Stroke is a leading cause of death that causes substantial damage to the brain. Chassagnon and colleagues show that a protein derived from spider venom can help protect the brain from damage during a stroke and ultimately provide a new stroke treatment.
A stroke occurs when blood flow to the brain is cut off. Most strokes occur due to a blood clot in the brain. Strokes are the second-leading cause of death in the world. Even when they aren’t deadly, strokes can result in temporary or permanent disability. This is a result of brain damage that occurs from inadequate blood supply.
During a stroke, oxygen levels fall in brain cells. This forces the brain to change the way it makes energy from an oxygen-dependent process to an oxygen-independent, or anaerobic, process. This anaerobic process results in increased acidity within the cell. Increased acidity then triggers the opening of a specific ion channel. Ion channels allow sodium into or out of a cell, a mechanism that cells use to create an electrical current and communicate with each other. Opening up an ion channel causes most of the damage during stroke. Many therapies seek to target this reaction to reduce long-term brain damage. PcTx1, derived from tarantula venom, is a strong inhibitor of the acid-sensing ion channels that open during stroke.
In the Proceedings of the National Academy of Sciences, Chassagnon and colleagues describe a new spider venom protein, Hi1a, which may protect brain cells by inhibiting the function of ion channels. They collected three Australian funnel-web spiders in the wild. After isolating the venom glands, they identified and copied the Hi1a protein. This protein was similar to PcTx1 and the researchers wanted to test its therapeutic effects.
First, Chassagnon and colleagues tested the effects of Hi1a on frog egg cells that they modified to have human ion channels. The researchers manipulated the acidity of these cells. Then, they measured the electrical current generated by these cells with and without Hi1a treatment. What the researchers found is that Hi1a slows ion channel activity five-fold, independent of the acidity of the cell. In addition, relative to PcTx1, Hi1a took twice as long to wear off. Overall, Hi1a was better at protecting cells from damage than PcTx1, with cell survival rates of 77% versus 68%.
Afterwards, Chassagnon and colleagues tested the effect of this protein on laboratory rats. They induced strokes in rats and treated them with either Hi1a or with saline at time points of two, four, or eight hours after the stroke. The researchers assessed the severity of the stroke after one and three days and compared the results to a pre-stroke baseline. Three days after the induced strokes, the rats’ brains were analyzed for damage. Hi1a protected the brain from general damage and specifically protected the regions of the brain that had been directly affected by the stroke. Rats who received Hi1a had less impairment after stroke than those given saline. Furthermore, the treatment showed no adverse side effects. Interestingly, Hi1a was effective even if administered eight hours after the stroke.
Many stroke patients do not receive treatment until two hours after their stroke begins. It is possible that Hi1a’s long-term action would serve as an effective medication to protect brain cells from damage. This would lessen the disability caused by stroke, improving recovery and quality of life for stroke patients. Future work needs to focus on turning Hi1a into a new stroke treatment, and testing its safety and effectiveness in humans.
Written By: C.I. Villamil