The new study shows GCSF impacts both bone marrow and brain to improve cognition

Tampa, FL (July 1, 2009) -- A human growth factor that stimulates blood stem cells to proliferate in the bone marrow reverses memory impairment in mice genetically altered to develop Alzheimer’s disease, researchers at the University of South Florida and James A. Haley Hospital found. The granulocyte-colony stimulating factor (GCSF) significantly reduced levels of the brain-clogging protein beta amyloid deposited in excess in the brains of the Alzheimer’s mice, increased the production of new neurons and promoted nerve cell connections.

The findings were reported online in Neuroscience earlier this month and will appear in the journal’s print edition in August.

GCSF is a blood stem cell growth factor or hormone routinely administered to cancer patients whose blood stem cells and white blood cells have been depleted following chemotherapy or radiation. GCSF stimulates the bone marrow to produce more white blood cells needed to fight infection. It is also used to boost the numbers of stem cells circulating in the blood of donors before the cells are harvested for bone marrow transplants. Advanced clinical trials are now investigating the effectiveness of GCSF to treat stroke, and the compound was safe and well tolerated in early clinical studies of ischemic stroke patients.

“GCSF has been used and studied clinically for a long time, but we’re the first group to apply it to Alzheimer’s disease,” said USF neuroscientist Juan Sanchez-Ramos, MD, PhD, the study’s lead author. “This growth factor could potentially provide a powerful new therapy for Alzheimer’s disease – one that may actually reverse disease, not just alleviate symptoms like currently available drugs.”

Microglia (in green) attack the beta amyloid deposits (red) in GCSF-treated Alzheimer's mice.

The researchers showed that injections under the skin of filgrastim (Neupogen®) -- one of three commercially available GCSF compounds -- mobilized blood stem cells in the bone marrow and neural stem cells within the brain and both of these actions led to improved memory and learning behavior in the Alzheimer’s mice. “The beauty in this less invasive approach is that it obviates the need for neurosurgery to transplant stem cells into the brain,” Dr. Sanchez-Ramos said.

Based on the promising findings in mice, the Alzheimer’s Drug Discovery Foundation is funding a pilot clinical trial at USF’s Byrd Alzheimer’s Center. The randomized, controlled trial, led by Dr. Sanchez-Ramos and Dr. Ashok Raj, will test the safety and effectiveness of filgrastim in 12 patients with mild to moderate Alzheimer’s disease

The researchers worked with 52 elderly mice, equivalent to the human ages of 60 to 80 years. About half (24) were mice genetically altered to develop symptoms mimicking Alzheimer’s disease by the time they reach 5-months old. The others (28 normal, or non-Alzheimer’s, mice) were not. The researchers confirmed through a series of tests that the Alzheimer’s mice were memory impaired before beginning the experiments.

Some mice were treated for three weeks with injections of the GCSF compound filgrastim. At the end of study, the Alzheimer’s mice treated with GCSF demonstrated clearly improved memory, performing as well on behavioral tests as their non-Alzheimer’s counterparts. The Alzheimer’s mice administered saline injections instead of GCSF continued to perform poorly. GCSF treatment did not boost the already excellent memory performance demonstrated by the non-Alzheimer’s mice tested before the study began.

Based on the promising findings in mice, Dr. Juan Sanchez-Ramos and Dr. Ashok Raj will lead a pilot clinical trial at the USF Byrd Center testing GCSF (filgrastim) in patients with mild to moderate Alzheimer's disease.

Further experiments showed that the size and extent of beta amyloid deposited in the brains of the Alzheimer’s mice was significantly less in those treated with GCSF. Depending on their ages, mice treated with GCSF had a 36 to 42-percent reduction in beta amyloid, the protein considered a major culprit in the development of Alzheimer’s disease.

