Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune cells may heal bleeding brain after strokes

21.09.2017

NIH-funded preclinical rodent study points to neutrophils for potential treatment options

While immune cells called neutrophils are known to act as infantry in the body's war on germs, a National Institutes of Health-funded study suggests they can act as medics as well. By studying rodents, researchers showed that instead of attacking germs, some neutrophils may help heal the brain after an intracerebral hemorrhage, a form of stroke caused by ruptured blood vessels. The study suggests that two neutrophil-related proteins may play critical roles in protecting the brain from stroke-induced damage and could be used as treatments for intracerebral hemorrhage.


Researchers studied how immune cells called neutrophils may help protect the brain from damage caused by intracerebral hemorrhagic stroke.

Courtesy of Aronowski lab, University of Texas Health Science Center, Houston

"Intracerebral hemorrhage is a damaging and often fatal form of stroke for which there are no effective medicines," said Jaroslaw Aronowski, M.D., Ph.D., professor, department of neurology, at the University of Texas Health Science Center at Houston, and senior author of the study published in Nature Communications. "Our results are a hopeful first step towards developing a treatment for this devastating form of stroke."

Accounting for 10 to 15 percent of all strokes, intracerebral hemorrhages happen when blood vessels rupture and leak blood into the brain, often leading to death or long-term disability. Chronic high blood pressure is the leading risk factor for these types of strokes. The initial phase of damage appears to be caused by the pressure of blood leaking into the brain. Over time, further damage may be caused by the accumulation of toxic levels of blood products, infiltrating immune cells, and swelling.

Decades of research suggest that neutrophils are some of the earliest immune cells to respond to a hemorrhage, and that they may both harm and heal the brain. In this study, the researchers found that interleukin-27 (IL-27), a protein that controls the activity of immune cells, may shift the role of neutrophils from harming the brain to helping with recovery.

Injections of IL-27 after a hemorrhage helped mice recover. Days after the strokes, the treated mice had better mobility, including walking, limb stretching and navigating holes in a floor. In contrast, injections of an antibody that blocked natural IL-27 activity slowed recovery. The brains of the mice treated with IL-27 also showed less damage. They had less swelling around the hemorrhages and lower levels of iron and the blood protein hemoglobin, both of which are toxic at high levels.

"This study shines a spotlight on the critical role the immune system may play in helping the brain heal after a hemorrhage or stroke and opens new avenues for stroke treatment strategies," said Jim Koenig, Ph.D., program director at the NIH's National Institute of Neurological Disorders and Stroke.

Neutrophils are born in bone marrow and carry chemicals in hundreds of densely filled packets called granules, which look like dark spots under a microscope. Typically, when the body senses bacteria or an injury, neutrophils rush to the invasion site and release germ killing chemicals from the granules. This appears to happen minutes after a hemorrhagic stroke.

In this study, the researchers suggested that after a hemorrhagic stroke the brain secretes high levels of IL-27, which leads to a second wave of neutrophils arriving with granules filled with higher amounts of healing molecules. IL-27 levels were elevated in the brain and blood of the mice an hour after hemorrhages and stayed high for three days, peaking at 24 hours later. Further experiments suggested that brain cells called microglia produced the IL-27 in response to the presence of red blood cells.

Once released, IL-27 molecules appeared to travel to the bones of the mice, infiltrated the marrow, and changed the role newborn neutrophils played in response to a stroke. When the researchers extracted newborn neutrophils from the bones of mice and treated them with IL-27, the chemical raised the activity of genes associated with healing, especially lactoferrin, while reducing the activity of genes associated with killing cells. Conversely, treating mice with an IL-27 neutralizing antibody after a hemorrhage lowered lactoferrin gene activity.

"Our results suggested that IL-27 links the brain to the bones," said Dr. Aronowski. "We can use these results as a source for ideas for developing potential treatments for hemorrhagic stroke."

Finally, the researchers showed the iron binding protein lactoferrin may protect the brain from intracerebral hemorrhagic strokes. Mice and rats injected with lactoferrin 30 minutes after hemorrhages recovered faster and had reduced brain damage as compared to animals given placebos. In one set of experiments, the researchers found that giving mice lactoferrin 24 hours after a stroke was also effective.

"Lactoferrin appears to have a long treatment window," said Dr. Aronowski. "This means lactoferrin might one day be used to help patients recover from intracerebral hemorrhage."

Dr. Aronowski's team is taking the next steps towards testing lactoferrin treatment in patients.

###

Article:

Zhao et al. Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage. Nature Communications, August 19, 2017: 10.1038/s41467-017-00770-7

This study was supported by grants from NINDS (NS096308, NS090650)

For more information: http://www.ninds.nih.gov http://www.ninds.nih.gov/Disorders/All-Disorders/Stroke-Information-Page stroke.nih.gov/materials/needtoknow.htm http://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Stroke-Hope-Through-Research

NINDS is the nation's leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Media Contact

Christopher G. Thomas
nindspressteam@ninds.nih.gov
301-496-5751

 @NINDSnews

http://www.ninds.nih.gov 

Christopher G. Thomas | EurekAlert!

More articles from Life Sciences:

nachricht Blood test shows promise for early detection of severe lung-transplant rejection
23.01.2019 | NIH/National Heart, Lung and Blood Institute

nachricht Evolution of signaling molecules opens door to new sepsis therapy approaches
23.01.2019 | Technische Universität München

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Bifacial Stem Cells Produce Wood and Bast

Heidelberg researchers study one of the most important growth processes on Earth

So-called bifacial stem cells are responsible for one of the most critical growth processes on Earth – the formation of wood.

Im Focus: Energizing the immune system to eat cancer

Abramson Cancer Center study identifies method of priming macrophages to boost anti-tumor response

Immune cells called macrophages are supposed to serve and protect, but cancer has found ways to put them to sleep. Now researchers at the Abramson Cancer...

Im Focus: Ten-year anniversary of the Neumayer Station III

The scientific and political community alike stress the importance of German Antarctic research

Joint Press Release from the BMBF and AWI

The Antarctic is a frigid continent south of the Antarctic Circle, where researchers are the only inhabitants. Despite the hostile conditions, here the Alfred...

Im Focus: Ultra ultrasound to transform new tech

World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles

The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.

Im Focus: Flying Optical Cats for Quantum Communication

Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.

In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

 
Latest News

Graphene and related materials safety: human health and the environment

23.01.2019 | Materials Sciences

Blood test shows promise for early detection of severe lung-transplant rejection

23.01.2019 | Life Sciences

Evolution of signaling molecules opens door to new sepsis therapy approaches

23.01.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>