Blood-brain barrier less permeable in newborns than adults after acute stroke

Results from UCSF study are critical step in developing treatments for newborns who suffer strokes

2012-07-11

(Press-News.org) The ability for substances to pass through the blood-brain barrier is increased after adult stroke, but not after neonatal stroke, according to a new study the UCSF that will be published July 11 in the Journal of Neuroscience.

The novel findings may have major implications for drug development and the treatment of neonatal stroke, the researchers said.

The blood-brain barrier is selectively permeable and blocks unwanted molecules from entering into the brain. The selectivity is achieved through fine coordination in function of many transporting systems in endothelial cells, which line the interior of blood vessels, and communication between endothelial cells and several types of cells in the brain. When blood flow in an artery to the brain is blocked by a blood clot, as occurs in arterial stroke, brain energy metabolism is compromised, and ion and other transporting systems malfunction, leading to blood-brain disruption.

The new finding suggests, the researchers said, that drugs used to treat stroke need to be tailored to the specific makeup of the neonate blood-brain barrier.

"How the blood-brain barrier responds to stroke in adults and neonates currently is poorly understood," said senior author Zinaida Vexler, PhD, director of research at the Neonatal Brain Disorders Center at the Department of Neurology at UCSF.

"The assumption has been that at birth the blood-brain barrier is immature and thus permeable and that a neonatal brain responds in the same way to injury as an adult brain. This would mean that, after a stroke, the blood-brain barrier is an open gate and different molecules could go in and out, like a floodgate," she said. "But in neonatal stroke the situation is very different, and this study shows that the neonatal brain has the ability to protect itself by limiting blood-brain barrier permeability."

In the study, the scientists examined the structural and functional aspects of the blood-brain barrier in live rats that had acute stroke, and found that the blood-brain barrier was markedly more intact in neonatal rats than in adult rats.

The study compared vascular responses to injury in an adult arterial stroke model and an age-appropriate model of neonatal arterial stroke using several blood-brain barrier permeability procedures. Injected molecules that remained in blood vessels under normal conditions leaked into the injured tissue of the adult rats, but the same molecules remained in vessels of neonatal injured rats within 24 hours after injury.

Importantly, the vessels remained intact for molecules of various sizes. The study also showed a different composition of several barrier structural proteins in neonates versus adults, as well as a differential response to stroke at both ages, findings that likely are to contribute to the higher resistance of the neonatal blood-brain barrier after stroke. The study also showed age-related differences in communication between circulating white blood cells and the blood-brain barrier. Neutrophils — a subtype of leukocytes — stuck to injured vasculature and entered the adult brain shortly after stroke, releasing toxic molecules and reactive oxidants and producing damage. In contrast, only a few neutrophils were able to enter the injured neonatal brain. However, pharmacological change – in communication of neutrophils with injured vessels in the neonate made injury worse.

"This study is a very critical step towards developing therapeutics, but these findings are a tip of the iceberg and a lot is still to be learned," said Vexler. "We're moving to characterize the potential for neonatal repair. Some brain damage can't be diagnosed early, but might show up later. Now we are experimenting with postponing certain treatments or tweaking some signaling mechanisms to see if we can enhance the capacity of the immature brain to repair itself."

INFORMATION:

Co-authors of the study are lead author David Fernandez Lopez, PhD, Joel Faustino, BS, Sarah Lee, BS and Nikita Derugin, MA all of the UCSF Department of Neurology, Richard Daneman, PhD, of the UCSF Department of Anatomy, Michael Wendland, PhD, of the UCSF Department of Radiology and Biomedical Imaging and Lu Zhou, BS, of the Stanford University Department of Neurobiology. The authors declare no competing financial interests.

About UCSF Benioff Children's Hospital

UCSF Benioff Children's Hospital creates an environment where children and their families find compassionate care at the forefront of scientific discovery, with more than 150 experts in 50 medical specialties serving patients throughout Northern California and beyond. The hospital admits about 5,000 children each year, including 2,000 babies born in the hospital. For more information, visit http://www.ucsfbenioffchildrens.org/.

About UCSF

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For further information, please visit http://www.ucsf.edu/.

Follow UCSF

UCSF.edu | Facebook.com/ucsf | Twitter.com/ucsf | YouTube.com/ucsf

ELSE PRESS RELEASES FROM THIS DATE:

Moderate drinking may reduce risk of rheumatoid arthritis

2012-07-11

Research: Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study Moderate consumption of alcohol is associated with a reduced risk of developing rheumatoid arthritis, suggests a study published on bmj.com today. The results show that women who regularly consume more than three alcoholic drinks a week for at least 10 years have about half the risk of developing rheumatoid arthritis compared with non-drinkers. After adjusting for factors such as age, smoking and dietary habits, women who reported drinking more than three ...

