How adult stem cell therapy reduces inflammatory damage

ScienceDaily (Feb. 14, 2011) — Medical researchers from The University of Texas Health Science Center at Houston (UTHealth) presented new research results at the American Heart Association International Stroke Conference that demonstrated how MultiStem®, a novel stem cell therapy being developed by Athersys, Inc. provided multiple benefits when administered in preclinical models of ischemic stroke. The study, conducted by leading researchers from the Department of Neurology at the UTHealth Medical School working in collaboration with scientists at Athersys, illustrated the potential benefits of MultiStem therapy for treating stroke. Researchers observed that intravenous administration of MultiStem one day after a stroke reduced inflammatory damage in the brain and resulted in a significant improvement in motor skills.

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"We are seeing a paradigm shift in the way some types of stem cells may enhance recovery from stroke," said Sean I. Savitz, M.D., principal investigator and associate professor of neurology at UTHealth. "The stem cells may actually exert some of their effects on other organs such as the spleen. The spleen seems to play an important role in some neurological disorders by contributing, for example, to ongoing inflammation and brain injury after stroke. We're finding these stem cells are working on dampening inflammation involving the spleen."

According to the American Heart Association, approximately 800,000 individuals suffer a stroke each year in the United States, and an estimated 2 million individuals suffer a stroke each year in the U.S., Japan, and major European countries combined. Approximately 85% of strokes are ischemic, meaning they are caused by a blockage of blood flow in the brain, which occurs as a result of a clot or "thrombus." Currently there is only one FDA-approved drug therapy for the treatment of ischemic stroke, the thrombolytic tPA, which helps to dissolve the flow-impeding blood clot. However, tPA must be administered within several hours from when the stroke has occurred in order to be effective. Due to its limited window, only about 5% of all patients who could potentially benefit from therapy with tPA actually receive treatment. Given the lack of effective therapies, many patients who suffer a stroke require extensive physical therapy or experience significant or permanent disability, and as a result, must receive long-term institutional care or be cared for by a family member. As a consequence of an aging population, recent forecasts from the American Heart Association project that the prevalence of stroke will increase by 25% in the next 20 years, and the total estimated annual cost for treating and caring for stroke survivors will skyrocket from $64 billion in 2010 to $140 billion in 2030, representing a substantial increase in cost to the national healthcare system.

In the rat model of stroke used in the study, animals that received treatment with MultiStem showed statistically significant improvement in motor skills relative to animals that received placebo, and also showed reduced cell death, reduction of inflammatory cytokines and an increase in anti-inflammatory cytokines. Interestingly, researchers found that animals treated with placebo showed a reduction in spleen size and an increase in inflammatory cytokines in the blood, whereas animals that were treated with MultiStem showed normal spleen size and increased levels of anti-inflammatory cytokines in the blood. The spleen is believed to play a significant role in promoting and sustaining the inflammation that can result in substantial long-term damage following brain injury.

"Ischemic stroke represents an enormous clinical, economic and social burden that is expected to increase dramatically in the years ahead as a result of an aging population, and the corresponding increase in the number of individuals that are susceptible to all forms of cardiovascular disease," said Gil Van Bokkelen, Chairman and Chief Executive Officer of Athersys. "MultiStem appears to have profound effects in multiple neurological injury models, by reducing inflammation, protecting at-risk brain tissue, and promoting tissue repair. If we can develop new, more effective therapies that meaningfully extend the treatment window for stroke victims, we can improve clinical care, reduce long-term health care costs, and improve the quality of life for millions of people."

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Swedish discovery could lead to new stroke therapy

ScienceDaily (Feb. 18, 2011) — The opportunities to treat a stroke have long been limited to the hours after an attack. The loss of brain function caused by the stroke has previously been regarded as permanent. Brain researchers at Lund University have now discovered a substance that opens up the possibility of treatment up to two days after a stroke.

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The only acute treatment for a stroke currently available is thrombolysis. This uses drugs that dissolve the blood clot responsible for the stroke, but it only reaches around 10 per cent of stroke patients in time to prevent lasting damage. For other patients, there are no other effective drugs that reduce the loss of brain function following a stroke.

Researchers at the Laboratory for Experimental Brain Research in Lund, together with American researchers, have discovered a substance that reinforces the brain's self-healing functions after a stroke. It has long been known that people affected by a stroke can regain some lost function during the first six months. Professor Tadeusz Wieloch and his colleagues have found a way to activate a protein in the brain, the sigma-1 receptor, which plays an important role in the brain's recovery during the critical period after the injury.

The study, which is published in the scientific journal Brain, began with experiments on rats. The animals were subjected to a stroke and then placed in different environments -- an enriched cage with extra stimulation in the form of several levels of tubes, beams and ladders, and a normal cage.

"After performing a genetic analysis of the rats that stayed in the normal cage and those that were in an enriched cage, we found that many genes were activated by the enriched environment. One of these genes coded for the protein sigma-1 receptor. We then injected the rats with a specific substance that activated the sigma-1 receptor and found that the rats regained their function more quickly than the untreated animals," explains Professor Wieloch.

The idea is to recreate and reinforce the brain's natural response to an enriched environment. By injecting the activating substance, brain repair is stimulated. This result of Swedish basic research, which started over 15 years ago, has led to a clinical trial on stroke patients by a Japanese pharmaceutical company.

