Real-time monitoring of spatial and temporal metabolic changes during focal cerebral ischemia in rats

Focal cerebral ischemia creates a gradual injury, ranging from severe injury in the core towards moderate damage in the penumbra. Disruption of blood supply leads to shortage in oxygen supply, resulting in mitochondrial disruption in the ischemic area. The present work study the mitochondrial function and microcirculatory blood supply in the core and penumbra of the ischemic tissue following different ischemic durations. Focal ischemia was obtained by middle cerebral artery occlusion (MCAO). Monitoring of the brain was conducted using a unique multi-site–multi-parametric (MSMP) monitoring system, which enables real-time, in vivo, simultaneous and continuous monitoring of mitochondrial NADH and CBF. Short sessions of anoxia before ischemia and following reperfusion were used to test the ability of the tissue to respond to such metabolic challenges. Following focal ischemia, CBF levels decreased and NADH levels increased and recovered at reperfusion. These changes were more severe in the core compared to the penumbra. Longer ischemic duration led to an increase in oxygen demand following reperfusion and to vast disruption of blood supply, as seen during short anoxic exposures. In conclusion, the ability of mitochondrial activity and blood supply to recuperate following ischemia, as well as the ability of the tissue to cope with metabolic challenges, varies in the core and the penumbra and depends on ischemic duration. The MSMP monitoring system, used in the current study, can add valuable information regarding the metabolic state of the brain during focal ischemia.

Research highlights
► Mitochondrial damage increase as blood flow decrease and recuperate at reperfusion.
► Mitochondrial recuperation depends on cerebral location and ischemic duration.
► Coping with metabolic challenges depends on intensity and duration of ischemia.