Article Dans Une Revue Theranostics Année : 2024

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

Résumé

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.

Fichier principal
Vignette du fichier
v14p4147.pdf (6.68 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
Licence

Dates et versions

hal-04634511 , version 1 (04-07-2024)

Licence

Identifiants

Citer

Sébastien Rigollet, Claire Rome, Thomas Ador, Erik Dumont, Chantal Pichon, et al.. FUS-mediated BBB opening leads to transient perfusion decrease and inflammation without acute or chronic brain lesion. Theranostics, 2024, 14 (10), pp.4147-4160. ⟨10.7150/thno.96721⟩. ⟨hal-04634511⟩
121 Consultations
180 Téléchargements

Altmetric

Partager

  • More