Treating traumatic brain injury

January 6, 2017 by Ryan Shelton, Duke University

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 cannot directly treat the inflammation.

Some people can walk out okay after suffering from this injury, yet others can become comatose or may even die. This raises the intriguing question: why do people with similar injuries end up with vastly different outcomes? TBI affects nearly 2 million Americans every year and nearly 52,000 of these injuries are fatal.

"To a certain extent, the way the body responds to injury is probably genetically hardwired," said Dr. Daniel Laskowitz, a neurologist at Duke who has been working on the mysteries of traumatic brain injuries for two decades. He said in medical school, he preferred the approach of treating the whole body and not super specializing. He chose to work specifically with brain injury because he could treat patients with other conditions along with brain injury.

One of Dr. Laskowitz's first publications was about brain injury. As a fellow training in neurology in the mid-1990s, he looked at genetic factors that could make a difference in the outcome of a brain injury and found that genetic variation in a protein called apolipoprotein E (apoE) played a role. ApoE comes in three slightly different flavors, and one of the common forms of apoE (apoE4) was associated with bad outcomes after brain injury. This raised the question of what apoE was doing in the brain to affect outcome after injury.

In 1997, he published an article about the effect of apoE on mice suffering a stroke and found that mice with the apoE allele had a better recovery than mice with an apoE deficiency. These findings were later repeated in an article in 2001,which found that following , animals with apoE had better outcomes than animals without this protein.

Since it was found that apoE could improve an injured patient's neurologic outcomes, it became a model for medication to treat brain injuries. However, apoE does not easily cross the blood-brain-barrier, making it a challenging molecule to dispense as a drug.

Dr. Laskowitz's lab has spent almost a decade looking at how apoE works. They have recently developed a peptide made of 5 amino acids, CN-105, that is based off of this protein and is able to cross the blood-brain-barrier, giving it the potential to be distributed as a treatment. This has been tested in mice and shown to improve outcomes.

In July, CN-105 completed a first phase clinical trial and found that drug administration was safe and well tolerated. In the coming year, a phase 2 study will look at whether CN-105 improves outcomes in patients with brain hemorrhages.

The plan is to give the peptide through an IV every six hours for three days, the time period when most of the swelling happens after injury.

Dr. Laskowitz's research has already had a significant impact on the treatment of , and hopefully, this new medication could be another great contribution to this field.

Explore further: Protein linked to high risk of Alzheimer's can be removed from brain without hindering learning

More information: Beilei Lei et al. Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage, Scientific Reports (2016). DOI: 10.1038/srep34834

James J Donkin et al. Mechanisms of cerebral edema in traumatic brain injury: therapeutic developments, Current Opinion in Neurology (2010). DOI: 10.1097/WCO.0b013e328337f451

David Cederberg et al. What has inflammation to do with traumatic brain injury?, Child's Nervous System (2009). DOI: 10.1007/s00381-009-1029-x

Related Stories

Protein linked to high risk of Alzheimer's can be removed from brain without hindering learning

October 4, 2016
A protein linked to higher risk of Alzheimer's can be removed from the brains of mice without hindering memory and learning, according to a study that addresses whether potential therapeutics targeting this protein would ...

Early intervention in brain inflammatory pathways may improve stroke recovery

November 28, 2016
Intracerebral hemorrhage is a type of stroke characterized by the rupture of a blood vessel within the brain. When the brain is exposed to blood, local immune cells become activated, triggering inflammation that promotes ...

Biomarkers to assess degree of brain injury in postconcussion syndrome

September 19, 2016
A new study published online by JAMA Neurology included 16 professional Swedish hockey players and examined whether persistent symptoms after mild traumatic brain injury were associated with brain injury as evaluated by cerebrospinal ...

Normal cognition in patient without apolipoprotein E, risk factor for Alzheimer's

August 11, 2014
A 40-year-old California man exhibits normal cognitive function although he has no apolipoprotein E (apoE), which is believed to be important for brain function but a mutation of which is also a known risk factor for Alzheimer ...

Craniectomy after head injury reduces risk of death from brain swelling

September 8, 2016
Craniectomy – a surgical procedure in which part of the skull is removed to relieve brain swelling – significantly reduces the risk of death following traumatic brain injury, an international study led by the University ...

Recommended for you

Use of electrical brain stimulation to foster creativity has sweeping implications

September 18, 2018
What is creativity, and can it be enhanced—safely—in a person who needs a boost of imagination? Georgetown experts debate the growing use of electrical devices that stimulate brain tissue, and conclude there is potential ...

Engineers decode conversations in brain's motor cortex

September 18, 2018
How does your brain talk with your arm? The body doesn't use English, or any other spoken language. Biomedical engineers are developing methods for decoding the conversation, by analyzing electrical patterns in the motor ...

Team identifies brain's lymphatic vessels as new avenue to treat multiple sclerosis

September 17, 2018
Lymphatic vessels that clean the brain of harmful material play a crucial role in the development and progression of multiple sclerosis, new research from the University of Virginia School of Medicine suggests. The vessels ...

Circuit found for brain's statistical inference about motion

September 17, 2018
As the eye tracks a bird flying past, the muscles that pan the eyeballs to keep the target in focus set their pace not only on the speed they see, but also on a reasonable estimate of the speed they expect from having watched ...

Mouse study reveals that activity, not rest, speeds recovery after brain injury

September 17, 2018
When recovering from a brain injury, getting back in the swing of things may be more effective than a prolonged period of rest, according to a new Columbia study in mice. These findings offer a compelling example of the brain's ...

Fine-tuned sense of smell relies on timing

September 17, 2018
If you can tell the difference between a merlot and a cabernet franc just by smell, it's probably all in the timing.

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.