ArticleTheranostics2026
Focused ultrasound-mediated blood-brain barrier modulation is associated with adult hippocampal neurogenic responses linked to zinc-dependent signaling.
Article in Theranostics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Rationale: Transcranial focused ultrasound (FUS)-mediated blood-brain barrier (BBB) modulation is a promising non-invasive therapeutic strategy for targeted brain drug delivery. However, its direct regenerative potential to actively remodel the brain microenvironment and promote adult hippocampal neurogenesis remains largely unexplored owing to elusive molecular mediators. Here, we investigated whether zinc-dependent signaling contributes to adult hippocampal neurogenic responses following FUS-mediated BBB modulation. Methods: We integrated pharmacological and genetic approaches in adult rodent models subjected to hippocampal-targeted low-intensity FUS with microbubbles. Neural progenitor proliferation and differentiation were quantified using BrdU and DCX labeling. To assess the contributions of extracellular/labile zinc availability and ZnT3-associated vesicular zinc physiology, intracerebroventricular zinc chelation with CaEDTA was performed in rats, and ZnT3 Results: FUS-mediated BBB modulation significantly increased dentate gyrus progenitor proliferation, neuroblast abundance, and newborn neuron survival. These effects were markedly attenuated by acute zinc chelation and were not observed in ZnT3 Conclusions: Our findings support a framework in which intact zinc availability, including ZnT3-associated zinc physiology, contributes to adult hippocampal neurogenic responses following FUS-mediated BBB modulation. This work provides a mechanistic framework for the development of ultrasound-guided therapeutic strategies aimed at promoting repair-associated plasticity in neurological disorders.
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