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Post-stroke delivery of neurotrophic factor MANF promotes functional recovery in rats

Post-stroke delivery of neurotrophic factor MANF promotes functional recovery in rats

First appeared on ScienceDaily.com

Stroke is the most common cause of adult disability. This is due not only to the high incidence of stroke, but also because spontaneous recovery is often incomplete and no drugs are available that hasten recovery.

Mesencephalic astrocyte-derived neurotrophic factor MANF is neuroprotective when administered before experimental stroke in rats.

A massive immune response mediated by activated microglia and macrophages occurs in the rat brain tissue after stroke. MANF has also recently been shown to recruit immune cells to the eye after retinal damage and to mediate retinal repair after photoreceptor transplantation.

Dr. Mikko Airavaara and his group at the University of Helsinki, Institute of Biotechnology administered MANF to rats after the ischemic brain injury, either by injecting recombinant MANF protein or by delivering a MANF-expressing viral vector into the brain area adjacent to the lesion.

When MANF was administered directly into brain tissue 2 to 3 days after stroke, it did not affect lesion volume but promoted reversal of stroke-induced behavioural impairments. “This indicated that MANF had an effect on the recovery of brain tissue function after injury,” says Dr. Kert Mätlik, the lead author of the study.

MANF treatment transiently increased the number of phagocytic macrophages close to the ischemic lesion. These cells are the professional cleaning crew that clears dying cells and dead material from injured tissue. “This really got me wondering if some of the inflammation is beneficial. What if facilitating specific branches of the inflammatory response enhances both tissue repair and functional recovery?” asks Mikko Airavaara.

By virtue of the presence of a skilled neurosurgeon, Dr. Kuan-Yin Tseng in the lab and a collaboration with Dr. Maria Lindahl, the researchers were also able to study the outcome of experimental stroke in mice that lack MANF in their brain cells. These additional experiments revealed the neuroprotective effect of endogenously-produced MANF against ischemic injury.

Mikko Airavaara has found the results very encouraging for pursuing the ultimate goal of combating long-term disability in stroke patients: “All in all this is a proof-of-concept study that shows the beneficial effect of MANF treatment on the reversal of stroke-induced behavioural deficits. It suggests that MANF or therapeutic agents with similar activity could be developed to repair brain tissue after stroke. However, much more work is needed before clinical studies can be considered.”

Story Source: University of Helsinki. “Post-stroke delivery of neurotrophic factor MANF promotes functional recovery in rats.” ScienceDaily. ScienceDaily, 11 June 2018. <www.sciencedaily.com/releases/2018/06/180611133731.htm>.

A deeper understanding of AFib could lower risk

A deeper understanding of AFib could lower risk

First appeared on ScienceDaily.com

More than 2.5 million Americans are living with Atrial Fibrillation (AFib). AFib is an irregular heartbeat that can lead to blood clots, stroke, heart failure and other heart-related complications.

What doctors and researchers currently understand about treating AFib stems mainly from whether a patient has been diagnosed with the condition or not. University of Minnesota researchers are urging the medical community to take a closer look, specifically at AFib burden.

AFib burden refers to the amount of AFib that an individual has. The goal of the scientific statement published in the American Heart Association’s journal Circulation is to increase knowledge and awareness by healthcare professionals of effective, state-of-the-art science related to the causes, prevention, detection, management, and future research needs related to AFib burden.

“We hope to bring awareness to this concept of measuring the AFib burden and then to outline what we know about it,” said Lin Yee Chen, MD, MS, tenured associate professor, Department of Medicine at the University of Minnesota Medical School, “the hope then is to use that knowledge so more research can be done to fill in those gaps.”

AFib is associated with an elevated risk of stroke, and this statement also pushes for more research to refine risk classifications for stroke. Further understanding the relationship between AFib pattern or burden and stroke risk might result in deeper insights into stroke prevention.

“We could see an enormous benefit to our patient population once these standards are applied. And now is the time to do so,” said Chen.

Story Source: University of Minnesota Medical School. “A deeper understanding of AFib could lower risk.” ScienceDaily. ScienceDaily, 6 June 2018. <www.sciencedaily.com/releases/2018/06/180606143719.htm>.

Electrophysiological sign of cerebral infarction identified

Electrophysiological sign of cerebral infarction identified

A massive and extremely slow change in electrical potential is evidence of irreparable damage

First appeared on ScienceDaily.com

Researchers from Charité — Universitätsmedizin Berlin have analyzed the underlying electrophysiological indicators of subarachnoid hemorrhage, the second most common type of brain hemorrhage that can lead to ischemic stroke within a matter of days. Their findings, which have been published in the journal Brain, may lay the foundations for new stroke treatments.

Subarachnoid hemorrhage is a type of brain bleed that occurs in the area between the membranes surrounding the brain. Patients with subarachnoid hemorrhage can develop complications within approximately one week. Between one in three and one in four patients will develop symptoms of ischemic stroke, a type of stroke caused by an inadequate blood supply. This phenomenon occurs as the result of mechanisms triggered by the molecular breakdown products of the patient’s earlier hemorrhagic stroke. It sets off a wave of electrochemical depolarization, or ‘spreading depolarization’, within the brain tissue. Affected areas of the brain require large amounts of energy in order to restore normal conditions.

