How to protect nerve cells in a stroke

A circulatory disturbance in the brain threatens with a stroke: little blood comes to neurons, they lack oxygen and nutrients, and as a result, nerve cells die in large numbers. But among them there are those who were very lacking in oxygen and who die immediately, but there are those who die gradually, within hours and even days after the “main” stroke.

These neurons, which do not die immediately, are in the so-called ischemic penumbra: the problem with oxygen is not so acute at all, and in principle they could survive (especially since restoration processes are included in the nervous tissue). However, the initial stress is too strong, and the processes that lead to its death are included in the cell.

If these processes are stopped, many neurons can be saved. Researchers from University of Pittsburgh previously showed that the unnecessary death of neurons during a stroke is associated with the outflow of potassium ions from them. Without potassium ions, neurons will not be able to generate impulses (not to mention other functions of potassium in the cell), and these ions constantly enter and exit neurons through special protein channels in the cell membrane. But in “near-stroke” neurons, potassium leaves too much of the cells, which is why the program of cell death is activated: the neuron considers itself incapable of performing functions, and in such cases the cell must die.

The loss of potassium is associated with the interaction of two neural proteins: one is the ion channel itself, which is built into the membrane, the second is the syntaxin protein, which also sits in the membrane and ensures the functioning of interneuronal synapses. If you do not allow these two proteins to interact, you can protect neurons from unnecessary death.

However, as further experiments continued, new details were discovered here. In the article in Science Advances it is said that normally the ion channels for potassium are grouped in the membrane. If the neuron feels harm, then additional channel molecules join the cluster of potassium ion channels – the protein syntaxin delivers them here. Moreover, syntaxin embeds new channel molecules just because the channels initially sit in the membrane by a cluster, a group. And now, through an expanded group, potassium ions leave the cell in a wide stream.

The researchers created a small protein called TAT-DP-2, which interferes with this: it destroys the cluster of ion channels on the membrane – their molecules diverge from each other, and now, since there is no group, syntaxine no longer implements potassium channels in the membrane. As a result, the cell remains with potassium, and the cell death program does not start.

The TAT-DP-2 protein was tested in mice with an experimental stroke, and indeed they had much fewer neurons dying, and brain functions were better preserved than in mice that did not receive TAT-DP-2. This protein could be a means of significantly mitigating the effects of a stroke, especially when a person cannot be quickly taken to a hospital; but his medical prospects will become clearer only after clinical research.