Low intensity focused ultrasound: a new prospect for the treatment of Parkinson's disease.

As a chronic and progressive neurodegenerative disease, Parkinson's disease (PD) still lacks effective and safe targeted drug therapy. Low-intensity focused ultrasound (LIFU), a new method to stimulate the brain and open the blood-brain barrier (BBB), has been widely concerned by PD researchers due to its non-invasive characteristics. PubMed was searched for the past 10 years using the terms 'focused ultrasound', 'transcranial ultrasound', 'pulse ultrasound', and 'Parkinson's disease'. Relevant citations were selected from the authors' references. After excluding articles describing high-intensity focused ultrasound or non-Parkinson's disease applications, we found more than 100 full-text analyses for pooled analysis. Current preclinical studies have shown that LIFU could improve PD motor symptoms by regulating microglia activation, increasing neurotrophic factors, reducing oxidative stress, and promoting nerve repair and regeneration, while LIFU combined with microbubbles (MBs) can promote drugs to cross the BBB, which may become a new direction of PD treatment. Therefore, finding an efficient drug carrier system is the top priority of applying LIFU with MBs to deliver drugs. This article aims to review neuro-modulatory effect of LIFU and the possible biophysical mechanism in the treatment of PD, summarize the latest progress in delivering vehicles with MBs, and discuss its advantages and limitations.