How does CO2 affect brain function - and what role do blood vessels play in this?

Scientists, led by CBBM members Jan Wenzel and Markus Schwaninger from the Institute for Experimental and Clinical Pharmacology and Toxicology, have been working on this question. In a study that has just been published in the scientific journal "Proceedings of the National Academy of Sciences (PNAS)", they investigated the effect of an increased COconcentration on behavior and respiration when the blood flow in the brain is disturbed.

In the normal metabolism of the body, CO2 is constantly produced by cells. CO2 occurs in elevated concentrations in the brain when it is either produced in increased amounts or inefficiently washed out of the brain. It is transported from the organs to the lungs via the blood. To facilitate removal, CO2 significantly increases the blood flow in the brain, a reaction that is disrupted in many diseases such as high blood pressure, diabetes or obesity.

The researchers first found out how CO2 increases blood flow. A special signaling pathway in endothelial cells of the vessels is crucial for this. Interestingly, the reduced reactivity of the blood vessels to CO2 had significant consequences for the behavior of the animals. The research group observed that an impaired vascular response to CO2, which occurs in many patients with vascular diseases, led to anxious behavior and irregular breathing in the mice.

The study, that was carried out together with colleagues from Hamburg, Borstel, Bonn, Berlin, Mannheim, and Zurich, may provide the basis for new therapies for the treatment of vascular diseases in the brain. In the near future, the researchers plan to test initial therapeutic approaches in the laboratory and transfer their findings to humans.


Wenzel, J., Hansen, C.E., Bettoni, C., Vogt, M.A.., Lembrich, B., Natsagdorj, R., Huber, G., Brands, J., Schmidt, K., Assmann, J.C., Stölting, I., Saar, K., Sedlacik, J., Fiehler, J., Ludewig, P., Wegmann, M., Feller, N., Richter, M., Müller-Fielitz, H., Walther, T., König, G.M., Kostenis, E., Raasch, W., Hübner, N., Gass, P., Offermanns, S., de Wit, C., Wagner, C.A., and Schwaninger, M. (2020) „Impaired endothelium-mediated cerebrovascular reactivity promotes anxiety and respiration disorders in mice” PNAS January 21, 2020 117 (3) 1753-176, 2020


The mRNA expression of a pH receptor (Gpr4), which plays an essential role in the CO2-induced blood flow response, in a vessel of the brain (collagen IV-positive) is shown. The expression is located to endothelial cells verified by costaining against the marker Pecam. Cell nuclei are indicated by DAPI.