Metabolomic Profile of Cerebral Tissue After Blood-Brain Barrier Opening using Microbubble-Assisted Ultrasound: A Focus on Contralateral Side.

Microbubble (MB)-assisted ultrasound (US) is an innovative modality for the non-invasive, targeted and efficient delivery of the therapeutic molecules into the brain. Previously, we reported the first metabolomic signature of blood-brain barrier opening (BBBO) induced by MB-assisted US. In the present study, the neurometabolic consequences of acoustically mediated BBBO on cerebral tissue using multimodal metabolomics approaches. Sinusoid US waves (1 MHz, peak negative pressure 0.6 MPa, burst length 10 ms, total treatment time 30 s, MB bolus dose 0.7 10⁵ MBs/g) were applied on the right striatum (ipsilateral side). Brain was collected and both striata were then dissected 3 h, 2 days and 1 week after BBBO.  After tissue preparation, the samples were analyzed using nuclear magnetic resonance spectrometry (NMRS) and high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Our findings showed a slight disruption of metabolic pathways in contralateral striata of animals. Analyses of metabolic pathways indicated change of amino acid metabolisms. In addition, tryptophan derivate dosages revealed the perturbation of a central metabolite of the kynurenin pathway (i.e., 3-hydroxykynurenin). In conclusion, the acoustically mediated BBBO of the ipsilateral cerebral hemisphere induced significant change in metabolism of contralateral one.