Abstract
BackgroundThe blood-cerebrospinal fluid (CSF) barrier (BCSFB) is critically important to the pathophysiology of the central nervous system (CNS). However, this barrier prevents the safe transmission of beneficial drugs from the blood to the CSF and thus the spinal cord and brain, limiting their effectiveness in treating a variety of CNS diseases.MethodsThis study demonstrates a method on SD rats for reversible and site-specific opening of the BCSFB via a noninvasive, low-energy focused shockwave (FSW) pulse (energy flux density 0.03 mJ/mm2) with SonoVue microbubbles (2 × 106 MBs/kg), posing a low risk of injury.ResultsBy opening the BCSFB, the concentrations of certain CNS-impermeable indicators (70 kDa Evans blue and 500 kDa FITC-dextran) and drugs (penicillin G, doxorubicin, and bevacizumab) could be significantly elevated in the CSF around both the brain and the spinal cord. Moreover, glioblastoma model rats treated by doxorubicin with this FSW-induced BCSFB (FSW-BCSFB) opening technique also survived significantly longer than untreated controls.ConclusionThis is the first study to demonstrate and validate a method for noninvasively and selectively opening the BCSFB to enhance drug delivery into CSF circulation. Potential applications may include treatments for neurodegenerative diseases, CNS infections, brain tumors, and leptomeningeal carcinomatosis.
Highlights
The brain is a unique organ in that is highly protected from the periphery by two major barriers, the blood– brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB)
After the blood-cerebrospinal fluid (CSF) barrier (BCSFB) was opened by focused shockwave pulse (FSW), a strong fluorescence signal was observed around the center of the spinal cord in the FSW-UCA treatment group, but a similar signal was not observed in the control group
These results indicate that this FSW-based technique can open the BCSFB and deliver drugs into the CSF circulation
Summary
The brain is a unique organ in that is highly protected from the periphery by two major barriers, the blood– brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). The mechanisms by which the BBB and the BCSFB protect the brain/CSF from pathogens and toxins block drug delivery [1, 2]. High-intensity focused ultrasound (HIFU), a method commonly used to open the BBB, can provide a shorter delivery window, reducing the risk of infection but limiting the area to which drugs can be delivered [4]. The blood-cerebrospinal fluid (CSF) barrier (BCSFB) is critically important to the pathophysiology of the central nervous system (CNS). This barrier prevents the safe transmission of beneficial drugs from the blood to the CSF and the spinal cord and brain, limiting their effectiveness in treating a variety of CNS diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
