Temporal dynamics of neurovascular unit changes following blood-brain barrier opening in the putamen of non-human primates

• DOI: 10.1016/j.jconrel.2024.11.019
• Publication Date: 2024-11-18T04:43:13Z
• Authors: Tiziano Balzano; José A. Pineda-Pardo; Noelia Esteban-Ga...; Miguel López-Aguirre; Alejandro Reinare...; Inés Trigo-Damas; Masahiko Takada; José A. Obeso; Javier Blesa
• Keywords: Pericyte; Putamen

Low-intensity focused ultrasound (LIFU) combined with intravenously circulating microbubbles has recently emerged as a novel approach for increasing delivery through the blood-brain barrier (BBB). This technique safely and transiently enables therapeutic agents to overcome BBB, which typically poses significant obstacle treatment of brain disorders. However, full impact LIFU on entire neurovascular unit (NVU), well mechanisms factors involved in restoring BBB integrity still require further elucidation. We conducted immunohistochemical analyses putamen non-human primates monitor changes over time [immediately post-treatment (3 h) at 7- 30-days post-BBB opening] vascular, glial, immune cells. Additionally, we examined dynamic interactions among these elements their role restorative process level. A mild inflammatory response primarily involving microglia, astrocytes, T- B-lymphocytes was observed treated acutely after opening. These cells, recruited vascular changes, stimulate upregulation PDGFRβ, pericyte-specific marker, VEGF-A, pro-angiogenic factor. associated sprouting by 7 days Importantly, no notable long-term alterations were NVU 30 results offer evidence regarding efficacy safety achieving opening primate brain, indicating that nearly all revert baseline within post-treatment. also suggests angiogenesis may play an important