Tissue involved in brain development may offer new approach to stroke treatment

May 06, 2004

The same tissue that helps a developing brain form its protective blood-brain barrier may protect the adult brain from the ravages of stroke, researchers say.

The choroid plexus has been relegated as a bystander in the adult brain, says Dr. Cesario V. Borlongan, neuroscientist at the Medical College of Georgia and first author on a study published in the May issue of NeuroReport.

But within the last five years, researchers across the world have been compiling evidence that in response to stroke as well as other brain injury or disease, the tissue may actually stimulate the production of stem cells that could help replace damaged neurons and neurotrophic factors that nourish brain cells, Dr. Borlongan says.

This latest study is the first to show the therapeutic potential of that natural response: when biocompatible microcapsules containing these choroid plexus cells were placed on top of the brains of animal models for stroke, stroke damage was significantly reduced.

"The transplanted choroid plexus may provide a potential new therapy to reduce and repair damage from stroke," Dr. Borlongan says. However, he noted that much work remains to explore the potential, including whether the findings in animal models hold true for humans and the best way to deliver that protection.

"We found that these animals that got transplanted choroid plexus had very small stroke areas," Dr. Borlongan says. "This is the first indication that choroid plexus is important tissue for the formation of new stem cells and/or secretion of trophic factors."

The findings also are being presented at the 11th annual meeting of the American Society for Neural Transplantation and Repair May 6-9 in Clearwater Beach, Fla.

For his studies, Dr. Borlongan used choroid plexus cells taken from a rat or pig and placed inside tiny capsules designed by LCTBioPharma, Inc., in Providence, R.I., a subsidiary of Living Cell Technologies based in New Zealand and Australia. The capsules are designed to allow molecules, such as the neurotrophic factors, to escape and keep out inflammatory factors that could trigger an immune response and rejection.

"The next step is to do the same thing in a nonhuman primate model," says Dr. Borlongan, who will continue to document exactly how the choroid plexus reduces stroke size and resulting neurological and motor function damage, at least in animals.

"We know it does something," he says, but he is still working to determine if that 'something' is producing neurotrophic factors and stem cells.

Other challenges between laboratory findings and an actual new therapy include the probability that the reparative benefits of choroid plexus tissue are needed immediately after a stroke to minimize brain damage. "At this time, the FDA generally won't allow invasive procedures immediately after a stroke unless they are in hemorrhagic stroke patients who need surgery to stop their bleeding. But invasive procedures can be used for chronic stroke, patients who are really sick, debilitated and not responding," Dr. Borlongan says. The only FDA- approved drug therapy to date in the hours immediately following a stroke resulting from occlusion of a blood vessel is intravenous infusion of the clot-dissolving drug TPA.

That means the first clinical trials of this new approach likely would be in chronic patients, who may also benefit. "We want to show first that it's safe and second that it's feasible, that when you transplant these cells into a patient, they won't be rejected and the patient won't show any detrimental side effects," Dr. Borlongan says, estimating that such studies are at least a year away.

Still, despite the challenges ahead, he is excited about a therapy that augments the apparently natural healing response of this tissue, which is located inside the ventricles of an adult brain.

"We are trying to supplement a natural process," Dr. Borlongan says, that may have potential for stroke, Huntington's chorea and other neurodegenerative diseases as well as traumatic brain injury. "Transplanting choroid plexus tissue may open a whole new understanding of how to treat central nervous system disorders," he says noting other options that need pursuing such as medicines that could stimulate the choroid plexus of a stroke patient.
-end-


Medical College of Georgia at Augusta University

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