Multidimensional dynamic optical imaging unveils anesthetic-driven hemispheric lateralization in blood-brain barrier homeostasis

The blood-brain barrier (BBB) is commonly known to be distributed evenly within the central nervous system. This study elucidates previously unexplored physiological phenomena associated with the spatial heterogeneity of the BBB. We found that isoflurane facilitates hemispheric lateralization in BBB permeability, leading to different responses between the left and right hemispheres. To substantiate this finding, we used neural optical imaging to comprehensively map the spatial homeostasis of BBB. Image segmentation and feature extraction exhibited hemispheric lateralization in vascular microstructure and function. Gait analysis confirmed that the lateralization of BBB homeostasis influences behavioral functions. Our results indicate that the left hemisphere enhances its self-protective mechanisms by disrupting the balance of mitochondrial fission and fusion, resulting in structural changes in mitochondria and reduced ATP (adenosine 5′-triphosphate) production, which are crucial for maintaining BBB homeostasis. This study offers insights into the molecular pathways that regulate BBB integrity and their potential implications for drug delivery.