Nav: Home

Study shows modified blood thinner reduces the impact of traumatic brain injury in mice

September 13, 2017

PHILADELPHIA-- A chemically modified version of the common blood thinner heparin may be the first promising method of preventing the harmful cascade of destruction to brain tissue that commonly follows traumatic brain injury (TBI), according to new research findings. Though there is currently no drug therapy to prevent the repercussions that can occur in the days and weeks after TBI, researchers at the Perelman School of Medicine at the University of Pennsylvania showed that mice treated with a modified version of heparin with very low coagulant activity (known as 2-O, 3-O desulfated heparin, ODSH or CX-01) had less brain swelling and inflammation, and less evidence of brain damage, compared to mice that received saline. Results of the study will be presented in Baltimore this week at the annual meeting of the American Association for the Surgery of Trauma.

Traumatic brain injury (TBI), which accounts for more than 2.5 million emergency room visits every year in the United States, often triggers inflammation and other harmful processes in the brain, causing further damage and cognitive deterioration long after the initial injury. Ordinary heparin has anti-inflammatory properties and has been shown to protect various organs after injury, but its blood-thinning effect makes it problematic for use in injured brains, where a bleed could be fatal. ODSH has only a small fraction of heparin's anticoagulant effect, and thus seemed a good bet as a safer alternative. Prior studies in animal models of heart attack, stroke, and pneumonia have found evidence that ODSH has a heparin-like anti-inflammatory effect, without the risk of hemorrhages.

"When I first presented a heparin-TBI study, experts in treating these injuries laughed, and said 'that'll be the day, when we give heparin to TBI patients'," said study senior author Jose M. Pascual, MD, PhD, an associate professor of surgery at Penn Medicine. "But, there's an exciting possibility here that the molecule ODSH retains heparin's benefits in reducing swelling and inflammation but without the anticoagulant activity that could cause bleeding."

In the study, Pascual and colleagues treated mice for 48 hours after experimental TBI with ODSH or, as a control, ordinary saline. Immediately following the two days of treatment, the animals that had received ODSH showed less evidence of white blood cell infiltration into the brain via cerebral vessels, less evidence of cerebral vessel leakage, less brain swelling, and less evidence of brain damage on a standard neurological test, compared to the control mice.

In a cognitive test called the Morris Water Maze, 17 days after their TBI, the ODSH-treated animals also performed markedly better than the controls, doing on average almost as well as mice who had not experienced a TBI.

"We saw no evidence of bleeding," Pascual said.

Pascual and colleagues at Penn Medicine are now hoping to set up a clinical trial of ODSH to test its effectiveness in people with TBI.

Heparin has been in clinical use since the 1930s as an anticoagulant. But it is a natural molecule--a carbohydrate secreted by white blood cells called mast cells and basophils--and has multiple biological effects, including a reduction of inflammation after injury. In a study published last year, Pascual and colleagues found evidence that ordinary heparin protects mice from the inflammation, swelling and cognitive deficits caused by experimental TBI.

The company that produces ODSH, Cantex Pharmaceuticals Inc, is currently testing ODSH in patients with blood cancers, specifically, acute myeloid leukemia and myelodysplastic syndrome.

"The company already has safety data on ODSH from those trials in cancer patients, so we're hoping that for TBI we can go straight to a phase II study of the drug's effectiveness and optimal dose," Pascual said.

-end-

Co-authors of the study were Katsuhiro Nagata, Yujin Suto, John Cognetti, Kevin D. Browne, Victoria E. Johnson, Lewis Kaplan, and Douglas H. Smith, all of Penn Medicine; Kenichiro Kumasaka of Tokyo Medical University Hachioji Medical Center; and Joshua Marks of the Sidney Kimmel Medical College at Thomas Jefferson University.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.

University of Pennsylvania School of Medicine

Related Traumatic Brain Injury Articles:

New test may quickly identify mild traumatic brain injury with underlying brain damage
A new test using peripheral vision reaction time could lead to earlier diagnosis and more effective treatment of mild traumatic brain injury, often referred to as a concussion.
Studies uncover long-term effects of traumatic brain injury
Doctors are beginning to get answers to the question that every parent whose child has had a traumatic brain injury wants to know: What will my child be like 10 years from now?
People with traumatic brain injury approximately 2.5 times more likely to be incarcerated
People who have suffered a traumatic brain injury are approximately 2.5 times more likely to be incarcerated in a federal correctional facility in Canada than people who have not, a new study has found.
Traumatic brain injury associated with long-term psychosocial outcomes
Traumatic brain injury (TBI) during youth is associated with elevated risks of impaired adult functioning, according to a longitudinal study published in PLOS Medicine.
Curbing the life-long effects of traumatic brain injury
A fall down the stairs, a car crash, a sports injury or an explosive blast can all cause traumatic brain injury (TBI).
Is traumatic brain injury associated with late-life neurodegenerative conditions?
Traumatic brain injury (TBI) with loss of consciousness was not associated with late-life mild cognitive impairment, Alzheimer disease or dementia but it appeared to be associated with increased risk for other neurodegenerative and neuropathologic findings, according to a new article published online by JAMA Neurology.
Link found between traumatic brain injury and Parkinson's, but not Alzheimer's
Traumatic brain injury (TBI) with a loss of consciousness (LOC) may be associated with later development of Parkinson's disease but not Alzheimer's disease or incident dementia.
Novel peptide protects cognitive function after mild traumatic brain injury
Scientists at the Hebrew University of Jerusalem have shown that a single dose of a new molecule can protect the brain from inflammation and cognitive impairments following mild traumatic brain injury.
Allen Institute releases powerful new data on the aging brain and traumatic brain injury
The Allen Institute for Brain Science has announced major updates to its online resources available at brain-map.org, including a new resource on Aging, Dementia and Traumatic Brain Injury in collaboration with UW Medicine researchers at the University of Washington, and Group Health.
Developing tools to screen traumatic brain injury therapies
University of Houston biologist Amy Sater will be developing a model for studying traumatic brain injury, thanks to a two-year, $386,000 grant from the Robert J.

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: Radiolab

Oliver Sipple
One morning, Oliver Sipple went out for a walk. A couple hours later, to his own surprise, he saved the life of the President of the United States. But in the days that followed, Sipple's split-second act of heroism turned into a rationale for making his personal life into political opportunity. What happens next makes us wonder what a moment, or a movement, or a whole society can demand of one person. And how much is too much?  Through newly unearthed archival tape, we hear Sipple himself grapple with some of the most vexing topics of his day and ours - privacy, identity, the freedom of the press - not to mention the bonds of family and friendship.  Reported by Latif Nasser and Tracie Hunte. Produced by Matt Kielty, Annie McEwen, Latif Nasser and Tracie Hunte. Special thanks to Jerry Pritikin, Michael Yamashita, Stan Smith, Duffy Jennings; Ann Dolan, Megan Filly and Ginale Harris at the Superior Court of San Francisco; Leah Gracik, Karyn Hunt, Jesse Hamlin, The San Francisco Bay Area Television Archive, Mike Amico, Jennifer Vanasco and Joey Plaster. Support Radiolab today at Radiolab.org/donate.
Now Playing: TED Radio Hour

Future Consequences
From data collection to gene editing to AI, what we once considered science fiction is now becoming reality. This hour, TED speakers explore the future consequences of our present actions. Guests include designer Anab Jain, futurist Juan Enriquez, biologist Paul Knoepfler, and neuroscientist and philosopher Sam Harris.