GCSF reduced the burden of beta amyloid deposited in the brains of the Alzheimer’s mice by several means, the researchers found. One was by recruiting reinforcements to clear beta amyloid accumulating abnormally in the brain. The growth factor prodded bone-marrow derived microglia outside the brain to join forces with the brain’s already-activated microglia in eliminating the Alzheimer’s protein from the brain. Microglia are brain cells that act as the central nervous system’s main form of immune defense. Like molecular “Pac-men,” they rush to the defense of damaged or inflamed areas to gobble up toxic substances.

The growth factor also appeared to increase the production of new neurons in the area of the brain (hippocampus) associated with memory decline in Alzheimer’s disease and to form new neural connections.

“The concept of using GCSF to harness bone marrow-derived cells for Alzheimer’s therapy is exciting and the findings in mice are promising, but we still need to prove that this works in humans” said Dr. Raj, a physician researcher at the Byrd Alzheimer’s Center at USF Health.

In addition to Dr. Sanchez-Ramos, other authors of the Neuroscience paper were Shijie Song, PhD; Vasyl Sava, PhD; Briony Catlow, PhD; Xiaoyang Lin; Takashi Mori, PhD; Chuanhai Cao, PhD; and Gary Arendash, PhD. The study was funded by grants from the Alzehimer's Drug Discovery Foundation, Helen Ellis Foundation, Florida Alzheimer's Disease Research Center, and the Byrd Alzheimer's Center at USF.

- USF Health -

USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $360 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching.

- Photo by Eric Younghans, USF Health Communications

USF Health Department of Neurosurgery and Brain Repair

USF Health’s Department of Neurological Surgery and Rehabilitation has been one of the top 10 departments in the nation in attracting research funding, and is now changing its name to reflect its dedication to developing new therapies for patients. The new name, USF Department of Neurosurgery and Brain Repair, reflects USF Health's commitment to high-impact science as the underpinning of health care.

Below is a departmental letter explaining the name change. This department works closely with other clinical departments focused on the brain, including the Department of Neurology, and the Department of Psychiatry and Behavioral Medicine.

USF Department of Neurosurgery and Brain Repair

Why the name change? The name change from the Department of Neurological Surgery and Rehabilitation to Department of Neurosurgery and Brain Repair represents the true strength of the department, which is harnessing a balanced approach between its clinical mission and its research expertise in clinical, translational, and basic research and education.

With 12 full-time neurosurgeons based at USF-Tampa General Hospital (TGH) and 12 full-time research faculty members housed in the Center of Excellence for Aging and Brain Repair (CABR), the blended departmental name of these two collaborative entities demonstrates to the College and University the unity of the CABR with USF Neurosurgery. This name change fits the description of our department as one of the most distinct clinical and basic science neurosurgical departments in the nation. It highlights the department’s core interest in treating brain disorders, capturing the current worldwide theme of translational research, especially focused on the field of regenerative medicine emphasizing the use of neurosurgical tools for brain repair.

Indeed, the theme of neurosurgery and brain repair epitomizes the roadmap of hot topic research areas solicited by NIH, VA, DOD and other federal agencies and private foundations. Our goal is to attract and train prospective medical students, residents, fellows and faculty members who have interest in developing their career in a department with a solid clinical faculty and a strong research arm. Equally important, drawing from our milestone achievements in lab-to-clinic cell-based neurosurgical therapies for Parkinson’s disease and stroke, we envision continuing our leading role in introducing safe and effiective treatments for brain disorders, thereby saving lives and improving the quality of daily living for patients who otherwise face a fatal or morbid prognosis.

In summary, the Department of Neurosurgery and Brain Repair appeals to academia, as well as the public and media, to recognize our department as a unique nurturing environment for physicians and scientists in advancing evidence-based applications of cutting-edge laboratory discoveries to the clinic.

Harry van Loveren, MD
Chair, Department of Neurosurgery and Brain Repair

Paul R. Sanberg, PhD, DSc
Director, Center of Excellence for Aging and Brain Repair

- Photo by Matthews Photography, Inc.

