neurons,” Tian said. “Understanding how neurons integrate these multiple inputs to transmit information and to shape and refine the neural circuitry itself is an important area of research that can shed light on an array of neurological disorders, including depression, addiction, autism, schizophrenia and epilepsy.”

With a five-year, $500,000 grant from the Rita Allen Foundation, Tian will develop imaging tools to obtain a comprehensive view of both excitatory and inhibitory synapses in action at the cellular, tissue and whole-animal levels. She also will apply these tools to uncover the functional organization of cortical layer1 (L1) interneurons in shaping long-range interactions and their link to behavior, which can’t be done with current technology, Tian said.

“Understanding how information is transferred across neural circuitry and systems is the key to innovation in the treatment of neurological disorders,” she said.

Tian is an assistant professor of biochemistry and molecular medicine at UC Davis. She holds a bachelor’s degree in neuroscience from the University of Science and Technology of China and a doctorate in biochemistry, molecular and cell biology from Northwestern University. She completed her postdoctoral training at Howard Hughes Medical Institute Janelia Farm.

Since 1976, more than one hundred young leaders in biomedical science have been selected as Rita Allen Foundation Scholars. The program embraces innovative research with above-average risk and promise. Scholars have gone on to win the Nobel Prize in Physiology or Medicine, the National Medal of Science, the Wolf Prize in Medicine, and the Breakthrough Prize in Life Sciences.

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Kids with autism, SPD show brain wiring differences


UCSF study builds on its research showing kids with SPD have measurable brain differences.

Pratik Mukherjee, UC San Francisco

Researchers at UC San Francisco have found that children with sensory processing disorders have decreased structural brain connections in specific sensory regions different than those in autism, further establishing SPD as a clinically important neurodevelopmental disorder.

The research, published in the journal PLOS ONE, is the first study to compare structural connectivity in the brains of children with an autism diagnosis versus those with an SPD diagnosis, and with a group of typically developing boys. This new research follows UCSF’s groundbreaking study published in 2013 that was the first to find that boys affected with SPD have quantifiable regional differences in brain structure when compared to typically developing boys. This work showed a biological basis for the disease but prompted the question of how these differences compared with other neurodevelopmental disorders.

“With more than 1 percent of children in the U.S. diagnosed with an autism spectrum disorder, and reports of 5 to 16 percent of children having sensory processing difficulties, it’s essential we define the neural underpinnings of these conditions, and identify the areas they overlap and where they are very distinct,” said senior author Pratik Mukherjee, M.D., Ph.D., a professor of radiology and biomedical imaging and bioengineering at UCSF.

SPD can be hard to pinpoint, as more than 90 percent of children with autism also are reported to have atypical sensory behaviors, and SPD has not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists.

Elysa Marco, UC San Francisco

“One of the most striking new findings is that the children with SPD show even greater brain disconnection than the kids with a full autism diagnosis in some sensory-based tracts,” said Elysa Marco, M.D., cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital San Francisco and the study’s corresponding author. “However, the children with autism, but not those with SPD, showed impairment in brain connections essential to the processing of facial emotion and memory.”

Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with emotional regulation. Furthermore, a sound that is an irritant one day can be tolerated the next. The disease can be baffling for parents and has been a source of much controversy for clinicians who debate whether it constitutes its own disorder, according to the researchers.

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Anesthesia’s effects on brain cell connections are temporary, study suggests


Addresses concerns that exposing kids to anesthetics may increase susceptibility to learning disabilities.

Hippocampal neuron in culture. Dendrites are green, dendritic spines red, and DNA in cell’s nucleus is blue.(Credit: Shelley Halpain, UC San Diego)

A study of juvenile rat brain cells suggests that the effects of a commonly used anesthetic drug on the connections between brain cells are temporary.

The study, published in this week’s issue of the journal PLOS ONE, was conducted by biologists at UC San Diego and Weill Cornell Medical College in New York in response to concerns, arising from multiple studies on humans over the past decade, that exposing children to general anesthetics may increase their susceptibility to long-term cognitive and behavioral deficits, such as learning disabilities.

An estimated six million children, including 1.5 million infants, undergo surgery in the United States requiring general anesthesia each year and a least two large-scale clinical studies are now under way to determine the potential risks to children and adults.

