Stroke: New approach to treatment

Blood vessels that supply the brain with vital oxygen are suddenly blocked by blood clots; this causes nerve cells to die, and the sufferer develops symptoms that include paralysis and speech disorders: this is the typical scenario for a stroke.

At this point, rapid action is needed: The sooner the blood clots are dissolved with medication, the less severe the consequential damage is for the sufferer as a rule. Yet, often patients reach a life-saving hospital too late. This delay is also one reason why the risk of dying from a stroke in Germany is around ten times higher than the danger of being injured in a traffic accident.

Excess pressure inside the skull

However, this lack of oxygen inside the brain is only one issue among many that can occur with a stroke. One dreaded side effect, for example, are inflammatory processes in the brain and water retention in the nervous tissue, which is known as cerebral edema formation. Since the brain is surrounded by a rigid cranial bone, excess pressure builds up inside the skull, initially affecting healthy brain tissue at the same time.

“There are many facets to a stroke. It is this that makes it so difficult to treat; after all, most drugs can only target one key area,” says Professor Christoph Kleinschnitz, head of the Stroke Unit at the University of Würzburg’s Department of Neurology.

Publication in the “Annals of Neurology”

This shortage of effective medications might very soon be a thing of the past, hopes the neurologist. Kleinschnitz and his team have succeeded in inhibiting a specific inflammatory protein and, in so doing, noticeably reducing the consequences of a stroke.

They were supported in this by the Würzburg biomedical scientist Professor Bernhard Nieswandt and neurologists from the University of Münster. The researchers present the results of their work in the online issue of the “Annals of Neurology”, the official journal of the American Neurological Association.

“It has been known for quite some time that the inflammatory protein plasma kallikrein damages the nervous tissue in several ways after a stroke,” explains Kleinschnitz. For instance, this protein contributes to the creation of further blood clots in the brain. It also intensifies the inflammation as well as cerebral edema.

So, as a first step, the scientists worked with mice that lacked the gene for plasma kallikrein. These animals developed dramatically smaller strokes and revealed fewer neurological deficiencies. “This observation was very promising but it initially had no relevance to usage on patients. We therefore had to find a way of inhibiting plasma kallikrein pharmacologically as well,” explains Dr. Eva Göb, a research associate on Kleinschnitz’s team.

Antibody is effective even hours later

For this reason, the Würzburg researchers used an antibody that annuls the effect of plasma kallikrein in the blood of the mice. As they were able to show, this method also mitigated the consequences of a stroke dramatically. “What is interesting here is that the antibody itself was still effective when it was injected into the animals with a delay of three hours after the onset of the stroke. This means that the antibody could possibly be used on stroke patients who are late arriving at a hospital,” says Kleinschnitz. However, further studies and a safety test need to be conducted first before that point is reached.

The work in Würzburg Collaborative Research Center (SFB) 688 was funded by the German Research Foundation (DFG).

“Blocking of plasma kallikrein ameliorates stroke by reducing thromboinflammation” Eva Göb, Stephan Reymann, Friederike Langhauser, Michael K. Schuhmann, Peter Kraft, Ina Thielmann, Kerstin Göbel, Marc Brede, György Homola, László Solymosi, Guido Stoll, Christian Geis, Sven G. Meuth, Bernhard Nieswandt, Christoph Kleinschnitz. Annals of Neurology. Published online on January 27, 2015. doi: 10.1002/ana.24380.

Contact

Prof. Dr. Christoph Kleinschnitz, Department of Neurology at the University of Würzburg, T +49 (0)931 201-23756, christoph.kleinschnitz@uni-wuerzburg.de