Real-time MRI guidance for reproducible hyperosmolar opening of the blood-brain barrier in mice

Chengyan Chu, Guanshu Liu, Miroslaw Janowski, Jeff W Bulte, Shen Li, Monica Pearl, Piotr Walczak

Research output: Contribution to journalArticle

Abstract

The blood-brain barrier (BBB) prevents effective delivery of most therapeutic agents to the brain. Intra-arterial (IA) infusion of hyperosmotic mannitol has been widely used to open the BBB and improve parenchymal targeting, but the extent of BBB disruption has varied widely with therapeutic outcomes often being unpredictable. In this work, we show that real-time MRI can enable fine-tuning of the infusion rate to adjust and predict effective and local brain perfusion in mice, and thereby can be allowed for achieving the targeted and localized BBB opening (BBBO). Both the reproducibility and safety are validated by MRI and histology. The reliable and reproducible BBBO we developed in mice will allow cost-effective studies on the biology of the BBB and drug delivery to the brain. In addition, the IA route for BBBO also permits subsequent IA delivery of a specific drug during the same procedure and obtains high targeting efficiency of the therapeutic agent in the targeted tissue, which has great potential for future clinical translation in neuro-oncology, regenerative medicine and other neurological applications.

Original languageEnglish (US)
JournalFrontiers in Neurology
Volume9
Issue numberOCT
DOIs
StatePublished - Oct 26 2018

Fingerprint

Blood-Brain Barrier
Brain
Intra Arterial Infusions
Regenerative Medicine
Mannitol
Pharmaceutical Preparations
Histology
Therapeutics
Perfusion
Safety
Costs and Cost Analysis

Keywords

  • Blood brain barrier
  • Intra-arterial
  • Mannitol
  • Mouse model
  • MRI

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Real-time MRI guidance for reproducible hyperosmolar opening of the blood-brain barrier in mice. / Chu, Chengyan; Liu, Guanshu; Janowski, Miroslaw; Bulte, Jeff W; Li, Shen; Pearl, Monica; Walczak, Piotr.

In: Frontiers in Neurology, Vol. 9, No. OCT, 26.10.2018.

Research output: Contribution to journalArticle

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