Kurzfassung

Stroke is a leading cause of death and long-term disability in industrialized countries. Excessive production of reactive oxygen species (ROS) is believed to be one of the mechanisms taking part in the neuronal damage in stroke. ROS can be produced by several enzyme systems, with NADPH oxidases being a major source. Recently, several homologues of gp91phox (now termed Nox2) have been cloned. These include Nox1, Nox3, Nox4 and Nox5. Because Nox3 is mainly expressed in inner ear and Nox5 only...Stroke is a leading cause of death and long-term disability in industrialized countries. Excessive production of reactive oxygen species (ROS) is believed to be one of the mechanisms taking part in the neuronal damage in stroke. ROS can be produced by several enzyme systems, with NADPH oxidases being a major source. Recently, several homologues of gp91phox (now termed Nox2) have been cloned. These include Nox1, Nox3, Nox4 and Nox5. Because Nox3 is mainly expressed in inner ear and Nox5 only found in human tissues but not in rodents, we do not include Nox3 and Nox5 in our work. Mice lacking Nox2 are protected against brain ischemia/reperfusion injury, indicating that Nox2 is involved in the development of neuronal damage following ischemic stroke. The roles of Nox1 and Nox4 in this scenario, however, are yet unknown.
Therefore, the present project deals with the following central issues:
(1) spatiotemporal expression pattern of Nox enzymes in mouse brain after stroke (induced by middle cerebral artery occlusion);
(2) role of Nox1 and Nox4 in ischemic stroke;
(3) therapeutic potential of Nox-suppressing compounds in experimental stroke.
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