Weight gain after quitting smoking higher than previously thought

2012-07-11

Research: Weight gain in smokers after quitting cigarettes: meta-analysis Editorial: Quitting smoking and gaining weight: the odd couple Giving up smoking is associated with an average weight gain of 4-5 kg after 12 months, most of which occurs within the first three months of quitting, finds a study published on bmj.com today. Although this figure is higher than previously thought, an accompanying editorial argues that the health benefits of quitting far outweigh this modest gain in body weight and should not deter people from quitting. It is well known that ...

Not all brand-consumer relationships are created equal, says University of Toronto study

2012-07-11

Toronto – Not all brand–consumer relationships are created equal. Marketers who realize this will be in a better position to retain customers and improve the perceptions of consumers who are unhappy with a brand's service or product, says a new paper from the University of Toronto. Consumers form connections with brands in ways that mirror social relationships. How consumers evaluate a brand depends heavily on whether the brand adheres to—or violates—the implicit relationship agreement. Pankaj Aggarwal, a marketing professor at the Rotman School of Management and ...

Preclinical development shows promise to treat hearing loss with Usher syndrome III

2012-07-11

A new study published in the July 11 issue of the Journal of Neuroscience details the development of the first mouse model engineered to carry the most common mutation in Usher syndrome III causative gene (Clarin-1) in North America. Further, the research team from Case Western Reserve University School of Medicine used this new model to understand why mutation in Clarin-1 leads to hearing loss. Usher Syndrome is an incurable genetic disease and it is the most common cause of the dual sensory deficits of deafness and blindness. It affects an estimated 50,000 Americans ...

Researchers develop secure protocol for linking data registries for HPV surveillance

2012-07-11

Ottawa, ON – July 10, 2012 — Monitoring the effectiveness of the HPV vaccine in Canada requires that data from multiple registries and other data sources be combined. Linking registries can be problematic, however, since they are often managed by unrelated organizations. Privacy legislation may also restrict the sharing of data for such linkages. To address these challenges, Dr. Khaled El-Emam and his team at the CHEO Research Institute have developed a secure protocol that allows the linking of individual patient records without revealing personal information, which has ...

Why do low-income couples marry less and divorce more?

2012-07-11

People with lower incomes value the institution of marriage just as much as those with higher incomes and have similar romantic standards for marriage, according to a new study published in the Journal of Marriage and Family. The new research suggests that government initiatives to strengthen marriage among low-income populations should move beyond promoting the value of marriage and instead focus on the actual problems that low-income couples face. The study, which analysed results from a survey of 6,012 people, was carried out by Dr Thomas Trail and Dr Benjamin Karney ...

White LEDs directly on paper

2012-07-11

In his thesis, Gul Amin, who recently received his doctorate at the Physical Electronics and Nanotechnology group, Campus Norrköping, shows how it is possible to grow white LEDs directly on paper and also to print them on wallpaper for example - this method has a patent pending. The active components are nanorods of zinc oxide on a thin layer of polydiethylflourene (PFO), a conducting polymer. But the paper has first been coated with a thin, water-repellent, protective and levelling layer of cyclotene, a resin. "This is the first time anyone has been able to build ...

Melanoma-promoting gene discovered

2012-07-11

This press release is available in German. Black skin cancer, also known as melanoma, is particularly aggressive and becoming increasingly common in Switzerland. Despite intensive research, however, there is still no treatment. Researchers from the University of Zurich have now discovered a gene that plays a central role in black skin cancer. Suppressing this gene in mice inhibits the development of melanoma and its proliferation – a discovery that could pave the way for new forms of therapy. Until recently, it was assumed that a tumor was composed of many ...

The magnetic sense

2012-07-11

Migratory birds and fish use the Earth's magnetic field to find their way. LMU researchers have now identified cells with internal compass needles for the perception of the field – and can explain why high-tension cables perturb the magnetic orientation. Although many animal species can sense the geomagnetic field and exploit it for spatial orientation, efforts to pinpoint the cells that detect the field and convert the information into nerve impulses have so far failed. "The field penetrates the whole organism, so such cells could be located almost anywhere, making them ...

Rare glimpse into the origin of species

2012-07-11

A new species of monkey flower, created by the union of two foreign plant species, has been discovered on the bank of a stream in Scotland. Genetic changes in this attractive yellow-flowered hybrid have allowed it to overcome infertility and made it a rare example of a brand new species that has originated in the wild in the last 150 years. Thousands of wild species and some crops are thought to have originated in this way, yet only a handful of examples exist where this type of species formation has occurred in recent history. The ancestors of the new plant were brought ...

Blood-brain barrier less permeable in newborns than adults after acute stroke

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: