Conclusion
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.
Methods
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.
Results
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.