L to R: Dr. Jorge Marcet, director of the Division of Colorectal Surgery, with general surgery residents Dr. Beth Krieger (1st place research award) and Abhishek Mathur (3rd place) at the American College of Surgeons Florida Chapter annual scientific meeting.

Two USF surgery residents were among the three winners of a high-profile research presentation last month at the Florida Chapter of the American College of Surgeons 2009 Scientific Annual Meeting in Palm Coast, FL.

Beth Krieger, MD, who is completing a one-year research fellowship in the Division of Colorectal Surgery, won first place in the Florida ACS “Edward M. Copeland Annual Paper Competition” for her research paper titled “Long-term Results of Transanal Excision for Locally Advanced Rectal Cancer Following Neoadjuvant Therapy.” The retrospective study found that transanal excision is an effective alternative to radical surgery for select patients with advanced lower rectal cancer who have complete disappearance of their cancer following preoperative chemotherapy and radiation. Krieger, who will be a fourth-year general surgery resident in July, received a $1,000 award.

Abhishek Mathur, MD, a first-year general surgery resident, won third place for his paper titled “Site of Recurrence after Pancreatectomy for Pancreatic Adenocarcinoma Is Not Influenced by Margin Status or Adjuvant Chemoradiotherapy, But Can Impact Survival.” He received a $250 award.

Dr. Krieger and Dr. Mathur were among 10 residents from medical schools across Florida invited to present the findings of their research papers at the chapter’s annual scientific meeting. The winning papers were selected from among more than 60 submitted by residents in surgical specialties.

The annual Edward Copeland competition focuses on resident research related to clinical surgery outcomes. Originality and applicability of research to practice are among the criteria for the award.

- Newsbrief by Anne DeLotto Baier, USF Health Communications

Linda Nelson, ARNP, MSN (left), nurse manager for clinical operations at the South Tampa Center for Advanced Healthcare, and Valerie Williams, BSN, MBA, assistant director of nursing/clinical systems, greet visitors at the Neighborhood Care Center reception.

TAMPA, Fla. (June 22, 2009) – Tampa-based Sweetbay Supermarket continues to strengthen its home-grown roots by deepening its partnership with USF and collaborating on the Florida-based chain’s first in-store wellness clinic. USF Health Neighborhood Care Center, scheduled to open July 16 with two ARNPs, will be featured inside the store at its newest location in New Tampa.

“We are proud to offer the New Tampa community an in-store neighborhood care center where they can have convenient access to high-quality medical services that fit their needs,” notes Mike Vail, president and COO of Sweetbay Supermarket. “This service helps make our shoppers’ lives more convenient and the comprehensive quality of care that USF Health provides is exactly what we want to offer the New Tampa community.”

The USF Health Neighborhood Care Center will offer a variety of services through an advanced registered nurse practicioner. From common illnesses to camp physicals and vaccines, patients can visit the Neighborhood Care Center, and then be referred into the network of more than 350 doctors in the USF Physicians Group for further treatment if needed.

Dr. Stephen Klasko, far right, announces the opening of the USF Health Neighborhood Care Center inside the new Sweetbay Supermarket in New Tampa.

“This effort continues our exciting partnership with Sweetbay Supermaket, allowing USF Health to directly impact the health of residents in New Tampa and Wesley Chapel,” said Stephen K. Klasko, CEO of USF Health and Dean of the College of Medicine. “We are excited to bring our commitment to advanced, high-quality healthcare to this growing area in our community.”

Sweetbay’s new store location is 6425 County Line Road, Tampa FL 33647. Store hours are 7 am to 11 pm. Sweetbay operates pharmacies at USF Health's Morsani Center for Advanced Healthcare and the South Tampa Center for Advanced Healthcare.

