Every year, around 200,000 people in Germany and 1 million people in Europe suffer from stroke. It happens when blood clots block the major vessels and there is not enough blood left in the brain. If doctors can break down or mechanically remove the clot, further damage is avoided.
However, 100 percent of the initially affected tissue and about 70 percent of cells in adjacent areas die. Scientists based at LMU Medical Center, Charité Berlin and the University of Maryland, Baltimore (USA), led by Dr Francisco Pan-Montojo (Clinic for Psychiatry and Psychotherapy at the University of Munich) have now been able to demonstrate in several relevant animal models of stroke that glycolic acid can be used successfully to save endangered tissue. Experimental treatment mimics a nematode survival strategy Caenorhabditis elegans a worm present in the soil, as reported by researchers in Advanced sciences.
Survival strategies C. elegans
The nematode C. elegans can even endure desiccation by entering a special larval stage called dauer. Its metabolism stops when the worm dries up and reactivates on contact with water. Both situations lead to a stress response with a huge increase in the production of reactive molecules (radicals), increased levels of calcium in nerve cells, and functional changes in mitochondria, the cell organelles that generate energy. The fact that C. elegans survives, this is mainly due to its ability to increase the production of glycolic acid in its cells during desiccation, as experimental studies have shown: when the production of glycolic acid is inhibited, it dies, while the Glycolic acid supplied externally has a protective effect allowing the worms to survive.
Good protection in animal models
In strokes we see processes similar to those that take place in the desiccation and rehydration of C. elegans.“
Dr Francisco Pan-Montojo, Clinic for Psychiatry and Psychotherapy, University Hospital of Munich
Therefore, the researchers investigated the hypothesis that glycolic acid could be used in mammals to reduce secondary damage resulting from a stroke. Indeed, experiments in various in vitro models and representative animals of stroke have shown that up to 100 percent of all nerve cells can be protected after administration of the molecule. The size of the affected region has also decreased. “We were able to demonstrate that the protective effect of glycolic acid is primarily based on combating stroke-dependent calcium increases in cells,” explains Pan-Montojo. “Our results indicate that treatment with glycolic acid has the potential to reduce mortality and disability in stroke patients.” With colleagues, Pan-Montojo founded a start-up with the aim of moving from research to application in patients.
Ludwig-Maximilians-Universitaet Muenchen (LMU)
Chovsepian, A., et al. (2021) A primordial glycolic acid-based desiccation tolerance mechanism saves mammalian neurons from ischemia by reducing intracellular calcium-mediated excitotoxicity. Advanced sciences. doi.org/10.1002/advs.202103265.