Article
Occurrence of Spreading depolarization and impact on delayed infarct progression after malignant hemispheric stroke in C57/bl6 mice
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Published: | June 9, 2017 |
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Objective: Spreading depolarization (SD) occurs in high frequency in patients with malignant hemispheric stroke (MHS) and is coupled either to hyperaemic or hypoaemic blood flow responses. After experimental focal ischaemia SD is a significant cause for secondary stroke progression during the initial period of infarct maturation. Due to the need of surgery SD is typically monitored 48 to 120 hours after stroke onset under clinical conditions. Currently it is not known by what extent SD contributes to stroke progression during this delayed period. In this current study we analyze neurovascular coupling and occurrence of SD in a later phase of experimental cerebral ischemia.
Methods: Permanent focal ischemia was induced by distal occlusion of the left middle cerebral artery in male C57/bl6 mice. 24h after MCA occlusion, spreading depolarization was induced with potassium chloride. The neurovascular response was measured by laser speckle contrast analysis. Infarct progression was evaluated by sequential MRI. Three study groups were analyzed: control group without SD induction, SD induction with potassium chloride and SD induction and Ketamine administration (25 mg/kg body weight i.p.).
Results: 24 hours after stroke onset we observed 0.2 ± 0.2 SD/hour. The mean duration was 1.6 ± 1.0 minutes. During potassium application the frequency and duration increased to 3.3 ± 0.7 SD/hour and 3.2 ± 3.5 minutes, respectively. Ketamin treatment reduced the number and duration to 2.4 ± 0.8 SD/hour and 1.36 ± 0.95 minutes, respectively. Neurovascular coupling was dependent on the distance from the ischemic region but did not differ between individual groups. Induction of SD significantly increased stroke volume even 24 hours after stroke onset, which could be prevented by additional ketamine treatment.
Conclusion: Induction of SD with potassium was significantly associated with stroke progression even 24 hours after stroke onset. Therefore, SD might be a significant contributor for delayed stroke progression. Ketamine might be a possible drug to prevent SD induced stroke progression.