About Sweetbay Supermarket
Sweetbay Supermarket provides a one-of-a-kind shopping experience, built from the ground up and developed from research in core markets to express the vibrant, exciting and diverse tastes, colors and aromas of food important to Floridians. Sweetbay offers outstanding value, quality and variety, routinely partnering with Florida growers, to bring shoppers the freshest food available in the state. Sweetbay Supermarket was launched in November 2004 in Largo and is headquartered in Tampa. Sweetbay has 103 stores in Florida.

About USF Health
USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $360 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching.

- Photos by Susanna Martinez Tarokh, USF Health Communications

Time to squelch that cigarette.

The entire campus of USF Health is going smoke-free, starting Nov. 19, the same day as the annual Great American Smoke-Out.

But the signs announcing the pending ban went up last week, making the end all but official.

Sign installer Bill Gaw posts the news.

"We're doing this because we are a health institution, and promoting a smoke-free environment at USF Health is perceived to be one more instance of USF Health promoting good health habits," said Steven Specter, PhD, associate dean for student affairs and leader of a task force to implement the ban.

The task force also is publicizing programs to help smokers kick the habit, said Leila Martini, assistant director of tobacco prevention and cessation for USF's Area Health Education Center Program.

"It's hard to quit, so we're trying to help them," she said. "We're trying to make it as easy as possible."

The push to move smoking off campus started with medical students who were disturbed by the contradiction of a school promoting health yet allowing unhealthy behavior, Dr. Specter said. Around the same time, AHEC received funds to put together a smoking cessation program.

The students also are working on a plan to lobby legislators for outdoor smoking to be banned on medical school campuses, Dr. Specter said.

State law already bars smoking indoors in most public places.

The ban will extend around the entire USF Health campus. That means the Colleges of Nursing, Medicine and Public Health, but also patient care spaces, such as the Morsani Center, the Children's Medical Services building, and the medical clinic; and outlying buildings, such as the Byrd Alzheimer's Institute.

The ban will extend the smoke-free area on the USF campus. Last year, H. Lee Moffitt Cancer Center & Research Institute enacted a smoking ban on its campus.

However, the ban will be enforced gently. There will be no smoking police. Instead, if people are seen smoking on campus, they will be given a business-size card explaining the ban and listing phone numbers for smoking cessation programs.

So far, Dr. Specter hasn't heard directly from anyone opposed to the ban. He approached one of his employees, a smoker, and asked him about it.

"His response was, ‘I'll just have to not smoke here,' " Dr. Specter said. "I'm sure there are some smokers who are unhappy, but nobody's come forward."

Task force member Gary Stein, MPH, tobacco programs coordinator for the Hillsborough County Health Department, praised USF Health for enacting the ban.

"Tobacco is the only thing sold in the U.S. that, when used as directed, kills its user," he said. "USF Health, by its name and its nature, is the harbinger of health. It doesn't make sense for USF Health to facilitate the use of tobacco."

Other members of the task force are: Dr. Mathis Becker; Dr. Dennis Penzell; Danielle Schutz; Dr. Lonna Gordon, a 2009 graduate of the College of Medicine; Dr. Daniel Mauriello, a 2008 graduate; and medical student Byron Moran.

******
Need help quitting?

The task force is referring smokers to these programs:

Florida Quit Line 1-877-U-CAN-NOW
USF Employee Assistance Center 974-5469
USF Counseling Center 974-2831
USF Student Health Services 974-2331
Florida Area Health Education Center (AHEC) Network 1-87-QUIT-NOW-6 (1-877-848-6696)

- Story by Lisa Greene, USF Health Communications
- Photos by Eric Younghans, USF Health Communications

USF Health urogynecologist Lennox Hoyte, MD, will be featured as the guest medical expert 1 to 2 p.m., this Sunday, June 28, on the Focus on Females Radio Healthcare Clinic aired on Talk Radio 860 AM. Dr. Hoyte, director of the Division of Female Pelvic Medicine and Reconstructive Surgery at USF, will discuss “Pelvic Pain” with the show’s host Dr. Steven Maskin and listeners who call in.

