Researchers find far-reaching, microvascular damage in uninjured side of brain after stroke

May 20, 2013

While the effects of acute stroke have been widely studied, brain damage during the subacute phase of stroke has been a neglected area of research. Now, a new study by the University of South Florida reports that within a week of a stroke caused by a blood clot in one side of the brain, the opposite side of the brain shows signs of microvascular injury.

is a leading cause of death and disability in the United States, and increases the risk for dementia.

"Approximately 80 percent of strokes are ischemic strokes, in which the blood supply to the brain is restricted, causing a shortage of oxygen," said study lead author Svitlana Garbuzova-Davis, PhD, associate professor in the USF Department of Neurosurgery and Brain Repair. "Minutes after , there are serious effects within the brain at both the molecular and cellular levels. One understudied aspect has been the effect of ischemic stroke on the competence of the blood-brain barrier and subsequent related events in remote ."

Using a , researchers at USF Health investigated the subacute phase of ischemic stroke and found deficits in the microvascular integrity in the brain hemisphere opposite to where the initial stroke injury occured.

The study was published in the May 10, 2013 issue of PLOS One.

The USF team found that "diachisis," a term used to describe certain brain deficits remote from primary insult, can occur during the subacute phase of ischemic stroke. The research discovered diachisis is closely related to a breakdown of the blood-brain barrier, which separates circulating blood from .

In the subacute phase of an ischemic stroke, when the stroke-induced disturbances in the brain occur in remote brain microvessels, several areas of the brain are affected by a variety of injuries, including neuronal swelling and diminished in brain structures. The researchers suggest that recognizing the significance of microvascular damage could make the blood-brain barrier (BBB) a therapeutic "target" for future neuroprotective strategies for stroke patients.

The mechanisms of BBB permeability at different phases of stroke are poorly understood. While there have been investigations of BBB integrity and processes in ischemic stroke, the researchers said, most examinations have been limited to the phase immediately after stroke, known as . Their interest was in determining microvascular integrity in the brain hemisphere opposite to an initial stroke injury at the subacute phase.

Accordingly, this study using rats with surgically-simulated strokes was designed to investigate the effect of ischemic stroke on the BBB in the subacute phase, and the effects of a compromised BBB upon various brain regions, some distant from the stroke site.

"The aim of this study was to characterize subacute diachisis in rats modeled with ischemic stroke," said co-author Cesar Borlongan, PhD, professor and vice chairman for research in the Department of Neurosurgery and Brain Repair and director of the USF Center for Aging and Brain Repair. "Our specific focus was on analyzing the condition of the BBB and the processes in the areas of the brain not directly affected by ischemia. BBB competence in subacute diachisis is uncertain and needed to be studied."

Their findings suggest that damage to the BBB, and subsequent vascular leakage as the BBB becomes more permeable, plays a major role in subacute diachisis.

The increasing BBB permeability hours after the simulated stroke, and finding that the BBB "remained open" seven days post-stroke, were significant findings, said Dr. Garbuzova-Davis, who is also a researcher in USF Center for Aging and . "Since increased BBB permeability is often associated with brain swelling, BBB leakage may be a serious and life-threatening complication of ischemic stroke."

Another significant aspect was the finding that autophagy—a mechanism involving cell degradation of unnecessary or dysfunctional cellular components —plays a role in the subacute phase of ischemia. Study results showed that accumulation of numerous autophagosomes within endothelial cells in microvessels of both initially damaged and non-injured areas might be closely associated with BBB damage.

Autophagy is a complex but normal process usually aimed at "self-removing" damaged cell components to promote cell survival. It was unclear, however, whether the role of autophagy in subacute post-ischemia was promoting cell survival or cell death.

More than 30 percent of patients who survive strokes develop dementia within two years, the researchers noted.

"Although dementia is complex, vascular damage in post-stroke patients is a significant risk factor, depending on the severity, volume and site of the stroke," said study co-author Dr. Paul Sanberg, USF senior vice president for research and innovation. "Ischemic stroke might initiate neurodegenerative dementia, particularly in the aging population."

The researchers conclude that repair of the BBB following ischemic stroke could potentially prevent further degradation of surviving neurons.

"Recognizing that the BBB is a therapeutic target is important for developing neuroprotective strategies," they said.

Explore further: Breaking through the blood-brain barrier

Related Stories

Breaking through the blood-brain barrier

May 13, 2013
To mark the European Month of the Brain, we look at one EU-funded project that has focussed efforts on drug delivery across the so-called blood-brain barrier. The blood-brain barrier (BBB), while preforming a key protective ...

Astrocyte signaling sheds light on stroke research

March 18, 2013
New research published in The Journal of Neuroscience suggests that modifying signals sent by astrocytes, our star-shaped brain cells, may help to limit the spread of damage after an ischemic brain stroke. The study in mice, ...

Do-it-yourself brain repair following stroke

July 11, 2011
Stroke is a leading cause of long-term disability and death in the United States. A team of researchers — led by Gregory Bix, at Texas A&M College of Medicine, College Station — has identified a way to exploit one ...

Research opens up possibility of therapies to restore blood-brain barrier

January 2, 2013
(Medical Xpress)—Research led by Queen Mary, University of London, has opened up the possibility that drug therapies may one day be able to restore the integrity of the blood-brain barrier, potentially slowing or even reversing ...

Chronic pain common complication of clot-caused strokes

April 4, 2013
Chronic or persistent pain is a common—and likely under-recognized—complication of ischemic strokes (caused by a blocked blood vessel) according to new research in the American Heart Association journal Stroke.

Therapeutic time window important factor for cord blood cell transplantation after stoke

October 1, 2012
A research team from Germany has found that optimal benefit and functional improvement for ischemic stroke results when human umbilical cord blood mononuclear cells (hUCB MNCs) are transplanted into rat stroke models within ...

Recommended for you

The neural codes for body movements

July 21, 2017
A small patch of neurons in the brain can encode the movements of many body parts, according to researchers in the laboratory of Caltech's Richard Andersen, James G. Boswell Professor of Neuroscience, Tianqiao and Chrissy ...

Faulty support cells disrupt communication in brains of people with schizophrenia

July 20, 2017
New research has identified the culprit behind the wiring problems in the brains of people with schizophrenia. When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia ...

Scientists reveal how patterns of brain activity direct specific body movements

July 20, 2017
New research by Columbia scientists offers fresh insight into how the brain tells the body to move, from simple behaviors like walking, to trained movements that may take years to master. The discovery in mice advances knowledge ...

Scientists discover combined sensory map for heat, humidity in fly brain

July 20, 2017
Northwestern University neuroscientists now can visualize how fruit flies sense and process humidity and temperature together through a "sensory map" within their brains, according to new research.

Team traces masculinization in mice to estrogen receptor in inhibitory neurons

July 20, 2017
Researchers at Cold Spring Harbor Laboratory (CSHL) have opened a black box in the brain whose contents explain one of the remarkable yet mysterious facts of life.

Speech language therapy delivered through the Internet leads to similar improvements as in-person treatment

July 20, 2017
Telerehabilitation helps healthcare professionals reach more patients in need, but some worry it doesn't offer the same quality of care as in-person treatment. This isn't the case, according to recent research by Baycrest.

0 comments

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.