Endogenous Neural Stem Cell Activation after Low-Intensity Focused Ultrasound-Induced Blood–Brain Barrier Modulation

Abstract

Endogenous neural stem cells (eNSCs) in the adult brain, which have the potential to self-renew and differentiate into functional, tissue-appropriate cell types, have raised new expectations for neurological disease therapy. Low-intensity focused ultrasound (LIFUS)-induced blood–brain barrier modulation has been reported to promote neurogenesis. Although these studies have reported improved behavioral performance and enhanced expression of brain biomarkers after LIFUS, indicating increased neurogenesis, the precise mechanism remains unclear. In this study, we evaluated eNSC activation as a mechanism for neurogenesis after LIFUS-induced blood–brain barrier modulation. We evaluated the specific eNSC markers, Sox-2 and nestin, to confirm the activation of eNSCs. We also performed 3′-deoxy-3′[18F] fluoro-L-thymidine positron emission tomography ([18F] FLT-PET) to evaluate the activation of eNSCs. The expression of Sox-2 and nestin was significantly upregulated 1 week after LIFUS. After 1 week, the upregulated expression decreased sequentially; after 4 weeks, the upregulated expression returned to that of the control group. [18F] FLT-PET images also showed higher stem cell activity after 1 week. The results of this study indicated that LIFUS could activate eNSCs and induce adult neurogenesis. These results show that LIFUS may be useful as an effective treatment for patients with neurological damage or neurological disorders in clinical settings.

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

“…And recently sonodynamic therapy, a combination of LIUS with a chemotherapeutic agent (sonosensitizer) has been explored as a promising alternative to cancer therapies [ 28 ]. In the field of stem cell research, LIPU promotes the expansion, differentiation, and migration of mesenchymal stem cells [ 29 , 30 ], and it has been reported that LIFU-induced BBB regulation can promote neurogenesis through the activation of endogenous neural stem cells [ 31 ]. In addition, LIPU can produce different biological effects on organs, tissues, and cells, and can be applied in fracture healing, cartilage repair [ 32 ], periodontal tissue regeneration [ 33 ], and alveolar bone regeneration [ 34 ].…”