Posts tagged brain hemorrhage
Articles and news from the latest research reports.
Experimental drug reduces brain damage in rodents
An experimental drug called 3K3A-APC appears to reduce brain damage, eliminate brain hemorrhaging and improve motor skills in older stroke-afflicted mice and stroke-afflicted rats with comorbid conditions such as hypertension, according to a new study from Keck Medicine of USC.
The report, which appears online in the journal Stroke, provides additional evidence that 3K3A-APC may be used as a therapy for stroke in humans, either alone or in combination with the Food and Drug Administration (FDA)-approved clot-busting drug therapy known as tissue plasminogen activator (tPA). Clinical trials to test the drug’s efficacy in people experiencing acute ischemic stroke are expected to begin recruiting patients across the United States next year.
“Currently, tPA is the best treatment for stroke caused by a blocked artery, but it must be administered within three hours after stroke onset to be effective,” said Berislav Zlokovic, director of the Zilkha Neurogenetic Institute (ZNI) at the Keck School of Medicine of USC and the study’s lead investigator. “Because of this limited window, only a small fraction of those who suffer a stroke reach the hospital in time to be considered for tPA. Our studies show that 3K3A-APC extends tPA’s therapeutic window and counteracts tPA’s tendency to induce bleeding in the brains of animals having a stroke.”
Zlokovic is the scientific founder of ZZ Biotech, a Houston-based biotechnology company he co-founded with USC benefactor Selim Zilkha to develop biological treatments for stroke and other neurological ailments.
ZZ Biotech’s 3K3A-APC is a genetically engineered variant of the naturally occurring activated protein C (APC), which plays a role in the regulation of blood clotting and inflammation. 3K3A-APC has been shown to have a protective effect on the lining of blood vessels in rodent brains, which appears to help prevent bleeding caused by tPA.
In collaboration with Cedars-Sinai Medical Center and The Scripps Research Institute, Zlokovic and his team gave tPA — alone and in combination with 3K3A-APC — to mature female mice and male hypertensive rats four hours after stroke. They also gave 3K3A-APC in regular intervals up to seven days after stroke. The researchers measured the amount of brain damage, bleeding and motor ability of the rodents up to four weeks after stroke.
The researchers found that, under those conditions, tPA therapy alone caused bleeding in the brain and did not reduce brain damage or improve motor ability when compared to the control. The combination of tPA and 3K3A-APC, however, reduced brain damage by more than half, eliminated tPA-induced bleeding and significantly improved motor ability.
“Scientists all around the globe are studying potential stroke therapies, but very few have the robust preclinical data package that 3K3A-APC has,” said Kent Pryor, ZZ Biotech’s chief operating officer. “The results from Dr. Zlokovic’s studies have been very promising.”
Zlokovic’s team previously reported similar results in young, healthy male rodents. A Phase 1 trial testing the safety of 3K3A-APC in healthy human volunteers, led by study co-author Patrick D. Lyden of Cedars-Sinai concluded in February.
“We now have opened an investigational new drug application at the FDA to conduct a Phase 2 clinical trial of 3K3A-APC in patients experiencing acute ischemic stroke,” said Joe Romano, CEO and president of ZZ Biotech. “We are excited to see 3K3A-APC move from healthy volunteers to real patients suffering from this terrible disease.”
Technique Could Identify Patients at High Risk of Stroke or Brain Hemorrhage
Measuring blood flow in the brain may be an easy, noninvasive way to predict stroke or hemorrhage in children receiving cardiac or respiratory support through a machine called ECMO, according to a new study by researchers at Nationwide Children’s Hospital. Early detection would allow physicians to alter treatment and take steps to prevent these complications—the leading cause of death for patients on ECMO.
Short for extracorporeal membrane oxygenation, ECMO is used when a patient is unable to sustain enough oxygen in the blood supply due to heart failure, septic shock, or other life-threatening condition, said Nicole O’Brien, MD, a physician and scientist in critical care medicine at Nationwide Children’s and lead author of the study, which appears in a recent issue of the journal Pediatric Critical Care Medicine. The patient is connected to ECMO with tubes that carry the patient’s blood from a vein through the machine, where it is oxygenated and funneled back to the patient via an artery or vein that then distributes the oxygen-rich blood to vital organs and tissues.