"We are very pleased that our research on stroke here in Lund has made it all the way from our experiments in the lab to an international clinical trial," says Professor Wieloch.

"This is an excellent example of how basic research can be translated into a healthcare setting and possibly lead to new and better therapies. It also exemplifies the fact that, within medical research, it is a long journey from experimental studies to results that benefit the patient," says Professor Wieloch.

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Self-administered light therapy may improve cognitive function after traumatic brain injury

ScienceDaily (Mar. 18, 2011) — At-home, daily application of light therapy via light-emitting diodes (LEDs) placed on the forehead and scalp led to improvements in cognitive function and post-traumatic stress disorder in patients with a traumatic brain injury (TBI), according to a groundbreaking study published in Photomedicine and Laser Surgery, a peer-reviewed journal published by Mary Ann Liebert, Inc.

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Margaret Naeser, PhD, LAc, VA Boston Healthcare System, Boston University School of Medicine, and colleagues from Massachusetts General Hospital, and Harvard-MIT Division of Health Sciences and Technology, in Boston, and MedX Health Inc. (Mississauga, ON, Canada), report on the use of transcranial LED-based light therapy to treat two patients with longstanding traumatic brain injury (TBI). Each patient applied LEDs nightly and demonstrated substantial improvement in cognitive function, including improved memory, inhibition, and ability to sustain attention and focus. One patient was able to discontinue medical disability and return to full-time work. These cognitive gains decreased if the patients stopped treatment for a few weeks and returned when treatment was restarted. Both patients are continuing LED treatments in the home. The findings are presented in "Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumatic Brain Injury: Two Case Reports."

Low-level light therapy using lasers or externally placed LEDs to deliver red and near-infrared (NIR) light energy has been shown in cell-based studies to improve cellular metabolism and to produce beneficial physiological effects. In acute stroke in humans, for example, transcranial NIR light therapy applied less than 24 hours post-stroke was associated with improved outcomes.

"The results of this study will provide a basis for future therapeutic use of phototherapy to improve recovery after injury and facilitate management of other CNS disorders. The development of novel therapies to restore function after neurologic injury, stroke, or disease is an increasingly important goal in medical research as a result of an increase in non-fatal traumatic wounds and the increasing prevalence of dementias and other degenerative disorders in our aging population," says Raymond J. Lanzafame, MD, MBA, Editor-in-Chief of the Journal.

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Device measures brain temperature non-invasively: Monitoring could be critical in life-saving cooling therapy

ScienceDaily (May 3, 2011) — Doctors have long sought a way to directly measure the brain's temperature without inserting a probe through the skull. Now researchers have developed a way to get the brain's precise temperature with a device the diameter of a poker-chip that rests on a patient's head, according to findings presented May 1 at the annual meeting of the Pediatric Academic Societies in Denver.

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"This is the first time that anyone has presented data on the brain temperature of a human obtained non-invasively," said principal researcher Dr, Thomas Bass, a neonatologist at Children's Hospital of The King's Daughters in Norfolk, Va., and a professor of pediatrics at the hospital's academic partner, Eastern Virginia Medical School.

The research also suggests that an injured brain can be significantly warmer than the body, a finding critical to cooling therapies that reduce brain damage in everyone from elderly heart attack victims to hypoxic newborns.

"Knowing the actual brain temperature may allow us to improve outcomes by keeping the brain at an optimum temperature," said Dr. Bass.

With the help of a $750,000 National Institutes of Health grant, a research team led by Dr. Bass adapted an instrument that calculates temperatures by detecting microwave emissions produced by all human tissue.

Those microwaves pass unimpeded through the skull, like light passing through a sheet of glass. As tissue temperatures increase, the emissions grow more intense. Engineers calibrated the device to measure the temperature of brain tissue 1.5 centimeters beneath the skull.

In the trial whose results were presented, the device was placed on the heads of infants undergoing cooling therapy at CHKD. The device's brain temperature readings were correlated with rectal and esophageal temperatures. The difference in temperature between the brain and the body recorded by other means was as high as 5.4% Fahrenheit.

"That's difference is larger than we expected," Dr. Bass said.

Dr. Bass, who pioneered research on cooling therapy for hypoxic newborns, and set about this research because he believed the therapy could be improved if doctors knew precise temperature of the damaged organ, the brain.

Hypoxic brain damage in infants occurs most often in full-term births when the child suffers oxygen loss either immediately before or during delivery. Because of a quirk in the brain, a child can be revived but brain cells continue to die over several days, resulting in brain damage or death. Doctors could do little to stop this progression; parents often watched helplessly as their sons and daughters literally died before their eyes.

Based on the observation that children rescued from freezing ponds after extended periods of time suffered little or no brain damage, cooling therapy involves chilling an infant's body to 92 degrees for 72 hours after brain injury.

A clinical trial on the therapy showed that cooling the child stops or reduces the progression of brain cell death, drastically reducing brain damage and death. The results were so positive that the therapy is now standard in advanced neonatal intensive-care units worldwide.

Cooling therapy is now used with other patients as well, including heart attack victims whose brains have suffered oxygen deprivation.

Because cooling therapy's success relies on the temperature of the brain, precise readings of the brain's temperature is likely to improve a therapy that's already proven remarkably effective.

Children's Hospital of The King's Daughters is the only freestanding pediatric hospital in Virginia.

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