Strokes usually occur as follows: blood vessels that supply the brain with oxygen and other vital things suddenly become blocked by blood clots. This causes damage to the brain. Even if the clots are eliminated quickly, many people affected subsequently suffer neurological dysfunctions, such as major paralysis or speech disorders.
There are other factors that are also responsible for damage following a stroke, most notably inflammatory processes in the brain and the formation of a so-called cerebral edema, where fluid from the damaged blood vessels leaks into the brain tissue. Pressure builds as a result, so areas of the brain that were initially healthy can become affected as well.
“This multitude of harmful processes after a stroke is one reason why new treatments have often failed in the past,” says Professor Christoph Kleinschnitz, head of Stroke Medicine at the University of Würzburg’s Department of Neurology. Ideally, new medications should therefore target several key sites in order to achieve maximum effect.
Blood protein inhibition shows promise
Medicine could be closing in on this goal with inhibition of the blood protein kininogen since this damages nerve cells in three ways following a stroke: firstly, it promotes the formation of further blood clots in the brain; it also exacerbates both inflammation and cerebral edema. This is what Kleinschnitz’s team of Würzburg biophysicists and biomedical scientists is now reporting in the online issue of “Blood”, the renowned journal of the American Society of Hematology.
The scientists worked with mice that were lacking the gene for kininogen. The brain damage suffered by these animals following a stroke was reduced by more than two thirds. They also experienced far fewer neurological dysfunctions. “This protective effect lasted for many days and was observed in both young and old mice, in males as well as females,” says Kleinschnitz. This finding is hugely important, he explains, because gender-specific differences have often been neglected in stroke research.
Next step: use of antibodies
Next, the Würzburg researchers wish to inhibit the blood protein kininogen not just genetically, but also pharmacologically – with antibodies. This would be an important step on the road to assessing whether the new method might also be trialed in stroke patients at a later date.
The work in Würzburg Collaborative Research Center (SFB) 688 was funded by the German Research Foundation (DFG) as well as the Wilhelm Sander Foundation.
“Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain-barrier damage and inflammation”, Friederike Langhauser, Eva Göb, Peter Kraft, Christian Geis, Joachim Schmitt, Marc Brede, Kerstin Göbel, Xavier Helluy, Mirko Pham, Martin Bendszus, Peter Jakob, Guido Stoll, Sven G. Meuth, Bernhard Nieswandt, Keith R. McKrae, and Christoph Kleinschnitz. Blood, published online on August 30, 2012, DOI 10.1182/blood-2012-06-440057
Prof. Dr. Christoph Kleinschnitz, Department of Neurology at the University of Würzburg, T +49 (0)931 201-23756, firstname.lastname@example.org