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

September 13, 2017, Perelman School of Medicine at the University of Pennsylvania

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 swelling, and less evidence of 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 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.

Explore further: Heparin stimulates food intake and body weight gain in mice

Related Stories

Heparin stimulates food intake and body weight gain in mice

September 5, 2017
Heparin is a medication widely used to prevent blood clotting; it is named after and mimics the naturally occurring anticoagulant in the body. However, research published today in Cell Reports shows a novel role of heparin ...

Apixaban lowers stroke risk in atrial fibrillation patients undergoing cardioversion

August 28, 2017
Apixaban lowers the risk of stroke compared to warfarin in anticoagulation-naïve patients with atrial fibrillation scheduled for elective cardioversion, according to late-breaking results from the EMANATE trial presented ...

Heparin derived from cattle is equivalent to heparin from pigs, study finds

October 5, 2016
As demand for the widely used blood thinning drug heparin continues to grow, experts worry of possible shortages of the essential medication.

Findings from the BRIGHT trial published

March 17, 2015
Data from the BRIGHT trial published today in the Journal of the American Medical Association demonstrated that bivalirudin was superior to both heparin monotherapy and heparin plus tirofiban for patients with acute myocardial ...

Treating traumatic brain injury

January 6, 2017
After a traumatic brain injury (TBI), the brain produces an inflammatory response. This prolonged swelling is known as cerebral edema and can be fatal. Unfortunately, the only medications available just address symptoms and ...

Heparin derivative suppresses neuroblastoma tumor growth

June 17, 2014
Researchers at Duke Medicine have identified a new strategy for treating neuroblastoma using a modified version of heparin, a century-old injectable drug that thins the blood to prevent clots from forming.

Recommended for you

New neurons in the adult brain are involved in sensory learning

February 23, 2018
Although we have known for several years that the adult brain can produce new neurons, many questions about the properties conferred by these adult-born neurons were left unanswered. What advantages could they offer that ...

Neuroscientists discover a brain signal that indicates whether speech has been understood

February 22, 2018
Neuroscientists from Trinity College Dublin and the University of Rochester have identified a specific brain signal associated with the conversion of speech into understanding. The signal is present when the listener has ...

Study in mice suggests personalized stem cell treatment may offer relief for multiple sclerosis

February 22, 2018
Scientists have shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, help reduce inflammation and may be able to help repair damage caused by multiple sclerosis ...

Nolan film 'Memento' reveals how the brain remembers and interprets events from clues

February 22, 2018
Key repeating moments in the film give viewers the information they need to understand the storyline. The scenes cause identical reactions in the viewer's brain. The results deepen our understanding of how the brain functions, ...

Biomarker, clues to possible therapy found in novel childhood neurogenetic disease

February 22, 2018
Researchers studying a rare genetic disorder that causes severe, progressive neurological problems in childhood have discovered insights into biological mechanisms that drive the disease, along with early clues that an amino ...

A look at the space between mouse brain cells

February 22, 2018
Between the brain's neurons and glial cells is a critical but understudied structure that's been called neuroscience's final frontier: the extracellular space. With a new imaging paradigm, scientists can now see into and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.