In healthy brains, this depolarization of nerve cells is linked to blood supply, meaning blood vessels widen in areas of the brain that are active. However, a subarachnoid hemorrhage may disrupt the signaling cascades between nerve cells and blood vessels, so that the depolarization of nerve cells causes extreme constriction of the blood vessels, which leads to spreading ischemia. Deprived of energy, the nerve cells are incapable of restoring normal electrochemical gradients. If depolarization persists for too long, affected nerve cells will begin to die off. Measurements of the electrical brain potential will then show an extreme and very gradual change , a process known as ‘negative ultraslow potential’, which is indicative of ‘terminal spreading depolarization’.

“Two months ago, we were able to show for the first time that terminal spreading polarization occurs in humans — namely in patients who had suffered cardiac arrest. Now we have been able to show that it also occurs in patients with cerebral infarctions after subarachnoid hemorrhage,” explains Prof. Dr. Jens Dreier of Charité’s Center for Stroke Research Berlin (CSB). Prof. Dreier and his team analyzed data from 11 patients, comparing their findings with results obtained from animal experiments. The waves of depolarization observed indicate disturbances of energy metabolism. The ‘negative ultraslow potential’ constitutes the electrophysiological correlate of infarction, and of tissue death due to an inadequate supply of blood.

Prof. Dreier emphasizes: “Measurements of spreading depolarization may prove as important to the development of interventions for patients with stroke, global ischemia and traumatic brain injury, as similar electrophysiological tools have proved in the past, in the areas of epilepsy or cardiology — because they make the underlying causes visible.”

Story Source: Charité – Universitätsmedizin Berlin. “Electrophysiological sign of cerebral infarction identified: A massive and extremely slow change in electrical potential is evidence of irreparable damage.” ScienceDaily. ScienceDaily, 29 May 2018. <www.sciencedaily.com/releases/2018/05/180529132142.htm>.

Mice regrow brain tissue after stroke with bioengineered gel

Mice regrow brain tissue after stroke with bioengineered gel

Replacement neurons, blood vessels fill in stroke cavity; gel provides scaffolding

First appeared on ScienceDaily.com

In a first-of-its-kind finding, a new stroke-healing gel helped regrow neurons and blood vessels in mice with stroke-damaged brains, UCLA researchers report in the May 21 issue of Nature Materials.

“We tested this in laboratory mice to determine if it would repair the brain in a model of stroke, and lead to recovery,” said Dr. S. Thomas Carmichael, Professor and Chair of neurology at UCLA. “This study indicated that new brain tissue can be regenerated in what was previously just an inactive brain scar after stroke.”

The results suggest that such an approach may someday be a new therapy for stroke in people, said Dr. Tatiana Segura, a former Professor of Chemical and Biomolecular Engineering at UCLA who is now a professor at Duke University. Carmichael and Segura collaborated on the study.

The brain has a limited capacity for recovery after stroke and other diseases. Unlike some other organs in the body, such as the liver or skin, the brain does not regenerate new connections, blood vessels or new tissue structures. Tissue that dies in the brain from stroke is absorbed, leaving a cavity, devoid of blood vessels, neurons or axons, the thin nerve fibers that project from neurons.

To see if healthy tissue surrounding the cavity could be coaxed into healing the stroke injury, Segura engineered a gel to inject into the stroke cavity that thickens to mimic the properties of brain tissue, creating a scaffolding for new growth.

The gel is infused with molecules that stimulate blood vessel growth and suppress inflammation, since inflammation results in scars and impedes regrowth of functional tissue.

After 16 weeks, stroke cavities in mice contained regenerated brain tissue, including new neural networks — a result that had not been seen before. The mice with new neurons showed improved motor behavior, though the exact mechanism wasn’t clear.

“The new axons could actually be working,” said Segura. “Or the new tissue could be improving the performance of the surrounding, unharmed brain tissue.”

The gel was eventually absorbed by the body, leaving behind only new tissue.

This research was designed to explore recovery in acute stroke, or the period immediately following stroke — in mice, that is five days; in humans, that is two months. Next, Carmichael and Segura are determining if brain tissue can be regenerated in mice long after the stroke injury. More than 6 million Americans are living with the long-term outcomes of stroke, known as chronic stroke.

Story Source: University of California – Los Angeles. “Mice regrow brain tissue after stroke with bioengineered gel: Replacement neurons, blood vessels fill in stroke cavity; gel provides scaffolding.” ScienceDaily. ScienceDaily, 21 May 2018. <www.sciencedaily.com/releases/2018/05/180521131811.htm>.

Imaging may allow safe tPA treatment of patients with unwitnessed strokes

Imaging may allow safe tPA treatment of patients with unwitnessed strokes

First published on ScienceDaily.com

A study led by Massachusetts General Hospital (MGH) investigators may lead to a significant expansion in the number of stroke patients who can safely be treated with intravenous tPA (tissue plasminogen activator), the “clot busting” drug that has greatly reduced stroke-related disability and deaths in eligible patients. The report, published online in Annals of Neurology, describes the results of a trial using MR-based imaging technologies to identify patients likely to be within 4.5 hours of stroke onset, even though their initial symptoms had not been witnessed. (more…)

Imaging may allow safe tPA treatment of patients with unwitnessed strokes

Dementia trend shows later onset with fewer years of the disease

First published on ScienceDaily.com

The diagnosis is one that a family never wants to hear: Your father has Alzheimer’s disease. Your mother has stroke-related dementia.

A recently released study, included in a special supplement to the Journal of Gerontology, indicates that dementia’s impact might be compressing a bit. That is, people might be developing dementia later and living with it for a shorter period of time. (more…)