Novel basic science news tip sheet

Leakier guts may be why older people are more likely to die or have a poor recovery after clot-caused strokes, according to a study in mice presented at the American Stroke Association's International Stroke Conference 2015.

Researchers found that molecules and bacteria cross the intestinal walls in both aged mice (18-20 months) and young ones (8-12 weeks) after stroke, but only the young were able to clear bacterial infection and resolve inflammation.

After an experimentally induced stroke, with the middle cerebral artery blocked for 90 minutes and then reopened, aged mice had 200 times more bacteria in their abdominal lymph nodes than younger mice, and more frequently tested positive for infection in other extraintestinal organs.

Interleukin-6, a substance produced by the immune system in response to injury or infection and a marker of sepsis (a life-threatening inflammatory response to infection), increased in all mice after stroke but remained elevated in the aged mice that were 50 percent more likely to die within seven days. This suggests that the high mortality in aged mice after stroke is related to exacerbation of intestinal permeability, bacteria getting out of the gut and subsequent induction of sepsis.

Therapies targeting the gut to reduce intestinal permeability may lower the severity of inflammation and improve the prognosis of aged stroke patients, researchers said.

Joshua Crapser, B.S., University of Connecticut Health Center, Farmington, Conneticut.

Note: Actual presentation is 5:30 p.m. CT, Wednesday, Feb. 11, 2015.

Housing aged mice in pairs enhances their recovery after stroke, according to a study presented at the American Stroke Association's International Stroke Conference 2015.

Social isolation slows functional recovery and worsens cell damage after stroke in young animals, primarily by increasing the body's inflammatory response. Changes occur in the inflammatory response with age, so it was unknown if isolation would induce the same detrimental effects in aged mice. Researchers examined whether social isolation interfered with short- or long-term recovery in aged male mice and whether being housed in pairs would reverse those effects.

Male 18-month-old mice were pair-housed for two weeks before undergoing an experimentally induced stroke (middle cerebral artery was occluded for 60 minutes) or a sham surgery with no cut-off in circulation to the brain. Afterwards, the animals were housed alone or in pairs.

After 72 hours, mice isolated after stroke had larger volume of dead brain tissue and more severe neurological impairment than those housed in pairs. Levels of interleukin 6, an inflammatory substance produced in response to injury, were higher in mice isolated after a stroke compared with pair-housed mice that had stroke or sham surgery; levels were similar by four weeks post-stroke.

Paired animals performed better than isolated mice on an object recognition test and had greater expression of a growth factor that promotes cell proliferation and reduces inflammation after stroke (brain-derived neurotrophic factor), and had higher levels of brain white matter protein (myelin basic protein).

Rajkumar Verma, Ph.D., University of Connecticut Health Center, Farmington, Conneticut.

Note: Actual presentation is 5:20 p.m. CT, Wednesday, Feb. 11, 2015.

Stem cell injections into the brain may improve some cognitive functions in people who haven't recovered months or years after a clot-caused stroke, according to a study presented at the American Stroke Association's International Stroke Conference 2015.

In a preliminary study, 18 patients who had sustained moderate or severe ischemic strokes and remained paralyzed on one side six to 60 months later (average 22 months) received stem cell injections. Patients received 2.5, 5 or 10 million adult bone marrow cells engineered to secrete factors previously shown to protect neurons in animal models.

In tests performed six and 12 months after the injections, some patients showed improvement in some verbal learning tasks. Results differed depending on the location of the stroke. These results should prompt further investigations of cognitive function in studies of stem cell therapy for stroke recovery, researchers said.

Cynthia Kenmuir, M.D., Ph.D., University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;

Note: Actual presentation is 9:45 a.m. CT, Wednesday, Feb. 11, 2015.

Supplementing a natural substance that protects nerve cells and encourages new blood vessel formation may aid in new neural growth after stroke when started a week later, according to a mouse study presented at the American Stroke Association's International Stroke Conference 2015.

Currently, the only FDA-approved drug, tPA, which dissolves clots to restore blood flow, must be given within hours after stroke.

Previously, researchers found that after an experimentally induced stroke (with temporary or permanent blockage of the middle cerebral artery), functional outcomes in rodents improved if they received the bioactive protein fragment perlecan domain V (DV) within six-24 hours.

In the new study, 3-month-old mice received DV or an inactive substance seven days after stroke and every three days thereafter. After 21 days, more new neurons had reached the area of brain damage and survived in mice receiving DV.

Aileen Marcelo-McCabe, Ph.D., University of Kentucky, Lexington, Kentucky;

Note: Actual presentation is 1:42 p.m. CT, Thursday, Feb. 12, 2015.

The spleen -- not the brain -- may be the key target in successful cell therapy after a stroke, according to a study in mice presented at the American Stroke Association's International Stroke Conference 2015.

After a stroke, the spleen seems to contribute to ongoing inflammation and brain damage.

Researchers compared the outcome of stroke and cell therapy with autologous bone marrow mononuclear cells (MNCs) in mice with intact spleens and those with spleens removed two weeks before an experimentally induced stroke. After stroke, the size of brain injury was smaller and neurological problems were less severe in mice without spleens. MNCs treatment improved functional recovery in mice with spleens but was no better than a placebo in mice without spleens.

Bing Yang, M.D., University of Texas Medical School at Houston, TX.

Note: Actual presentation is 6 p.m. CT, Thursday, Feb. 12, 2015.

###

Additional Resources:

Downloadable animation and images related to this news release are on the right column of the news tips link http://newsroom.heart.org/news/novel-basic-science-news-tip-sheet?preview=f78ccf3ec3ed7ed824e5f3fd52f6d99b.

Follow news from ASA International Stroke Conference 2015 on @HeartNews #ISC15.

Statements and conclusions of study authors that are presented at American Stroke Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The association makes no representation or warranty as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at http://www.heart.org/corporatefunding.

Life is why we fund scientific breakthroughs that save and improve lives.