Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood–brain barrier

Abstract Background and purpose Inflammatory reaction plays a crucial role in cerebral ischemia reperfusion (IR) injury. It has been shown that activated microglia long-term existed in cerebral ischemia and induced second injury. Therefore, we hypothesize that prepared phosphatidylserine (PS)-modifi...

Full description

Bibliographic Details
Main Authors: Ranran Zhao, Jie Jiang, Huiwen Li, Min Chen, Renfa Liu, Sujuan Sun, De Ma, Xiaolong Liang, Shumin Wang
Format: Article
Language:English
Published: BMC 2018-11-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12974-018-1368-1
_version_ 1818154055544864768
author Ranran Zhao
Jie Jiang
Huiwen Li
Min Chen
Renfa Liu
Sujuan Sun
De Ma
Xiaolong Liang
Shumin Wang
author_facet Ranran Zhao
Jie Jiang
Huiwen Li
Min Chen
Renfa Liu
Sujuan Sun
De Ma
Xiaolong Liang
Shumin Wang
author_sort Ranran Zhao
collection DOAJ
description Abstract Background and purpose Inflammatory reaction plays a crucial role in cerebral ischemia reperfusion (IR) injury. It has been shown that activated microglia long-term existed in cerebral ischemia and induced second injury. Therefore, we hypothesize that prepared phosphatidylserine (PS)-modified microbubbles (PS-MBs) combined with ultrasound-targeted microbubble destruction (UTMD) can safely open the blood–brain barrier (BBB) and target activated microglia for inflammatory area in the later stage of ischemia reperfusion. Methods To verify our hypothesis, rat model of IR was established, then the change of activated microglia/macrophage (M/M) and permeability of BBB at 1, 7, 14, and 21 days could be clearly observed post IR. And the activated M/M still can be observed during the whole experiment. Results The Evans blue extravasation of BBB gradually declined from day 1 to day 21. Compared to the control group, microbubbles containing PS were taken up more by activated M/M (approximately twofold) both in vitro and in vivo. Conclusions PS-MBs combined with ultrasound (US) exposure could safely open BBB, and the resulting PS nanoparticles (PS-NPs) could further target activated M/M in the neuroinflammation.
first_indexed 2024-12-11T14:20:26Z
format Article
id doaj.art-3fff26cf146f492992b1720eb81cfdcb
institution Directory Open Access Journal
issn 1742-2094
language English
last_indexed 2024-12-11T14:20:26Z
publishDate 2018-11-01
publisher BMC
record_format Article
series Journal of Neuroinflammation
spelling doaj.art-3fff26cf146f492992b1720eb81cfdcb2022-12-22T01:02:57ZengBMCJournal of Neuroinflammation1742-20942018-11-0115111010.1186/s12974-018-1368-1Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood–brain barrierRanran Zhao0Jie Jiang1Huiwen Li2Min Chen3Renfa Liu4Sujuan Sun5De Ma6Xiaolong Liang7Shumin Wang8Ordos Center HospitalDepartment of Ultrasound, Peking University Third HospitalOrdos Center HospitalDepartment of Biomedical Engineering, College of Engineering, Peking UniversityDepartment of Biomedical Engineering, College of Engineering, Peking UniversityOrdos Center HospitalOrdos Center HospitalDepartment of Ultrasound, Peking University Third HospitalOrdos Center HospitalAbstract Background and purpose Inflammatory reaction plays a crucial role in cerebral ischemia reperfusion (IR) injury. It has been shown that activated microglia long-term existed in cerebral ischemia and induced second injury. Therefore, we hypothesize that prepared phosphatidylserine (PS)-modified microbubbles (PS-MBs) combined with ultrasound-targeted microbubble destruction (UTMD) can safely open the blood–brain barrier (BBB) and target activated microglia for inflammatory area in the later stage of ischemia reperfusion. Methods To verify our hypothesis, rat model of IR was established, then the change of activated microglia/macrophage (M/M) and permeability of BBB at 1, 7, 14, and 21 days could be clearly observed post IR. And the activated M/M still can be observed during the whole experiment. Results The Evans blue extravasation of BBB gradually declined from day 1 to day 21. Compared to the control group, microbubbles containing PS were taken up more by activated M/M (approximately twofold) both in vitro and in vivo. Conclusions PS-MBs combined with ultrasound (US) exposure could safely open BBB, and the resulting PS nanoparticles (PS-NPs) could further target activated M/M in the neuroinflammation.http://link.springer.com/article/10.1186/s12974-018-1368-1IschemiaBlood–brain barrierUltrasound-targeted microbubble destructionMicrobubblesPhosphatidylserine
spellingShingle Ranran Zhao
Jie Jiang
Huiwen Li
Min Chen
Renfa Liu
Sujuan Sun
De Ma
Xiaolong Liang
Shumin Wang
Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood–brain barrier
Journal of Neuroinflammation
Ischemia
Blood–brain barrier
Ultrasound-targeted microbubble destruction
Microbubbles
Phosphatidylserine
title Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood–brain barrier
title_full Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood–brain barrier
title_fullStr Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood–brain barrier
title_full_unstemmed Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood–brain barrier
title_short Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood–brain barrier
title_sort phosphatidylserine microbubble targeting activated microglia macrophage in inflammation combined with ultrasound for breaking through the blood brain barrier
topic Ischemia
Blood–brain barrier
Ultrasound-targeted microbubble destruction
Microbubbles
Phosphatidylserine
url http://link.springer.com/article/10.1186/s12974-018-1368-1
work_keys_str_mv AT ranranzhao phosphatidylserinemicrobubbletargetingactivatedmicrogliamacrophageininflammationcombinedwithultrasoundforbreakingthroughthebloodbrainbarrier
AT jiejiang phosphatidylserinemicrobubbletargetingactivatedmicrogliamacrophageininflammationcombinedwithultrasoundforbreakingthroughthebloodbrainbarrier
AT huiwenli phosphatidylserinemicrobubbletargetingactivatedmicrogliamacrophageininflammationcombinedwithultrasoundforbreakingthroughthebloodbrainbarrier
AT minchen phosphatidylserinemicrobubbletargetingactivatedmicrogliamacrophageininflammationcombinedwithultrasoundforbreakingthroughthebloodbrainbarrier
AT renfaliu phosphatidylserinemicrobubbletargetingactivatedmicrogliamacrophageininflammationcombinedwithultrasoundforbreakingthroughthebloodbrainbarrier
AT sujuansun phosphatidylserinemicrobubbletargetingactivatedmicrogliamacrophageininflammationcombinedwithultrasoundforbreakingthroughthebloodbrainbarrier
AT dema phosphatidylserinemicrobubbletargetingactivatedmicrogliamacrophageininflammationcombinedwithultrasoundforbreakingthroughthebloodbrainbarrier
AT xiaolongliang phosphatidylserinemicrobubbletargetingactivatedmicrogliamacrophageininflammationcombinedwithultrasoundforbreakingthroughthebloodbrainbarrier
AT shuminwang phosphatidylserinemicrobubbletargetingactivatedmicrogliamacrophageininflammationcombinedwithultrasoundforbreakingthroughthebloodbrainbarrier