Abstract TP235: Temporal Change Of Brain Mitochondrial Function In A Rodent Model Of Subarachnoid Hemorrhage

Abstract

Introduction: Subarachnoid hemorrhage (SAH) is a devastating disease. A third of the patients die and a large percentage of the survivors require support in daily living and suffers from reduced quality of life. As part of clinical practice for these patients, a cerebral microdialysis catheter may be placed to monitor cerebral metabolic function. Using this monitoring technique, the patients often demonstrate an increase in the lactate-pyruvate ratio, despite adequate supply of glucose and oxygen, which may be an indirect marker of mitochondrial dysfunction. We wanted to identify a possible mitochondrial dysfunction in a rat SAH model at different time points by directly measuring mitochondrial function in brain tissue ex vivo . Method: The pre-chiasmatic single injection model of SAH was used. Oroboros Oxygraph high resolution respirometry was used to evaluate the electron transport chain of the mitochondria. We also analyzed ROS generation simultaneously at the same time points using the Oroboros LED2 module. We measured tissue from the cortex and the hippocampus. Results: 45 rats at four different timepoints, 6-, 24-, 48- and 96 hours after surgery, were included. We identified a significant reduction in respiration through complexes I and II of the electron transport chain in hippocampal tissue at 96 hours after SAH compared to sham. The respiration of cortical tissue at the same time point was reduced compared to sham but did not reach significance. No differences were identified at other time points and no differences in ROS generation were identified. Conclusion: We conclude that the SAH model can be used as a suitable model to identify mitochondrial dysfunction and that the respiratory capacity of the electron transport chain is reduced in the hippocampus at 96 h post insult in this rat model of SAH.