Researchers will examine in a rat model of stroke whether adult stem cells may repair leaky blood-brain barrier

Tampa, FL (Aug. 11, 2011) – University of South Florida Department of Neurosurgery and Brain Repair faculty members have received a $2.6 million grant from the National Institutes of Health to investigate whether cells derived from human bone marrow may improve post-stroke therapy by repairing the blood-brain barrier.  This barrier prevents harmful substances in circulating blood from entering the brain while allowing passage of needed substances.

Current treatment for ischemic stroke is limited to one FDA-approved drug, the serine protease tissue-type plasminogen activator (tPA), which must be administered within three hours  following a stroke to be effective, according to the researchers.

“Although there are almost 800,000 stroke cases yearly in the United States, less than 3 percent of patients benefit from tPA treatment,” said Dr. Svitlana Garbuzova-Davis, one of the grant’s principal investigators and an assistant professor in the USF Department of Neurosurgery and Brain Repair. “New drugs are desperately needed, because of tPA’s narrow three-hour therapeutic window and its detrimental side effects that can exacerbate stroke injury and counteract the benefits provided by reperfusion of the occluded artery.”

Dr. Svitlana Garbuzova-Davis

According to Dr. Garbuzova-Davis, any treatment aimed at repairing stroke deficits should consider the pivotal role of blood-brain barrier repair to maintain central nervous system stability and enhance neuronal regeneration.

“Permanent blood-brain barrier damage can lead to harmful serum protein leakage into ischemic brain tissue and may result in severe brain swelling in the hours and days following a stroke,” she said. “This damage could negatively influence central nervous system regenerative processes after stroke.”

Using rat model of stroke, the researchers will investigate how blood-brain barrier repair might mitigate  functional recovery in the stroke animals, and determine if blood-brain barrier reconstitution can lead to positive therapeutic outcomes. Their research is aimed at discovering a potential mechanism underlying the repair promoted by stem cell transplantation.

“We believe that a regenerative mechanism involving the repair of the damaged blood-brain barrier by endothelial progenitor cells derived from bone marrow is critical to the successful outcome of cell therapy in stroke,” Dr. Garbuzova-Davis said. “While other cell-based technologies are largely designed to circumvent the blood-brain barrier for delivery of cells or drugs from the periphery into the brain, we are taking a novel approach of repairing the barrier damage to lead to a therapeutic outcome for stroke victims.”

Site-specific  recruitment of  endothelial progenitor cells (EPC), followed by blood vessel repair processes, is important to exploiting blood-brain barrier repair, a neglected therapeutic approach in stroke therapy, according to the investigators.  The USF studies are designed to examine whether EPC transplantation extends the therapeutic window of tPA for stroke, building on the the researchers’ long-standing goal of translating cell therapy from the laboratory to the clinic.

“If blood-brain barrier restoration through EPC transplantation alone or in combination with tPA proves effective, direct clinical application of this cell therapy could help a large population of ischemic stroke patients who may have missed the limited three-hour tPA window,” said Dr. Paul R. Sanberg, director of USF’s Center of Excellence for Aging and Brain Repair.

-USF Health-

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