New Treatment for Traumatic Brain Injury Shows Promise in Animals

A new drug is showing promise in shielding against the harmful effects of traumatic brain injury (TBI) in rats, according to a study that was released today and will be presented at the American Academy of Neurology’s 64th Annual Meeting in New Orleans April 21 to April 28, 2012.

“There are currently no primary treatments for TBI, so this research provides hope that effective treatments can be developed,” said study author Michael Kaufman, a second year medical student at Wayne State University School of Medicine in Detroit and a member of the American Academy of Neurology. The principal investigator on the study is Christian Kreipke, MD, also with Wayne State University School of Medicine.

Traumatic brain injury causes a decrease in blood flow in the cerebrum of the brain, which if prolonged, can cause permanent cell dysfunction and death. A receptor in the brain called endothelin receptor A (ETrA) contributes to the restriction of blood flow as early as four hours after a brain injury. The new drug, called clazosentan, is thought to specifically block these receptors.

Researchers gave brain-injured rats the drug clazosentan through an intravenous (IV) line at several different points in time after the injury. Next, they measured the rat’s blood flow in the hippocampus and sensory motor cortex with an MRI brain scan and tested their behavior in learning a maze.

Preliminary data from the study found that clazosentan decreased the effects of the traumatic brain injury on blood flow to the hippocampus by 25 percent at four hours and 23 percent at 48 hours after TBI. However, giving the rats the drug at 12 hours post-injury caused some to improve, while others worsened or remained the same. In the trial, the drug was most effective when given at two hours post-injury and again at 24 hours after the trauma. The rats also performed better on the maze test when given the drug at two and 24 hours post-injury.

What is Traumatic Brain Injury?
Traumatic brain injury (TBI), a form of acquired brain injury, occurs when a sudden trauma causes damage to the brain. TBI can result when the head suddenly and violently hits an object, or when an object pierces the skull and enters brain tissue.  Symptoms of a TBI can be mild, moderate, or severe, depending on the extent of the damage to the brain.  A person with a mild TBI may remain conscious or may experience a loss of consciousness for a few seconds or minutes. Other symptoms of mild TBI include headache, confusion, lightheadedness, dizziness, blurred vision or tired eyes, ringing in the ears, bad taste in the mouth, fatigue or lethargy, a change in sleep patterns, behavioral or mood changes, and trouble with memory, concentration, attention, or thinking.  A person with a moderate or severe TBI may show these same symptoms, but may also have a headache that gets worse or does not go away, repeated vomiting or nausea, convulsions or seizures, an inability to awaken from sleep, dilation of one or both pupils of the eyes, slurred speech, weakness or numbness in the extremities, loss of coordination, and increased confusion, restlessness, or agitation.

Is there any treatment?
Anyone with signs of moderate or severe TBI should receive medical attention as soon as possible. Because little can be done to reverse the initial brain damage caused by trauma, medical personnel try to stabilize an individual with TBI and focus on preventing further injury. Primary concerns include insuring proper oxygen supply to the brain and the rest of the body, maintaining adequate blood flow, and controlling blood pressure. Imaging tests help in determining the diagnosis and prognosis of a TBI patient. Patients with mild to moderate injuries may receive skull and neck X-rays to check for bone fractures or spinal instability. For moderate to severe cases, the imaging test is a computed tomography (CT) scan. Moderately to severely injured patients receive rehabilitation that involves individually tailored treatment programs in the areas of physical therapy, occupational therapy, speech/language therapy, physiatry (physical medicine), psychology/psychiatry, and social support.

“This research is the foundation for future clinical trials that will investigate the possibilities of using clazosentan in the treatment of TBI,” said Kaufman.

The study was supported by the American Academy of Neurology, the National Institutes of Health, and the U.S. Department of Veterans Affairs.

National TBI Estimates
Each year, an estimated 1.7 million people sustain a TBI annually.

Of them:

52,000 die,
275,000 are hospitalized, and
1.365 million, nearly 80%, are treated and released from an emergency department.

TBI is a contributing factor to a third (30.5%) of all injury-related deaths in the United States.

About 75% of TBIs that occur each year are concussions or other forms of mild TBI.

*The number of people with TBI who are not seen in an emergency department or who receive no care is unknown.

The American Academy of Neurology, an association of more than 25,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer’s disease, epilepsy, Parkinson’s disease and multiple sclerosis.

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Source: American Academy of Neurology (AAN)

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