Blood-cerebrospinal fluid barrier opening by modified single pulse transcranial focused shockwave
AbstractTranscranial focused shockwave (FSW) is a novel noninvasive brain stimulation that can open blood-brain barriers (BBB) and blood-cerebrospinal fluid barriers (BCSFB) with a single low-energy (energy flux density 0.03 mJ/mm2) pulse and low-dose microbubbles (2 × 106/kg). Similar to focused ul...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2022.2157068 |
| _version_ | 1827317431268278272 |
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| author | Yi Kung Chueh-Hung Wu Meng-Ting Lin Wei-Hao Liao Wen-Shiang Chen Ming-Yen Hsiao |
| author_facet | Yi Kung Chueh-Hung Wu Meng-Ting Lin Wei-Hao Liao Wen-Shiang Chen Ming-Yen Hsiao |
| author_sort | Yi Kung |
| collection | DOAJ |
| description | AbstractTranscranial focused shockwave (FSW) is a novel noninvasive brain stimulation that can open blood-brain barriers (BBB) and blood-cerebrospinal fluid barriers (BCSFB) with a single low-energy (energy flux density 0.03 mJ/mm2) pulse and low-dose microbubbles (2 × 106/kg). Similar to focused ultrasound, FSW deliver highly precise stimulation of discrete brain regions with adjustable focal lengths that essentially covers the whole brain. By opening the BCSFB, it allows for rapid widespread drug delivery to the whole brain by cerebrospinal fluid (CSF) circulation. Although no definite adverse effect or permeant injury was noted in our previous study, microscopic hemorrhage was infrequently observed. Safety concerns remain the major obstacle to further application of FSW in brain. To enhance its applicability, a modified single pulse FSW technique was established that present 100% opening rate but much less risk of adverse effect than previous methods. By moving the targeting area 2.5 mm more superficially on the left lateral ventricle as compared with the previous methods, the microscopic hemorrhage rate was reduced to zero. We systemically examine the safety profiles of the modified FSW-BCSFB opening regarding abnormal behavior and brain injury or hemorrhage 72 hr after 0, 1, and 10 pulses of FSW-treatment. Animal behavior, physiological monitor, and brain MRI were examined and recorded. Brain section histology was examined for hemorrhage, apoptosis, inflammation, oxidative stress related immunohistochemistry and biomarkers. The single pulse FSW group demonstrated no mortality or gross/microscopic hemorrhage (N = 30), and no observable changes in all examined outcomes, while 10 pulses of FSW was found to be associated with microscopic and temporary RBC extravasation (N = 6/30), and abnormal immunohistochemistry biomarkers which showed a trend of recovery at 72 hrs. The results suggest that single pulse low-energy FSW-BCSFB opening is effective, safe and poses minimal risk of injury to brain tissue (Sprague Dawley, SD rats). |
| first_indexed | 2024-03-08T23:30:28Z |
| format | Article |
| id | doaj.art-20daa985de8d4773b92e76d624742599 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-04-24T23:33:11Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-20daa985de8d4773b92e76d6247425992024-03-15T14:22:18ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642023-12-013019710710.1080/10717544.2022.2157068Blood-cerebrospinal fluid barrier opening by modified single pulse transcranial focused shockwaveYi Kung0Chueh-Hung Wu1Meng-Ting Lin2Wei-Hao Liao3Wen-Shiang Chen4Ming-Yen Hsiao5Department of Biomechatronic Engineering, National Chiayi University, Chiayi City, TaiwanDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of Medicine, Taipei City, TaiwanDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of Medicine, Taipei City, TaiwanDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of Medicine, Taipei City, TaiwanDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of Medicine, Taipei City, TaiwanDepartment of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of Medicine, Taipei City, TaiwanAbstractTranscranial focused shockwave (FSW) is a novel noninvasive brain stimulation that can open blood-brain barriers (BBB) and blood-cerebrospinal fluid barriers (BCSFB) with a single low-energy (energy flux density 0.03 mJ/mm2) pulse and low-dose microbubbles (2 × 106/kg). Similar to focused ultrasound, FSW deliver highly precise stimulation of discrete brain regions with adjustable focal lengths that essentially covers the whole brain. By opening the BCSFB, it allows for rapid widespread drug delivery to the whole brain by cerebrospinal fluid (CSF) circulation. Although no definite adverse effect or permeant injury was noted in our previous study, microscopic hemorrhage was infrequently observed. Safety concerns remain the major obstacle to further application of FSW in brain. To enhance its applicability, a modified single pulse FSW technique was established that present 100% opening rate but much less risk of adverse effect than previous methods. By moving the targeting area 2.5 mm more superficially on the left lateral ventricle as compared with the previous methods, the microscopic hemorrhage rate was reduced to zero. We systemically examine the safety profiles of the modified FSW-BCSFB opening regarding abnormal behavior and brain injury or hemorrhage 72 hr after 0, 1, and 10 pulses of FSW-treatment. Animal behavior, physiological monitor, and brain MRI were examined and recorded. Brain section histology was examined for hemorrhage, apoptosis, inflammation, oxidative stress related immunohistochemistry and biomarkers. The single pulse FSW group demonstrated no mortality or gross/microscopic hemorrhage (N = 30), and no observable changes in all examined outcomes, while 10 pulses of FSW was found to be associated with microscopic and temporary RBC extravasation (N = 6/30), and abnormal immunohistochemistry biomarkers which showed a trend of recovery at 72 hrs. The results suggest that single pulse low-energy FSW-BCSFB opening is effective, safe and poses minimal risk of injury to brain tissue (Sprague Dawley, SD rats).https://www.tandfonline.com/doi/10.1080/10717544.2022.2157068Safetyshockwaveblood-cerebrospinal fluid barrierCSF circulationbrain |
| spellingShingle | Yi Kung Chueh-Hung Wu Meng-Ting Lin Wei-Hao Liao Wen-Shiang Chen Ming-Yen Hsiao Blood-cerebrospinal fluid barrier opening by modified single pulse transcranial focused shockwave Drug Delivery Safety shockwave blood-cerebrospinal fluid barrier CSF circulation brain |
| title | Blood-cerebrospinal fluid barrier opening by modified single pulse transcranial focused shockwave |
| title_full | Blood-cerebrospinal fluid barrier opening by modified single pulse transcranial focused shockwave |
| title_fullStr | Blood-cerebrospinal fluid barrier opening by modified single pulse transcranial focused shockwave |
| title_full_unstemmed | Blood-cerebrospinal fluid barrier opening by modified single pulse transcranial focused shockwave |
| title_short | Blood-cerebrospinal fluid barrier opening by modified single pulse transcranial focused shockwave |
| title_sort | blood cerebrospinal fluid barrier opening by modified single pulse transcranial focused shockwave |
| topic | Safety shockwave blood-cerebrospinal fluid barrier CSF circulation brain |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2022.2157068 |
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