Home  |  Top News  |  Most Popular  |  Video  |  Multimedia  |  News Feeds  |  Feedback
  Medicine  |  Nature & Earth  |  Biology  |  Technology & Engineering  |  Space & Planetary  |  Psychology  |  Physics & Chemistry  |  Economics  |  Archaeology
Top > Medicine, Health Care > Gladstone Scientists Identify Key Biological… >

Gladstone Scientists Identify Key Biological Mechanism in Multiple Sclerosis

Published: November 29, 2012.
Released by Gladstone Institutes  

SAN FRANCISCO, CA—November 27, 2012—Scientists at the Gladstone Institutes have defined for the first time a key underlying process implicated in multiple sclerosis (MS)—a disease that causes progressive and irreversible damage to nerve cells in the brain and spinal cord. This discovery offers new hope for the millions who suffer from this debilitating disease for which there is no cure.

Researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, have identified in animal models precisely how a protein that seeps from the blood into the brain sets off a response that, over time, causes the nerve cell damage that is a key indicator of MS. These findings, which are reported in the latest issue of Nature Communications, lay the groundwork for much-needed therapies to treat this disease.

MS, which afflicts more than two million people worldwide, develops when the body's immune system attacks the brain. This attack damages nerve cells, leading to a host of symptoms including numbness, fatigue, difficulty walking, paralysis and loss of vision. While some drugs can delay these symptoms, they do not treat the disease's underlying cause—which researchers are only just beginning to understand.

"To successfully treat MS, we must first identify what triggers the disease and what enables its progression," said Dr. Akassoglou, who also directs the Gladstone Center for In Vivo Imaging Research and is a professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "Here, we have shown that the leakage of blood in the brain acts as an early trigger that sets off the brain's inflammatory response—creating a neurotoxic environment that damages nerve cells."

Dr. Akassoglou and her team reached this conclusion by using advanced imaging techniques to monitor the disease's progression in the brain and spinal cord of mice modified to mimic the signs of MS. Traditional techniques only show "snapshots" of the disease's pathology. However, this analysis allows researchers to study individual cells within the living brain—and to monitor in real-time what happens to these cells as the disease worsens over time.

"In vivo imaging analysis let us observe in real-time which molecules crossed the blood-brain barrier," said Dimitrios Davalos, PhD, Gladstone staff research scientist, associate director of the imaging center and the paper's lead author. "Importantly, this analysis helped us identify the protein fibrinogen as the key culprit in MS, by demonstrating how its entry into the brain through leaky blood vessels impacted the health of individual nerve cells."

Fibrinogen, a blood protein that is involved in coagulation, is not found in the healthy brain. In vivo imaging over different stages of disease revealed, however, that a disruption in the blood-brain barrier allows blood proteins—and specifically fibrinogen—to seep into the brain. Microglia—immune cells that act as the brain's first line of defense—initiate a rapid response to fibrinogen's arrival. They release large amounts of chemically reactive molecules called 'reactive oxygen species.' This creates a toxic environment within the brain that damages nerve cells and eventually leads to the debilitating symptoms of MS.

Importantly, the team found a strategy to halt this process by genetically modifying fibrinogen in the animal models. This strategy disrupted the protein's interaction with the microglia without affecting fibrinogen's essential role as a blood coagulant. In these models, the microglia did not react to fibrinogen's arrival and did not create a toxic environment. As a result, the mice failed to show the type of progressive nerve cell damage seen in MS.

"Dr. Akassoglou's work reveals a novel target for treating MS—which might protect nerve cells and allow early intervention in the disease process," said Ursula Utz, PhD, MBA, a program director at The National Institutes of Health's National Institute of Neurological Disorders and Stroke, which provided funding for this research.

"Indeed, targeting the fibrinogen-microglia interactions to halt nerve-cell damage could be a new therapeutic strategy," said Dr. Akassoglou. "At present we are working to develop new approaches that specifically target the damaging effects of fibrinogen in the brain. We also continue to use in vivo imaging techniques to further enhance our understanding of what triggers the initiation and progression of MS. "




The above story is based on materials provided by Gladstone Institutes.

Translate this page: Chinese French German Italian Japanese Korean Portuguese Russian Spanish


comments powered by Disqus


Related »

Neonatal 
7/11/12 
Blood-brain Barrier Less Permeable in Newborns Than Adults After Acute Stroke
The ability for substances to pass through the blood-brain barrier is increased after adult stroke, but not after neonatal stroke, according to a new study the UCSF that will …
Barrier 
5/14/14 
Possible New Plan of Attack for Opening And Closing the Blood-brain Barrier
Like a bouncer at an exclusive nightclub, the blood-brain barrier allows only select molecules to pass from the bloodstream into the fluid that bathes the brain. Vital nutrients get …
Blood-Brain 
3/8/11 
★ 
University of South Florida Researchers Find Blood-brain Barrier Damaged by Disease
A study into the effects of Sanfilippo Syndrome type B (MPS III B) has found that the barrier responsible for protecting the brain from the entry of harmful blood-borne …
Endothelial 
12/6/12 
Research on Blood Vessel Proteins Holds Promise for Controlling 'Blood-brain Barrier'
Working with mice, Johns Hopkins researchers have shed light on the activity of a protein pair found in cells that form the walls of blood vessels in the brain …
Cells 
2/4/13 
Experimental Therapy Crosses Blood-brain Barrier to Treat Neurological Disease
CINCINNATI – Researchers have overcome a major challenge to treating brain diseases by engineering an experimental molecular therapy that crosses the blood-brain barrier to reverse neurological lysosomal storage disease …
Tight 
4/17/14 
Study IDs New Cause of Brain Bleeding Immediately After Stroke
Irvine, Calif., April 17, 2014 — By discovering a new mechanism that allows blood to enter the brain immediately after a stroke, researchers at UC Irvine and the Salk …
Ultrasound 
3/13/12 
JoVE Shows How Researchers Open the Brain to New Treatments
One of the trickiest parts of treating brain conditions is the blood brain barrier, a blockade of cells that prevent both harmful toxins and helpful pharmaceuticals from getting to …
Mir-155 
6/2/14 
Why Inflammation Leads to a Leaky Blood-brain Barrier: MicroRNA-155
Until now, scientists have not known exactly how inflammation weakens the Blood-Brain Barrier, allowing toxins and other molecules access to the brain. A new research report appearing in the …
Fibrinogen 
11/27/12 
NIH-funded Researchers Show Possible Trigger for MS Nerve Damage
High-resolution real-time images show in mice how nerves may be damaged during the earliest stages of multiple sclerosis. The results suggest that the critical step happens when fibrinogen, a …
Model 
12/5/14 
Blood Brain Barrier on a Chip Could Stand in for Children in Pediatric Brain Research
In the human brain, the BBB is not the Better Business Bureau but the blood brain barrier and the BBB is serious business in human physiology. The human BBB …
Umbilical 
6/1/10 
★ 
Mannitol Boosts Effectiveness of Potential Cord Blood Treatment for Cerebral Palsy in Lab Animals
Tampa, Fla. (June 1, 2010) – The sugar-alcohol compound mannitol improved the therapeutic effectiveness of human umbilical cord blood cells injected into neonatal rat models of cerebral palsy, reports …
More » 
 
© Newsline Group  |  About  |  Privacy Policy  |  Feedback  |  Mobile