Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse
Abstract Background The 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...
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Fluids and Barriers of the CNS |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12987-021-00303-x |
| _version_ | 1818940617451896832 |
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| author | Yi Kung Kuan-Yu Chen Wei-Hao Liao Yi-Hua Hsu Chueh-Hung Wu Ming-Yen Hsiao Abel P.-H. Huang Wen-Shiang Chen |
| author_facet | Yi Kung Kuan-Yu Chen Wei-Hao Liao Yi-Hua Hsu Chueh-Hung Wu Ming-Yen Hsiao Abel P.-H. Huang Wen-Shiang Chen |
| author_sort | Yi Kung |
| collection | DOAJ |
| description | Abstract Background The 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. Methods This 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. Results By 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. Conclusion This 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. |
| first_indexed | 2024-12-20T06:42:29Z |
| format | Article |
| id | doaj.art-11d55569809b4381a861063dba266c3b |
| institution | Directory Open Access Journal |
| issn | 2045-8118 |
| language | English |
| last_indexed | 2024-12-20T06:42:29Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj.art-11d55569809b4381a861063dba266c3b2022-12-21T19:49:49ZengBMCFluids and Barriers of the CNS2045-81182022-01-0119111310.1186/s12987-021-00303-xFacilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulseYi Kung0Kuan-Yu Chen1Wei-Hao Liao2Yi-Hua Hsu3Chueh-Hung Wu4Ming-Yen Hsiao5Abel P.-H. Huang6Wen-Shiang Chen7Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of MedicineDivision of Pulmonology, Department of Internal Medicine, National Taiwan University Hospital and College of MedicineDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of MedicineDepartment of Surgery, National Taiwan University HospitalDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of MedicineDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of MedicineDepartment of Surgery, National Taiwan University HospitalDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of MedicineAbstract Background The 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. Methods This 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. Results By 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. Conclusion This 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.https://doi.org/10.1186/s12987-021-00303-xLow-energy extracorporeal focused shockwave pulseBlood–brain barrierBlood-cerebrospinal fluid barrierCentral nervous systemGlioblastoma multiformeLeptomeningeal carcinomatosis |
| spellingShingle | Yi Kung Kuan-Yu Chen Wei-Hao Liao Yi-Hua Hsu Chueh-Hung Wu Ming-Yen Hsiao Abel P.-H. Huang Wen-Shiang Chen Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse Fluids and Barriers of the CNS Low-energy extracorporeal focused shockwave pulse Blood–brain barrier Blood-cerebrospinal fluid barrier Central nervous system Glioblastoma multiforme Leptomeningeal carcinomatosis |
| title | Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse |
| title_full | Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse |
| title_fullStr | Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse |
| title_full_unstemmed | Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse |
| title_short | Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse |
| title_sort | facilitating drug delivery in the central nervous system by opening the blood cerebrospinal fluid barrier with a single low energy shockwave pulse |
| topic | Low-energy extracorporeal focused shockwave pulse Blood–brain barrier Blood-cerebrospinal fluid barrier Central nervous system Glioblastoma multiforme Leptomeningeal carcinomatosis |
| url | https://doi.org/10.1186/s12987-021-00303-x |
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