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FUS-mediated BBB opening leads to transient perfusion decrease and inflammation without acute or chronic brain lesion

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  • معلومة اضافية
    • Contributors:
      Image Guided Therapy (IGT); GIN Grenoble Institut des Neurosciences (GIN); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA); Université Grenoble Alpes (UGA); Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM); Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS); Université d'Orléans (UO); Centre Hospitalier Universitaire CHU Grenoble (CHUGA); IRMaGe (IRMaGe); Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA); ANR-11-INBS-0006,FLI,France Life Imaging(2011)
    • بيانات النشر:
      CCSD
      Ivyspring International Publisher
    • الموضوع:
      2024
    • Collection:
      Université d'Orléans: HAL
    • نبذة مختصرة :
      International audience ; Impact: The permeabilization of the BBB to deliver therapeutics with MR-guided FUS redefines therapeutic strategies as it improves patient outcomes. To ensure the best translation towards clinical treatment, the evaluation of hemodynamic modifications in the CNS is necessary to refine treatment parameters. Methods: MR-guided FUS was applied at 1.5 MHz with a 50 ms burst every 1 s to open the BBB. CBF, BVf and ADC parameters were monitored with MRI. Cavitation was monitored with a PCD during the FUS sequence and classified with the IUD index into three cavitation levels. We distinctly applied the FUS in the cortex or the striatum. After the BBB permeabilization, neuroinflammation markers were quantified longitudinally. Results: The BBB was successfully opened in all animals in this study and only one animal was classified as "hard" and excluded from the rest of the study. 30 min after FUS-induced BBB opening in the cortex, we measured a 54% drop in CBF and a 13% drop in BVf compared to the contralateral side. After permeabilization of the striatum, a 38% drop in CBF and a 15% drop in BVf were measured. CBF values rapidly returned to baseline, and 90 min after BBB opening, no significant differences were observed. We quantified the subsequent neuroinflammation, noting a significant increase in astrocytic recruitment at 2 days and microglial activation at 1 day after FUS. After 7 days, no more inflammation was visible in the brain. Conclusion: FUS-induced BBB opening transiently modifies hemodynamic parameters such as CBF and BVf, suggesting limited nutrients and oxygen supply to the CNS in the hour following the procedure.
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/38994025; PUBMED: 38994025; PUBMEDCENTRAL: PMC11234282
    • الرقم المعرف:
      10.7150/thno.96721
    • الدخول الالكتروني :
      https://hal.science/hal-04634511
      https://hal.science/hal-04634511v1/document
      https://hal.science/hal-04634511v1/file/v14p4147.pdf
      https://doi.org/10.7150/thno.96721
    • Rights:
      info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.7747C610