Red tide algae provides hope for stroke victims

by Daniel Bowden
Wednesday, November 28, 2012

Staff photo by Joshua Curry 

Professor Dan Bayden’s natural product studies at the University of North Carolina Wilmington Center for Marine Science shows promise in stroke recovery treatment.

In a study conducted in collaboration with Creighton University and Scripps Institute, brevetoxin-2, a naturally occurring compound cultured at the University of North Carolina Wilmington’s Center for Marine Science, has shown promise in aiding the rehabilitation of victims of traumatic brain injuries such as stroke.

In the study, which was conducted by Dr. Thomas Murray of Creighton University, brevetoxin-2 was applied to cultured (laboratory grown) mouse cells in very small doses. The result was stimulation of nerve cell growth and an increase in plasticity for existing nerve cells. Plasticity — the ability of nerve cells to adapt to events — is what allows the brain to “rewire” itself after a stroke or other traumatic events. The brain can’t revive dead nerve cells, but it can find ways to work around them.

“This has been decades in the making,” said Dr. Dan Baden, director of the Center for Marine Science at UNCW and co-author of the study. “We’ve made over 20 derivatives of this material over the last two decades.”

While the actual experiments involving cultured mouse cells are conducted at Creighton University, the brevetoxin-2 is cultured at UNCW. In culturing the brevetoxin-2, researchers at UNCW are able to manipulate the compound, and modulate the toxicity of molecules Murray uses in his studies. 

“Every few years he asks us to tweak the material and send it back,” Baden said. “It’s collaboration at its finest.”

Brevetoxin-2 is derived from the organism Karenia brevis, a marine algae that causes the red tide off the coast of Florida. Toxic even in small doses, exposure to this algae in its natural settings has been known to cause a variety of respiratory problems in humans, and kill dogs that have eaten contaminated shellfish.

Baden said that in relation to brevetoxin-2’s medical use, its high toxicity is a good thing.

“That just means that the therapeutic index is very small,” Baden said. “You need less of it to achieve the desired effect.”

The desired effect is neuron stimulation. Brevetoxin-2 has been shown to depolarize sodium channels in nerve cells, which causes the channels to open and neurons to fire. This stimulates the synthesis of synapses and the development of filapodial tissue, both of which are essential for cell communication. 

“Any material that causes a sodium channel to open and a neuron to fire is going to result in nerve conduction, which results in nerve growth,” Baden said.

Baden compared sodium channels to doors. Just like a door, sodium channels open and close, but they require energy. These doors act like they have a spring holding them shut. When brevetoxin-2 is applied, the door is pushed open and the neuron begins to fire through the entrance. If the door opening is too narrow, nothing escapes. If the door opening is too wide, the neuron fires too much. By carefully regulating the amount of brevetoxin-2 applied, the door can be opened in a predictable manner, and the neuron can fire at a pace conducive to nerve cell growth and plasticity.

“Brevetoxin causes the door to open and acts as a doorstop to stop it from closing,” Baden said. “Different derivatives control how long the door stays open and how inhibited it is from closing. We modulate how fast sodium channel doors open and close.”

In addition to brevetoxin-2, Karenia brevis is being used to derive two other compounds of interest for researchers: -brevinal and brevisin. Brevinal is currently being used to develop drugs for cystic fibrosis treatment, and brevisin is being looked at as a drug carrier. In order for a drug to deliver its effect, it has to cross membranes into a cell. Brain cells have a special protective barrier called the blood-brain barrier, and both brevetoxin and brevesin pass the blood-brain barrier very easily.

“We’re taking toxic things and turning them into therapeutic things,” Baden said.

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