The disease processes that lead someone to need ECMO are different, O’Brien noted, but it is used only after traditional therapies, such as a ventilator, fail. One of the biggest risks of ECMO is bleeding in the brain. Only 36 percent of children who suffer this complication survive, many left with permanent neurologic injury.
“Most of these patients are critically ill before they go on ECMO and often have low oxygen levels, low blood pressure and poor heart function, all of which can certainly lead to strokes,” said O’Brien, also an associate professor of clinical medicine at The Ohio State University College of Medicine. “Still, some patients develop problems and others don’t and we don’t understand why.”
To better understand the cause for these brain bleeds, O’Brien launched a pilot study to monitor cerebral blood flow using a transcranial doplar ultrasound machine, a portable, noninvasive technology that uses sound waves to measure the amount and speed of blood flowing through the brain. All patients on ECMO experience a change in cranial blood flow, but O’Brien wanted to see if those variations offered any hint as to why some patients had complications while others didn’t.
She measured cranial blood flow in 18 ECMO patients, taking the first reading within the patient’s first 24 hours on the machine, then again each day they received the treatment and one more time after ECMO therapy ended.
When she compared these measurements to normal cerebral blood flow rates for children in the same age group, she found significant differences. Thirteen of the children in the study developed no neurologic complications while on ECMO. In these children, cerebral blood flow was 40 percent to 50 percent lower than normal. But in the five patients who had either a stroke or brain hemorrhage while on ECMO, cerebral blood flow was 100 percent higher than normal.
The age of the child, length of time on ECMO or the underlying illness didn’t seem to matter. The only difference was that cerebral blood flow was dramatically increased in patients who ultimately had problems. While O’Brien found that interesting, the most intriguing finding was that the increase in blood flow occurred as long as two to six days before the patient began bleeding in the brain.
“That could give us a lot of lead time to prevent the brain bleeds or hemorrhages,” said O’Brien.
Physicians may decide to try to wean a patient off ECMO a little more quickly or change the dosage of anti-coagulant medication that all ECMO patients take.
Although O’Brien is excited about the results, she is careful to note that the findings are preliminary. She is planning a multi-center trial to see if the outcome will be the same in a larger study population.
“We still need to understand why these kids bleed and why they stroke,” said O’Brien. “This little piece of information is the very tip of the iceberg in terms of why that happens.”
(Source: nationwidechildrens.org)
Tests conducted on Israel’s Ariel Sharon reveal significant brain activity
A team of American and Israeli brain scientists tested former Israeli Prime Minister Ariel Sharon to assess his brain responses, using functional magnetic resonance imaging (fMRI). Surprisingly, Sharon showed significant brain activity.
The team consisted of Martin Monti, an assistant professor of psychology and neurosurgery at UCLA, professors Alon Friedman, Galia Avidan and Tzvi Ganel of the Zlotowski Center for Neuroscience at Israel’s Ben-Gurion University of the Negev, and Dr. Ilan Shelef, head of medical imaging at Israel’s Soroka University Medical Center.
The 84-year-old Sharon, presumed to be in a vegetative state since suffering a brain hemorrhage in 2006, was scanned last week to assess the extent and quality of his brain processing, using methods recently developed by Monti and his colleagues. The test lasted approximately two hours.
The scientists showed Sharon pictures of his family, had him listen to his son’s voice and used tactile stimulation to assess the extent to which his brain responded to external stimuli.
To their surprise, significant brain activity was observed in each test, in specific brain regions, indicating appropriate processing of these stimulations, Monti said.
The scientists conducted three tests to assess Sharon’s level of consciousness. They asked him to imagine he was hitting a tennis ball and to imagine he was walking through the rooms of his home. They also showed him a photograph of a face superimposed on a photo of a house, asking him to focus first on the face and then on the house. The scientists found encouraging, but subtle, signs of consciousness.
"Information from the external world is being transferred to the appropriate parts of Mr. Sharon’s brain. However, the evidence does not as clearly indicate whether Mr. Sharon is consciously perceiving this information," Monti said. "We found faint brain activity indicating that he was complying with the tasks. He may be minimally conscious, but the results were weak and should be interpreted with caution."
Tzvi Ganel, who initiated the project, stressed that Sharon’s family wished to employ these new techniques not only for the benefit of the former prime minister but also for other families in a similar situation.