Dennis Ledford, MD, a professor of medicine and pediatrics in the Division of Allergy and Clinical Immunology at USF Health and the James A. Haley VA Medical Center, is scheduled to speak about “Asthma In and Out of Pregnancy” on the July 12 Focus on Females show.

In addition to Dr. Hoyte and Dr. Ledford, dermatologist Mary Lien, MD, and gastroenterologist H. Juergen Nord, MD, have represented USF Health on past shows.

The radio healthcare program is intended to help consumers become informed about their individual medical problems, through dynamic and interactive educational programs. Physician guests answer real questions and provide practical, ready-to-use information on a wide variety of topics, the program’s website says. “Participation empowers families to better partner with their doctors.”

If you’d like to have your case discussed, call the show between 12:30 and 1 p.m, or call in during the show to ask a question or comment. In Hillsborough, call 813-289-1860, and anywhere else toll free, 877-969-8600. Podcasts of past shows are available at www.focusonfemales.com/radio.php, and shows are also streamed live from that site.

MRSA infections that are transmitted from dogs and cats to their human handlers, and vice-versa, are increasing—with infections of the skin, soft-tissue, and surgical infections the most common.

MRSA, or methicillin-resistant Staphylococcus aureus, is a term often used to describe staph infections that are resistant to antibiotics. This and other bite-related and septic syndromes caused by cats and dogs are discussed in a Review in the July 2009 edition of The Lancet Infectious Diseases, written by Dr. Richard Oehler and colleagues at the USF College of Medicine and James A. Haley Veterans' Hospital.

In the United States, dog and cat bites make up roughly 1 percent of emergency room visits yearly, with similar numbers reported in Europe. Women and the elderly are most at risk of being bitten by a cat. Men in general and those younger than 20 of both sexes are most likely to be injured. Most bite exposures occur in young children, involve unrestrained dogs on the owner’s property, and about 20 percent involve a non-neutered dog.

Risk is highest in young boys ages 5 to 9, because of their small size and lack of understanding of provocative behaviour, the authors write. Children, due to their small height, often receive bites to the face, neck, or head. Adults are most frequently bitten on the hand, followed by face, scalp, neck, thigh or leg.

Proper treatment of dog and cat bites should involve treatment of the immediate injury (whether superficial or deep) and then management of the risk of acute infection, including washing with high pressure saline if possible, and antibiotics in selected cases.

Severe infections can develop in about 20 percent of all cases, and are caused by Pasteurella, Streptococcus, Fusobacterium, and Capnocytophaga bacteria from the animal’s mouth, plus possibly other pathogens from the human’s skin. In countries with endemic rabies, rabies prophylaxis should be considered.

Sepsis can be a severe complication of bite wounds, particularly those infected with C canimorsus, P multocida, Staphylococcus spp (including MRSA), and Streptococcus spp. Meningitis, endocarditis, and peritonitis can also complicate bite-wound infections. Several other species, including Bacteroides, Fusobacterium, Neisseria, and Prevotella, might also produce bite-wound sepsis in individuals with leukaemia and lupus, and in those receiving chronic steroids.

As community-acquired strains of MRSA increase in prevalence, a growing body of clinical evidence has documented MRSA colonization in domestic animals, often implying direct acquisition of S aureus infection from their human owners. MRSA colonization has been documented in companion animals such as horses, dogs, and cats, and these animals have been viewed as potential reservoirs of infection.

MRSA-related skin infections of pets seem to occur in several manifestations, including simple dermatitis, and even perineal cellulitis, and can be easily spread to owners. Some people carry MRSA germs in their noses or on their skin without realizing it, but the bacteria do not cause infection unless they enter the body -- through a bite or open wound, for instance.

Specific therapy for pet-associated MRSA infections is similar to regimens used in most community-acquired MRSA syndromes. “Much more remains to be learned about MRSA and pet-associated human infections," the authors write.