“Since these procedures are unavoidable in most cases, it’s important to understand the mechanisms associated with the potentially toxic effects of anesthetics on the developing brain, and on the adult brain as well,” said Shelley Halpain, a professor of biology at UC San Diego and the Sanford Consortium for Regenerative Medicine, who co-headed the investigation. “Because the clinical studies haven’t been completed, preclinical studies, such as ours, are needed to define the effects of various anesthetics on brain structure and function.”

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Advancing brain surgery to benefit patients


Minimally invasive brain surgery at UC San Diego Health System.

Clark Chen, UC San Diego

In a milestone procedure, neurosurgeons at UC San Diego Health System have integrated advanced 3-D imaging, computer simulation and next-generation surgical tools to perform a highly complex brain surgery through a small incision to remove deep-seated tumors. This is the first time this complex choreography of technologies has been brought together in an operating room in California.

“Tumors located at the base of the skull are particularly challenging to treat due to the location of delicate anatomic structures and critical blood vessels,” said neurosurgeon Clark C. Chen, M.D., Ph.D., UC San Diego Health System. “The conventional approach to excising these tumors involves long skin incisions and removal of a large piece of skull. This new minimally invasive approach is far less radical. It decreases the risk of the surgery and shortens the patient’s hospital stay.”

“A critical part of this surgery involves identifying the neural fibers in the brain, the connections that allow the brain to perform its essential functions. The orientation of these fibers determines the trajectory to the tumor,” said Chen, vice chairman of academic affairs for the Division of Neurosurgery at UC San Diego School of Medicine. “We visualized these fibers with restriction spectrum imaging, a proprietary technology developed at UC San Diego. Color-coded visualization of the tracts allows us to plot the safest path to the tumor.”

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$1M grant funds study into neurochemistry behind addiction


Research could lead to improved therapies for those inclined toward addictive behaviors.

We’ve all heard the term “addictive personality,” and many of us know individuals who are consistently more likely to take the extra drink or pill that puts them over the edge. But the specific balance of neurochemicals in the brain that spurs him or her to overdo it is still something of a mystery.

“There’s not really a lot we know about specific molecules that are linked to vulnerability to addiction,” said Tod Kippin, a neuroscientist at UC Santa Barbara who studies cocaine addiction. In a general sense, it is understood that animals — humans included — take substances to derive that pleasurable rush of dopamine, the neurochemical linked with the reward center of the brain. But, according to Kippin, that dopamine rush underlies virtually any type of reward animals seek, including the kinds of urges we need to have in order to survive or propagate, such as food, sex or water. Therefore, therapies that deal with that reward system have not been particularly successful in treating addiction.

However, thanks to a collaboration between UCSB researchers Kippin; Tom Soh, professor of mechanical engineering and of materials; and Kevin Plaxco, professor of chemistry and biochemistry — and funding from a $1 million grant from the W. M. Keck Foundation — the neurochemistry of addiction could become a lot less mysterious and a lot more specific. Their study, “Continuous, Real-Time Measurement of Psychoactive Molecules in the Brain,” could, in time, lead to more effective therapies for those who are particularly inclined toward addictive behaviors.

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Researchers find epigenetic tie to neuropsychiatric disorders


Flawed dopamine signaling linked to mass alteration of gene activity in prefrontal cortex.

“Our work presents new leads to understanding neuropsychiatric disorders,” UC Irvine's Emiliana Borrelli said.

Dysfunction in dopamine signaling profoundly changes the activity level of about 2,000 genes in the brain’s prefrontal cortex and may be an underlying cause of certain complex neuropsychiatric disorders, such as schizophrenia, according to UC Irvine scientists.

This epigenetic alteration of gene activity in brain cells that receive this neurotransmitter showed for the first time that dopamine deficiencies can affect a variety of behavioral and physiological functions regulated in the prefrontal cortex.

The study, led by Emiliana Borrelli, a UCI professor of microbiology & molecular genetics, appears online in the journal Molecular Psychiatry.

“Our work presents new leads to understanding neuropsychiatric disorders,” Borrelli said. “Genes previously linked to schizophrenia seem to be dependent on the controlled release of dopamine at specific locations in the brain. Interestingly, this study shows that altered dopamine levels can modify gene activity through epigenetic mechanisms despite the absence of genetic mutations of the DNA.”

Dopamine is a neurotransmitter that acts within certain brain circuitries to help manage functions ranging from movement to emotion. Changes in the dopaminergic system are correlated with cognitive, motor, hormonal and emotional impairment. Excesses in dopamine signaling, for example, have been identified as a trigger for neuropsychiatric disorder symptoms.

