Brain Signal Determines Stroke Outcome

specific signal in brain cells may determine whether stroke patients live or die, suggesting that new therapies for stroke victims could be developed by controlling the signaling pathway, according to a new study published in the November 13, 2005, online issue of Nature Medicine.

Scientists at the University of Heidelberg (Germany) discovered that damaged and dying brain cells are using an internal "communications network” known as the NF-kB signaling pathway. Evidence in nerve cells had suggested this pathway could trigger apoptosis. To clarify the function of the pathway, the scientists developed a "conditional knockout” mouse with a stroke-like condition in which a protein called IKK2 activated the pathway. This allowed them to shut down the NF-kB molecule at any time in neurons. Meanwhile, another group of investigators at the University of Ulm (Germany), working in parallel, had generated two additional mouse models that allowed the reversible repression or activation of IKK2 at any time in neurons.

By combining their findings, the researchers were able to obtain a clear picture of IKKs's role after a stroke. Mice with the hyperactive form of IKK2 in neurons and too much NF-kB signaling suffer more damage than normal and far more cells die. However, if the IKK2 signal is blocked, damaged cells stay alive and appear to recover even when the blocking is done a few hours after the stroke. Moreover, the effects are long-term: neurons in the damaged tissues were still alive several days after the stroke.

"The unique advantage of this system is that we can specifically induce or block this signaling pathway at virtually any time and selectively in neurons,” said Thomas Wirth, University of Ulm. He noted that the same effects could be achieved by blocking the IKK2 pathway with a small artificial molecule, which is what a drug would have to do.