“Pet owners are often unaware of the potential for transmission of life-threatening pathogens from their canine and feline companions. Bite injuries are a major cause of injury in the USA and Europe each year, particularly in children. Bites to the hands, forearms, neck, and head have the potential for the highest morbidity," they conclude.

"Health-care providers are at the forefront of protecting the vital relationships between people and their pets. Clinicians must continue to promote loving pet ownership, take an adequate pet history, and be aware that associated diseases are preventable via recognition, education, and simple precautions.”

Other USF/VA authors of the The Lancet Infectious Diseases review were Dr. Sandra Gompf, Dr. Ana Velez, and Dr. Jorge Lamarche.

- Source: Press Release from The Lance Infectious Diseases

CLEARWATER, Fla. (June 22, 2009) -- The new USF-Morton Plant Mease Primary Care Sports Medicine Fellowship will start its first fellow next month after recently receiving full accreditation from the Accreditation Council for Graduate Medical Education.

Fellows are doctors who are receiving specialized graduate medical education in a subspecialty. They already have completed medical school and graduate training, or residency, in a primary specialty.

“We’re delighted to be able to train more doctors for careers in sports medicine,” said Dr. Eric Coris, director of the University of South Florida’s Sports Medicine Division, co-director of the fellowship, and associate professor of family medicine. “With a population that is aging but also more active, there’s an incredible need for more physicians who can care for people with athletic injuries and help them stay healthy and active.”

The fellowship program will be based at the Turley Family Health Center in Clearwater. The health center, operated by Morton Plant Mease, provides comprehensive health care services to a diverse group of patients without regard to a patient’s ability to pay.

“The program will offer the fellows the opportunity to learn in various training environments,” said Dr. Sean Bryan, co-director of the fellowship and a USF affiliate associate professor of family medicine.

“This is a best of both worlds situation,” Dr. Bryan said. “Imagine having the resources of a strong community health system and a major academic health center at your disposal.”
Fellows will receive training from USF primary care sports medicine faculty as well as from USF and community orthopedic surgeons, cardiologists, other specialists and allied health professionals, Dr. Bryan said.

“We understand that to provide the best care for athletes, you need a multi-disciplinary team approach,” he said.

As part of their training, the fellows will help support community sports events and activities, including the St. Anthony’s Triathlon and the Morton Plant Mease Triathlon. They’ll also help care for students in USF Athletics, under the supervision of USF faculty members.

“We’re fortunate to have access to a wide range of athletes in high school, Division I college, professional baseball, football and multiple triathlons. This will provide significant depth to our training,” Dr. Bryan said.

Core faculty members for the fellowship will include: Dr. Bryan; Dr. Coris; Dr. Ted Farrar, associate director of the fellowship; and Dr. Michelle Pescasio, assistant director of the fellowship.

The USF College of Medicine created the USF Sports Medicine Institute, which is dedicated to caring for athletes of all ages and skill levels, as well as people who are physically active at home and at work. The institute’s providers offer diagnosis and treatment of all athletic injuries, as well as expert pre-sports participation exams.

Nationally recognized for health care excellence, Morton Plant Mease Health Care is dedicated to providing community owned health care services that set the standard for high-quality, compassionate care. Morton Plant Mease Health Care is comprised of the following hospitals – Morton Plant, Clearwater; Mease Dunedin, Dunedin; Mease Countryside, Safety Harbor and Morton Plant North Bay, New Port Richey.

About USF Health
USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $360 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching.

About Morton Plant Mease
Nationally recognized for health care excellence, Morton Plant Mease Health Care is dedicated to providing community owned health care services that set the standard for high-quality, compassionate care. Morton Plant Mease Health Care is comprised of the following hospitals – Morton Plant, Clearwater; Mease Dunedin, Dunedin; Mease Countryside, Safety Harbor and Morton Plant North Bay, New Port Richey.

