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

Zhao, Rongjun; Jiang, Jie; Li, Huiwen; Chen, Min; Liu, Renfa; Sun, Shaodong; De, Ma; Liang, Xiaolong; Wang, Shumin

doi:10.1186/s12974-018-1368-1

Cited by 24 publications

(16 citation statements)

References 25 publications

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“…Establishment of a cerebral I/R model. one hour after the last administration, the focal cerebral I/R rat model was prepared using the middle cerebral artery occlusion (MCAO) method, as previously reported with slight modifications (22). In brief, following weighing, the rats were anesthetized with 1% pentobarbital (50 mg/kg; i.p) and fixed in the supine position on a heated operating table with the body temperature maintained at 37±0.5˚C.…”

Section: Methodsmentioning

confidence: 99%

Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF‑κB signaling pathway

et al. 2020

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Eupatorium perfoliatum L. (E. perfoliatium) has been used traditionally for treating fever, malaria and inflammation-associated diseases. Eupafolin, the extract of E. perfoliatium, was also reported to suppress inflammation. The present study aimed to investigate the protective effects of eupafolin on cerebral ischemia/reperfusion (I/R) injury in rats and its possible underlying mechanisms. Cerebral I/R injury was induced in rats by middle cerebral artery occlusion (MCAO) for 1.5 h, followed by reperfusion. The rats were randomly assigned into six groups: Control, model, 10 mg/kg eupafolin, 20 mg/kg eupafolin, 50 mg/kg eupafolin and 20 mg/kg nimodipine. Eupafolin and nimodipine were intragastrically administrated to the rats 1 week before MCAO induction. Following reperfusion for 24 h, the neurological deficit was scored, and brain samples were harvested for evaluating encephaledema, infarct volume, oxidative stress, apoptosis, inflammation and the expression of TLR4/NF-κB signaling. The results revealed that eupafolin decreased the neurological score, relieved encephaledema and decreased infarct volume. Eupafolin also attenuated oxidative stress, neuronal apoptosis and inflammation, with decreases in lactate dehydrogenase, malondialdehyde, TUNEL-positive cells, Bax and caspase-3, along with TnF-α, il-1β and IL-6, but increases in superoxide dismutase and Bcl-2 levels. Furthermore, eupafolin may decrease the expression of TLR4 downstream proteins and proteins involved in the NF-κB pathway. Treatment with TLR4 agonist-LPS significantly blunted the protective effect of eupafolin on encephaledema and cerebral infarct. Meanwhile, 20 mg/kg eupafolin showed nearly equivalent effects to the positive-control drug nimodipine. In conclusion, eupafolin protected against cerebral I/R injury in rats and the underlying mechanism may be associated with the suppression of apoptosis and inflammation via inhibiting the TLR4/ nF-κB signaling pathway.

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Section: Methodsmentioning

confidence: 99%

Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF‑κB signaling pathway

et al. 2020

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“…Several studies came up with other innovative drug delivery. Briefly, Zhao et al used phosphatidylserine nanoparticles-microbubbles complexes to monitor inflammatory reaction [ 113 ]. The complex successfully and safely opened the BBB and activated the microglia/macrophage in the rat brain.…”

Section: Recent Advances On Sono-sensitive Agents For Ultrasound-amentioning

confidence: 99%

Recent Advances on Ultrasound Contrast Agents for Blood-Brain Barrier Opening with Focused Ultrasound

et al. 2020

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The blood-brain barrier is the primary obstacle to efficient intracerebral drug delivery. Focused ultrasound, in conjunction with microbubbles, is a targeted and non-invasive way to disrupt the blood-brain barrier. Many commercially available ultrasound contrast agents and agents specifically designed for therapeutic purposes have been investigated in ultrasound-mediated blood-brain barrier opening studies. The new generation of sono-sensitive agents, such as liquid-core droplets, can also potentially disrupt the blood-brain barrier after their ultrasound-induced vaporization. In this review, we describe the different compositions of agents used for ultrasound-mediated blood-brain barrier opening in recent studies, and we discuss the challenges of the past five years related to the optimal formulation of agents.

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“…It is difficult to maximize the efficacy of the drug in cardiac aggregation. Combined with UTMD, the cavitation effect and mechanical action produced by the instantaneous blasting of ultrasound microbubbles can cause temporary open pores (Chen et al, 2013;Qian et al, 2018;Zhao et al, 2018) on the endothelial cell membrane and capillaries of the myocardium. The target delivery of FGF1-nlip to the myocardium can realize the rapid release of the target and rapid penetration, thus realizing the myocardial transmission of FGF1 and exerting its biological function.…”

Section: Discussionmentioning

confidence: 99%

Assessment of the Preventive Effect Against Diabetic Cardiomyopathy of FGF1-Loaded Nanoliposomes Combined With Microbubble Cavitation by Ultrasound

Zheng

Shen

et al. 2020

Front. Pharmacol.

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Acidic fibroblast growth factor (FGF1) has great potential in preventing diabetic cardiomyopathy. This study aimed to evaluate the preventive effect of FGF1-loaded nanoliposomes (FGF1-nlip) combined with ultrasound-targeted microbubble destruction (UTMD) on diabetic cardiomyopathy (DCM) using ultrasound examination. Nanoliposomes encapsulating FGF1 were prepared by reverse phase evaporation. DM model rats were established by intraperitoneal injection of streptozotocin (STZ), and different forms of FGF1 (FGF1 solution, FGF1-nlip, and FGF1-nlip+UTMD) were used for a 12-week intervention. According to the transthoracic echocardiography and velocity vector imaging (VVI) indexes, the LVEF, LVFS, and VVI indexes (Vs, Sr, SRr) in the FGF1-nlip+UTMD group were significantly higher than those in the DM model group and other FGF1 intervention groups. From the realtime myocardial contrast echocardiography (RT-MCE) indexes, the FGF1-nlip+UTMD group A and A×b showed significant differences from the DM model group and other FGF1 intervention groups. Cardiac catheter hemodynamic testing, CD31 immunohistochemical staining, and electron microscopy also confirmed the same conclusion. These results confirmed that the abnormalities, including myocardial dysfunction and perfusion impairment, could be suppressed to different extents by the twice weekly FGF1 treatments for 12 consecutive weeks (free FGF1, FGF1-nlip, and FGF1-nlip+UTMD), with the strongest improvements observed in the FGF1-nlip+UTMD group. In conclusion, the VVI and RT-MCE techniques can detect left ventricular systolic function and perfusion changes in DM rats, providing a more effective experimental basis for the early detection and treatment evaluation of DCM, which is of great significance for the prevention of DCM.

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

Cited by 24 publications

References 25 publications

Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF‑κB signaling pathway

Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF‑κB signaling pathway

Recent Advances on Ultrasound Contrast Agents for Blood-Brain Barrier Opening with Focused Ultrasound

Assessment of the Preventive Effect Against Diabetic Cardiomyopathy of FGF1-Loaded Nanoliposomes Combined With Microbubble Cavitation by Ultrasound

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