Enhanced Delivery and Bioactivity of the Neurturin Neurotrophic Factor through Focused Ultrasound—Mediated Blood—Brain Barrier Opening in vivo

• DOI: 10.1038/jcbfm.2014.236
• Publication Date: 2015-01-14T08:56:43Z
• Authors: Gesthimani Samiotaki; Camilo Acosta; Shutao Wang; Elisa E Konofagou
• Keywords: Neurturin; Neuroregeneration

The blood—brain barrier (BBB) constitutes a major obstacle in brain drug delivery. Focused ultrasound (FUS) conjunction with microbubbles has been shown to open the BBB noninvasively, locally, and transiently allow large molecules diffusion. Neurturin (NTN), member of glial-derived neurotrophic factor (GDNF) family, demonstrated have neuroprotective regenerative effects on dopaminergic neurons vivo using invasive delivery methods. brain's ascending nigrostriatal pathway is severely damaged Parkinson's disease (PD), therefore substantia nigra (SN) striatal caudoputamen (CP) were selected as target areas. objective study was investigate whether safe efficient NTN can be achieved through FUS-induced opening via intravenous administration, thus trigger neuroregeneration cascade pathway. After optimization FUS parameters locations murine brain, bioavailability downstream signaling detected characterized immunostaining. significantly enhanced compared direct injection technique, whereas triggering neuronal nuclei. These findings indicate potential method mediate transport proteins PD animal model.