- USF Health neuroscientist led the rat-model study -

Tampa, FL (June 17, 2009) -- Using an opioid drug to induce hibernation in rats reduces the damage caused by an artificial stroke, reports a study published today in the open access journal BMC Biology. Researchers found that those animals put into a chemical slumber -- a hibernation-like state that cooled their brains -- suffered less behavioral impairment after a period of cerebral artery blockage than control rats.

Cesar Borlongan, PhD, a neuroscientist at the University of South Florida Center for Aging and Brain Repair in Tampa, FL, worked with a team of researchers from the National Institutes of Health, to investigate the role of the opioid system in brain injury and protection.

“Studies in hibernating and active squirrels have shown that ‘natural hibernation’ has anti-ischemic effects – protecting against the formation of blood clots. We’ve shown that a drug that induces hibernation can achieve similar results in the brain,” Borlongan said. “Even a small decrease in the brain’s temperature appears to be neuroprotective.”

Borlongan and his colleagues dosed the rats intravenously with [D-ala2,D-leU5]enkephalin (DADLE), a drug from the same pharmaceutical family as morphine and heroin. DADLE is used to cryogenically preserve donated organs to keep them viable for transplantation. The researchers found that, after an experimental stroke, the pre-treated animals performed better than control rats in a series of behavioral tests. DADLE significantly reduced the size of the stroke, and prevented cell death processes and behavioral abnormalities.

“The observation that this substance, previously shown to induce hibernation, improves recovery from cerebral ischemia means it could provide a new pharmacological treatment for stroke,” Borlongan said.

During ischemic stroke, diminished blood flow and oxygen trigger a cascade of events that may cause additional, delayed damage to brain cells. DADLE helped the stroke-damaged area of the brain survive this assault, Borlongan said. More studies, including injection of the drug following a stroke, are needed to determine exactly how the drug works. But Borlongan suggests that it may promote proliferation of the body’s own natural stem cells, which then migrate from bloodstream to the brain to control and repair damage.

- USF Health -

USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $360 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.health.usf.edu

- BMC Biology -

BMC Biology - the flagship biology journal of the BMC series - publishes research and methodology articles of special importance and broad interest in any area of biology and biomedical sciences. BMC Biology (ISSN 1741-7007) is covered by PubMed, MEDLINE, BIOSIS, CAS, Scopus, EMBASE, Zoological Record, Thomson Reuters (ISI) and Google Scholar.

RELATED STORY:
USF neuroscientist advances stem cell therapy for stroke

Dr. Borlongan explores body’s own bone marrow-derived cells as source of repair

- The Lancet Lifeline Interview with Dr. Borlongan

Neuroscientist Cesar Borlongan, PhD, a leading stem cell researcher, has returned to USF where his career began.

Cesar Borlongan has come full circle – back to the University of South Florida College of Medicine, where he began his neurosciences career as a postdoctoral fellow and aspiring stem cell researcher 16 years ago. This fall he joined the USF Center of Excellence for Aging and Brain Repair, where he is a professor and vice chair of research for the Department of Neurosurgery and Brain Repair.

In the interim, Dr. Borlongan was a senior staff fellow at the National Institute of Health’s National Institute on Drug Abuse, where he earned awards for outstanding scientific achievement and research excellence. The distinguished NIH tenure was followed by six years at Medical College of Georgia, where he directed the Institute of Molecular Medicine and the Department of Neurology Cell Transplantation.

“We are fortunate that a neuroscientist of Dr. Borlongan’s caliber has returned to USF,” said Paul R. Sanberg, PhD, DSc, distinguished professor of neurosurgery and director of the Center for Aging and Brain Repair. “He is one of the pioneers in cell therapy research for stroke and has been instrumental in advocating the consistent, rigorous design of preclinical studies so that findings can be readily translated to stroke treatment.”

