Spleen may provide new target for treating stroke's debilitating chronic inflammation

September 15, 2015, University of South Florida
Cesario Borlongan, Ph.D., director of the University of South Florida Center of Excellence for Aging and Brain Repair, with postdoctoral fellow Sandra Acosta, Ph.D. USF neuroscientists are conducting pioneering stem cell therapy translational research. Credit: © University of South Florida

Stroke injures the brain, but a new University of South Florida (USF) study indicates an abdominal organ that plays a vital role in immune function, the spleen, may be a target for treating stroke-induced chronic inflammation leading to further brain cell death.

Neuroscientists at the USF Center of Excellence for Aging and Brain Repair found that human bone marrow intravenously administered to post- rats preferentially migrated to the spleen and reduced the inflammatory-plagued secondary cell death associated with stroke progression in the . The study is reported in the September 2015 issue of the American Heart Association journal Stroke.

The USF study helps resolve a perplexing observation by many scientists evaluating the effects of stem cell therapies: Functional recovery occurs in experimental models of neurological disorders, including stroke, despite little or mediocre survival of transplanted stem cells within the injured brain.

"Our findings suggest that even if stem cells do not enter the brain or survive there, as long as the transplanted cells survive in the spleen the anti-inflammatory effects they promote may be sufficient enough to therapeutically benefit the stroke brain," said principal investigator Cesario Borlongan, PhD, professor and director of the USF Center of Excellence for Aging and Brain Repair.

Stroke is a leading cause of death and the number one cause of chronic disability in the United States, yet treatment options are limited. Stem cell therapy has emerged as a potential treatment for ischemic stroke, but most preclinical studies have looked at the effects of stem cells transplanted during - one hour to 3 days after stroke onset.

Following acute stroke, an initial brain attack caused by lack of blood flow, the blood-brain barrier is breeched, allowing the infiltration of inflammatory molecules that trigger secondary in the weeks and months that follow. This acerbated inflammation is the hallmark of chronic stroke.

The USF researchers intravenously administered human bone marrow stem cells to rats 60 days following stroke onset - the chronic stage. The transplanted stem cells were attracted predominantly to the spleen; the researchers found 30-fold more stem cells survived in this peripheral organ than in the brain. Once in the spleen, the stem cells dampened an inflammatory signal (tumor necrosis factor) activated immediately after stroke and prevented the migration from spleen to the compromised brain of harmful macrophages that stimulate inflammation.

This reduced systemic inflammation correlated with significant decreases in the size of lesions caused by acute stroke in the striatum—a portion of the brain controlling movement. There was a trend toward prevention of additional neuron loss in the portion of the brain affecting memory and thinking.

"In the chronic stage of stroke, macrophages are like fuel to the fire of inflammation," Dr. Borlongan said. "So if we can find a way to effectively block the fuel with stem cells, then we may prevent the spread of damage in the brain and ameliorate the disabling symptoms many stroke patients live with."

The USF researchers next plan to test whether transplanting human bone marrow stem cells directly into the spleen will lead to behavioral recovery in post-stroke rats.

The one drug approved for emergency treatment of stroke, the clot-busting drug tPA, must be administered less than 4.5 hours after onset of , and benefits only 3 to 4 percent of patients, Dr. Borlongan said. While more study is needed, evidence from USF and other groups thus far indicates stem cells may help provide a more effective treatment for stroke over a wider timeframe.

"Stem cells are not a magic bullet, but a combination of stem cells and other anti-inflammatory agents may lead to the optimal therapeutic benefit for stroke patients," he said.

Lead study author Sandra Acosta, PhD, a postdoctoral fellow in the USF Department of Neurosurgery and Brain Repair, said targeting the spleen with stem cells or the anti-inflammatory molecules they secrete offers hope for treating chronic neurodegenerative diseases like stroke at later stages.

"We've shown (in an animal model) that it's possible to stop disease progression 60 days after the initial stroke injury, when chronic inflammation in the brain was widespread," she said. "If that can be replicated in humans, it will be powerful."

Explore further: Stem cells aid recovery from stroke

Related Stories

Stem cells aid recovery from stroke

January 27, 2013
Stem cells from bone marrow or fat improve recovery after stroke in rats, finds a study published in BioMed Central's open access journal Stem Cell Research & Therapy. Treatment with stem cells improved the amount of brain ...

Migrating stem cells possible new focus for stroke treatment

May 27, 2014
Two years ago, a new type of stem cell was discovered in the brain that has the capacity to form new cells. The same research group at Lund University in Sweden has now revealed that these stem cells, which are located in ...

Blood-brain barrier repair after stroke may prevent chronic brain deficits

March 25, 2014
Following ischemic stroke, the integrity of the blood-brain barrier (BBB), which prevents harmful substances such as inflammatory molecules from entering the brain, can be impaired in cerebral areas distant from initial ischemic ...

Stem cell-based transplantation approach improves recovery from stroke

June 19, 2014
Stroke is a leading cause of death and disability in developed countries, and there is an urgent need for more clinically effective treatments. A study published by Cell Press June 19th in Stem Cell Reports reveals that simultaneous ...

Bone marrow stem cells show promise in stroke treatment

April 9, 2014
Stem cells culled from bone marrow may prove beneficial in stroke recovery, scientists at UC Irvine's Sue & Bill Gross Stem Cell Research Center have learned.

Scientists make surprising finding in stroke research

March 16, 2015
Scientists at The University of Manchester have made an important new discovery about the brain's immune system that could lead to potential new treatments for stroke and other related conditions.

Recommended for you

To have or not to have... your left atrial appendage closed

May 22, 2018
Each year in the U.S., more than 300,000 people have heart surgery. To reduce risk of stroke for their patients, surgeons often will close the left atrial appendage, which is a small sac in the left side of the heart where ...

Natural antioxidant bilirubin may improve cardiovascular health

May 18, 2018
Bilirubin, a yellow-orange pigment, is formed after the breakdown of red blood cells and is eliminated by the liver. It's not only a sign of a bruise, it may provide cardiovascular benefits, according to a large-scale epidemiology ...

New algorithm more accurately predicts life expectancy after heart failure

May 17, 2018
A new algorithm developed by UCLA researchers more accurately predicts which people will survive heart failure, and for how long, whether or not they receive a heart transplant. The algorithm would allow doctors to make more ...

New genes found that determine how the heart responds to exercise

May 17, 2018
A new study by researchers at Queen Mary University of London and University College London (UCL) has discovered 30 new gene locations that determine how the heart responds to and recovers from exercise.

Novel therapy inhibits complement to preserve neurons and reduce inflammation after stroke

May 16, 2018
A team of investigators at the Medical University of South Carolina (MUSC) has developed a novel therapy for ischemic (clot-caused) stroke and has shown in a preclinical model that it locally inhibits complement at and around ...

Greater burden of atrial fibrillation linked to higher stroke risk

May 16, 2018
Among people with intermittently recurring atrial fibrillation who are not taking anti-blood-clotting medications, those whose hearts were in abnormal rhythms longer were three times more likely to have strokes or other types ...


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.