Borrelli and her team wanted to understand what would happen if dopamine signaling was hindered. To do this, they used mice that lacked dopamine receptors in midbrain neurons, which radically affected regulated dopamine synthesis and release.

The researchers discovered that this receptor mutation profoundly altered gene expression in neurons receiving dopamine at distal sites in the brain, specifically in the prefrontal cortex. Borrelli said they observed a remarkable decrease in expression levels of some 2,000 genes in this area, coupled with a widespread increase in modifications of basic DNA proteins called histones – particularly those associated with reduced gene activity.

Borrelli further noted that the dopamine receptor-induced reprogramming led to psychotic-like behaviors in the mutant mice and that prolonged treatment with a dopamine activator restored regular signaling, pointing to one possible therapeutic approach.

The researchers are continuing their work to gain more insights into the genes altered by this dysfunctional dopamine signaling.

Borrelli is affiliated with UCI’s Center for Epigenetics & Metabolism and manages the INSERM/UCI U904 laboratory there. Karen Brami-Cherrier, Andrea Anzalone, Maria Ramos and Fabio Macciardi of UCI, as well as Ignasi Forne and Axel Imhof of Ludwig Maximilian University of Munich, contributed to the study, which received support from the National Institutes of Health (grant DA024689) and INSERM (grant 44790).

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Qualcomm Institute awards seed grants


35 UC San Diego projects receive grants to build clusters in brain, medical, robotics research.

The Qualcomm Institute at UC San Diego has given the green light to 35 new projects that are part of the institute’s Calit2 Strategic Research Opportunities (CSRO) program. Each one-year seed grant is worth up to $50,000 in support for researchers in areas of critical interest to the research mission of the institute — and the university. (The Qualcomm Institute is the UC San Diego division of the California Institute for Telecommunications and Information Technology, or Calit2.)

The new projects were selected from a field of 70 proposals put forward by eligible professors and research scientists. Effective July 1, the 35 projects were awarded grants valued at more than $1,673,000.

“Reviewers were impressed with the quality of this year’s proposals, which were largely responsive to the areas where we want to take the institute in the next couple of years,” said Qualcomm Institute Director Ramesh Rao, a professor of electrical and computer engineering in the Jacobs School of Engineering. “In particular, the funded projects will allow us to participate actively in campus-wide brain, medical and robotics research initiatives. We look at it as a down payment, because our researchers will be able to leverage these investments and compete for larger federal grants that are needed to advance the state of the art in these important areas.”

Most of the funding for the CSRO program was earmarked from private support received by the Qualcomm Institute, notably from Qualcomm Inc., the Qualcomm Foundation and The Legler Benbough Foundation.

CSRO grants to PIs typically involve a cash portion (including fellowships) and in-kind support in the form of Qualcomm Institute services, personnel or the use of facilities. As part of the cash support, roughly $469,200 will go directly to graduate student researchers in the form of CSRO Fellowships for full- or part-time work on 18 of the new projects. Another $652,500 was allocated for services provided by the Qualcomm Institute itself.

Among the 35 winning proposals, at least 10 are directly related to brain research – reflecting the importance that the institute places on the newly established campus Center for Brain Activity Mapping (CBAM).

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‘Support cells’ in brain play important role in Down syndrome


New research also suggests common antibiotic might help treat the genetic defect.

Researchers from UC Davis School of Medicine and Shriners Hospitals for Children – Northern California have identified a group of cells in the brain that they say plays an important role in the abnormal neuron development in Down syndrome. After developing a new model for studying the syndrome using patient-derived stem cells, the scientists also found that applying an inexpensive antibiotic to the cells appears to correct many abnormalities in the interaction between the cells and developing neurons.

The findings, which focused on support cells in the brain called astroglial cells, appear online today in Nature Communications.

“We have developed a human cellular model for studying brain development in Down syndrome that allows us to carry out detailed physiological studies and screen possible new therapies,” said Wenbin Deng, associate professor of biochemistry and molecular medicine and principal investigator of the study. “This model is more realistic than traditional animal models because it is derived from a patient’s own cells.”

Down syndrome is the most common chromosomal cause of mild to moderate intellectual disabilities in the United States, where it occurs in one in every 691 live births. It develops when a person has three copies of the 21st chromosome instead of the normal two. While mouse models have traditionally been used in studying the genetic disorder, Deng said the animal model is inadequate because the human brain is more complicated, and much of that complexity arises from astroglia cells, the star-shaped cells that play an important role in the physical structure of the brain as well as in the transmission of nerve impulses.

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