scholarly journals PTD4 Peptide Increases Neural Viability in an In Vitro Model of Acute Ischemic Stroke

2021 ◽  
Vol 22 (11) ◽  
pp. 6086
Author(s):  
Jarosław Mazuryk ◽  
Izabela Puchalska ◽  
Kamil Koziński ◽  
Magdalena J. Ślusarz ