A team of researchers has developed a therapeutic technique that dramatically increases the production of nerve cells in mice with stroke-induced brain damage. The therapy relies on the combination of two methods that show promise as treatments for stroke-induced neurological injury. The first consists of surgically grafting human neural stem cells into the damaged area, where they mature into neurons and other brain cells. The second involves administering a compound called 3K3A-APC, which the scientists have shown helps neural stem cells grown in a petri dish develop into neurons. However, it was unclear what effect the molecule, derived from a human protein called activated protein-C (APC), would have in live animals.
A month after their strokes, mice that had received both the stem cells and 3K3A-APC performed significantly better on tests of motor and sensory functions compared to mice that received neither or only one of the treatments. In addition, many more of the stem cells survived and matured into neurons in the mice given 3K3A-APC. "This animal study could pave the way for a potential breakthrough in how we treat people who have experienced a stroke. If the therapy works in humans, it could markedly accelerate the recovery of these patients."
To confirm that the stem cells were responsible for the animals' improved function, the researchers used a targeted toxin to kill the neurons that had developed from them in another group of mice given the combination therapy. These mice showed the same improved performance on the tests of sensory and motor functions prior to being given the toxin but lost these gains afterwards, suggesting that the neurons that grew from the implanted cells were necessary for the improvements. In a separate experiment, the team examined the connections between the neurons that developed from the stem cells in the damaged brain region and nerve cells in a nearby region called the primary motor cortex. The mice given the stem cells and 3K3A-APC had many more neuronal connections, called synapses, linking these areas than mice given the placebo. In addition, when the team stimulated the mice's paws with a mechanical vibration, the neurons that grew from the stem cells responded much more strongly in the treated animals. "That means the transplanted cells are being functionally integrated into the host's brain after treatment with 3K3A-APC. No one in the stroke field has ever shown this, so I believe this is going to be the gold standard for future studies."