Throughout his career Dr. Borlongan has focused on advancing stem cell therapy for brain disorders, particularly adult stroke and neonatal stroke. At the Center for Aging and Brain Repair, he works alongside other leading neuroscientists exploring the potential of neural cells and alternatives to embryonic stem cells (including adult bone marrow cells and cord blood cells) as treatments for brain injury and neurological diseases like Parkinson’s, Huntington’s, Alzheimer’s, stroke and ALS.

Dr. Borlongan brought a team of four postdoctoral fellows and a faculty member as well as a five-year NIH grant totaling more than $3.5 million to USF from Medical College of Georgia. He is working with USF Health neurosurgeons and neurologists and researchers at the Byrd Alzheimer’s Center to develop innovative treatments for stroke using stem cells. In particular, he is exploring ways to harness stem cells produced by the body’s own bone marrow – known as endogenous stem cells -- to repair or prevent brain damage from stroke.

If even small numbers of these outlying stem cells in the bloodstream could be coaxed to proliferate with growth factors or drugs and honed to the stroke-damaged area of the brain, the potential benefits could be substantial, Dr. Borlongan said. Because the cells originate in the person being treated, they would be recognized as “self” by the body and not trigger a potentially dangerous immune response.

“One of the major obstacles to cell transplantation has been graft rejection. When you introduce stem cells from a donor to a transplant recipient, the graft can always be rejected as a foreign substance. The patient can suffer infection and other adverse side effects,” Dr. Borlongan said. “But these problems, including the need for powerful immunosuppressants following transplantation, could be circumvented by using stem cells that come from the patient.”

Dr. Borlongan (above) brought $3.5-million NIH grant and a team of researchers with him to the USF Center for Aging and Brain Repair, including postdoctoral fellow SeongJin You, PhD (below).

“We’ve learned a lot in the last decade,” said Dr. Borlongan said. “I’m more optimistic than ever that we’ve jumped through the scientific hurdles needed to demonstrate the safety and effectiveness of stem cell therapy in animal models. We know what works in mice – but now we have to apply it to humans!”

Dr. Sanberg and Dr. Borlongan at USF, working with colleagues at the University of Pennsylvania, laid the foundation for the world’s first experimental procedure to repair brain damage in stroke patients. In 1998, surgeons at the University of Pittsburgh implanted human neurons derived from a tumor and rendered benign (hNT-neurons) into the brain of a patient who suffered a stroke the year before. The clinical trial was built in part on USF research showing that the hNT-neurons restored the movement of rats subjected to experimental stroke.

Since then, only a few small clinical trials of cell therapy for stroke have been reported. While there have been no complications directly related to the stem or progenitor cells, evidence about the cells’ effectiveness in restoring function in patients is still lacking.

Many rodent studies have demonstrated that stem cell transplantation -- by surgery, direct injections to the brain and less invasive IV infusion, can improve stroke recovery. But, the underlying reasons for the success of these therapies remain largely unknown. The researchers use various strains of rodents and stroke models; they implant, infuse and inject different cell types; they put the cells in different target locations in the brain and employ different behavior tests to assess functional recovery. All these variables, without standardized treatment protocols and outcome measures, make it difficult to compare studies and determine the best conditions for cell therapy following a stroke, Dr. Borlongan said.

Dr. Borlongan is investigating how the body's own bone marrow-derived stem cells (glowing in center of screen) could be prodded to rescue stroke-damaged regions of the brain.

In an editorial published last year in the journal Regenerative Medicine, Dr. Borlongan called for academia, industry, the NIH and the FDA to adopt translational research guidelines that would promote more consistency in designing preclinical studies and help advance cell therapy for stroke from laboratory to clinic.

“It is imperative for clinical translation that these cells be tested in multiple models of focal stroke, in both genders and in multiple laboratories,” he wrote.

- Story by Anne DeLotto Baier, USF Health Communications
- Photos by Eric Younghans, USF Health Communications

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