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Multimodal analysis of aged wild-type mice exposed to repeated scanning ultrasound treatments demonstrates long-term safety2.04 MB
Published VersionCC BY-NC V4.0, Open Access
Journal article
Multimodal analysis of aged wild-type mice exposed to repeated scanning ultrasound treatments demonstrates long-term safety
Theranostics, Vol.8(22), pp.6233-6247
2018
PMCID: PMC6299703
PMID: 30613294
Abstract
The blood-brain barrier presents a major challenge for the delivery of therapeutic agents to the brain; however, it can be transiently opened by combining low intensity ultrasound with microbubble infusion. Studies evaluating this technology have largely been performed in rodents, including models of neurological conditions. However, despite promising outcomes in terms of drug delivery and the amelioration of neurological impairments, the potential for long-term adverse effects presents a major concern in the context of clinical applications.
To fill this gap, we repeatedly treated 12-month-old wild-type mice with ultrasound, followed by a multimodal analysis for up to 18 months of age.
We found that spatial memory in these aged mice was not adversely affected as assessed in the active place avoidance test. Sholl analysis of Golgi impregnations in the dentate gyrus of the hippocampus did not reveal any changes to the neuronal cytoarchitecture. Long-term potentiation, a cellular correlate of memory, was still achievable, magnetic resonance spectroscopy revealed no major changes in metabolites, and diffusion tensor imaging revealed normal microstructure and tissue integrity in the hippocampus. More specifically, all measures of diffusion appeared to support a neuroprotective effect of ultrasound treatment on the brain.
This multimodal analysis indicates that therapeutic ultrasound for blood-brain barrier opening is safe and potentially protective in the long-term, underscoring its validity as a potential treatment modality for diseases of the brain.
Details
- Title
- Multimodal analysis of aged wild-type mice exposed to repeated scanning ultrasound treatments demonstrates long-term safety
- Authors
- Daniel G Blackmore (Author) - The University of QueenslandFabrice Turpin (Author) - The University of QueenslandAbdalla Z Mohamed (Author) - The University of QueenslandFangrong Zong (Author) - The University of QueenslandRucha Pandit (Author) - The University of QueenslandMatthew Pelekanos (Author) - The University of QueenslandFatima Nasrallah (Author) - The University of QueenslandPankaj Sah (Author) - The University of QueenslandPerry F Bartlett (Author) - The University of QueenslandJürgen Götz (Author) - The University of Queensland
- Publication details
- Theranostics, Vol.8(22), pp.6233-6247
- Publisher
- Ivyspring International Publisher
- Date published
- 2018
- DOI
- 10.7150/thno.27941
- ISSN
- 1838-7640
- PMID
- 30613294; PMC6299703
- Organisation Unit
- University of the Sunshine Coast, Queensland; Thompson Institute
- Language
- English
- Record Identifier
- 99525808002621
- Output Type
- Journal article
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