Pharmacological investigation of roles of cyclic flow reductions in the development of cerebral infarction

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Animal models in which cyclic flow reductions are reproducibly observed have been not reported. Therefore, we tried to establish a new model with cyclic flow reductions in cerebral circulation. We establish the model using photochemical thrombosis technique, which has been developed in our institute. Using this model, we investigated roles of cyclic flow reductions in the development of cerebral infarction. Antithrombotic agents and thrombolytic agents have fetal side effects of cerebral hemorrhage. However, mechanisms of cerebral hemorrhage is still unclear and the predict is impossible. Although cyclic flow reductions are thought to contribute to cerebral hemorrhage, the mechanisms is unclear. Therefore, we investigated by what mechanisms heparin, an antithrombotic agent causes cerebral hemorrhage. In the rabbit cerebral thrombosis model, heparin caused cerebral hemorrhage and then worsen neurological symptoms. A radical scavenger inhibited cerebral hemorrhage produced by heparin and reduced cerebral infarct size. Based on these findings, free radical may play a key role in cerebral hemorrhage. Although free radical may damage vessel wall and then cause cerebral hemorrhage, further investigate may be required.