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Lithium may be helpful in stroke recovery
Element affects expression of protective proteins in nerve cells, blood vessels
Issue date: 11/20/08
In an article in the journal Stroke, a team of researchers from Hopkins, Harvard and the National Institute of Mental Health showed that lithium may be useful for patients who have suffered a stroke, which is a sudden disturbance in bloodflow to the brain.
The team sought to determine how lithium helped the brain recover from a stroke. They knew the pathways lithium targets in the body.
They found that lithium promotes the production of growth factors in the cells along the blood-brain barrier, which may explain how lithium repairs damaged blood vessels after a stroke.
Lithium has been used as a treatment for a number of mood disorders, most notably bipolar disorder. Only recently has lithium appeared to be useful for non-psychiatric central nervous system disorders, such as strokes and Lou Gehrig's disease (ALS).
However, the typical dose of lithium used for treatment is only slightly below the toxic dose, so there is a high risk of overdosing.
If the mechanism by which lithium acts to help treat strokes or ALS were known, then scientists could develop less-toxic medications designed to use the same mechanism as lithium to treat those conditions.
Previous studies had shown that two proteins, brain-derived neutrophin factor (BDNF) and vascular endothelial growth factor (VEGF), contribute to repairing the blood vessels leading to the brain that are damaged in a stroke. Lithium improved recovery times after strokes in rats.
The experiment involved developing cultures of rat brain cells, then adding lithium, and finally measuring the change in BDNF & VEGF levels over time. BDNF levels did not change; however, exposure to lithium caused VEGF levels to increase to as much as quadruple initial VEGF levels.
To determine which pathway lithium uses, synthetic inhibitors of the pathways lithium targets in the body were added to rat brain cells, and the results were compared to what was found when the cells were exposed to lithium.
One pathway, the inhibition of a protein called glycogen synthase kinase-3, has been previously shown to regulate VEGF levels. The team showed that lithium uses this pathway to increase VEGF levels, and thus, speed up repair of damaged tissue.
The effect of lithium on VEGF levels may explain the recent discovery that lithium may improve survival in patients suffering from ALS. VEGF has been proposed to help protect neurons in experimental models of ALS. By increasing VEGF levels, lithium would be helping prolong life in patients with ALS by protecting the brain from the disease.
The team sought to determine how lithium helped the brain recover from a stroke. They knew the pathways lithium targets in the body.
They found that lithium promotes the production of growth factors in the cells along the blood-brain barrier, which may explain how lithium repairs damaged blood vessels after a stroke.
Lithium has been used as a treatment for a number of mood disorders, most notably bipolar disorder. Only recently has lithium appeared to be useful for non-psychiatric central nervous system disorders, such as strokes and Lou Gehrig's disease (ALS).
However, the typical dose of lithium used for treatment is only slightly below the toxic dose, so there is a high risk of overdosing.
If the mechanism by which lithium acts to help treat strokes or ALS were known, then scientists could develop less-toxic medications designed to use the same mechanism as lithium to treat those conditions.
Previous studies had shown that two proteins, brain-derived neutrophin factor (BDNF) and vascular endothelial growth factor (VEGF), contribute to repairing the blood vessels leading to the brain that are damaged in a stroke. Lithium improved recovery times after strokes in rats.
The experiment involved developing cultures of rat brain cells, then adding lithium, and finally measuring the change in BDNF & VEGF levels over time. BDNF levels did not change; however, exposure to lithium caused VEGF levels to increase to as much as quadruple initial VEGF levels.
To determine which pathway lithium uses, synthetic inhibitors of the pathways lithium targets in the body were added to rat brain cells, and the results were compared to what was found when the cells were exposed to lithium.
One pathway, the inhibition of a protein called glycogen synthase kinase-3, has been previously shown to regulate VEGF levels. The team showed that lithium uses this pathway to increase VEGF levels, and thus, speed up repair of damaged tissue.
The effect of lithium on VEGF levels may explain the recent discovery that lithium may improve survival in patients suffering from ALS. VEGF has been proposed to help protect neurons in experimental models of ALS. By increasing VEGF levels, lithium would be helping prolong life in patients with ALS by protecting the brain from the disease.
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