In a new study, researchers have identified a novel drug that could protect the brain during and after a stroke.
They found that injured neurons can remain viable if they are prevented from following biochemical pathways that lead to cell death.
The research was conducted by neuroscientists at the University of Pittsburgh Brain Institute.
A stroke occurs because a clot clogs a brain blood vessel, blocking blood and oxygen from reaching neurons and killing them.
Nearby neurons, in an area called the stroke penumbra, also can become dysfunctional and die hours or days later, even when their blood and oxygen supply was only mildly or transiently reduced.
No drugs exist in clinical practice that is capable of blocking the cell death that occurs following stroke.
If researchers can find ways to prevent these neurons from dying, recovery might be improved, and doctors might be able to better help people who have strokes in which the clot is in an inaccessible blood vessel or who could not get to the hospital in time for early intervention.
In previously published studies, the team showed that the interaction between a potassium channel in the cell membrane called Kv2.1 and a protein called syntaxin encouraged potassium ions to leak out of the neuron, triggering cell death.
And they found that using an experimental compound called TAT-C1aB could prevent cell death by interfering with the interaction of syntaxin and Kv2.1.
For this new study, the researchers identified two types of Kv2.1 channels in the neuronal cell membrane.
One channel is routinely involved in cell excitability, while the other allows entry of additional, new Kv2.1 channels into the membrane, promoting the release of potassium and ultimately neuronal cell death.
Armed with this knowledge, the scientists created a new small protein called TAT-DP-2 that disrupts the passage of these new channels into the cell membrane, keeping potassium in the cell and halting the biochemical pathway for cell death.
Mice that received an injection of TAT-DP-2 after a stroke had smaller areas of stroke damage and their long-term neurological function was better than that of untreated animals.
The team says two completely different approaches involving Kv2.1 led to better stroke outcomes, indicating the promise of neuroprotective drugs that target the channel.
One author of the study is Anthony Schulien, a medical student in Pitt’s Physician Scientist Training Program.
The study is published in Science Advances.
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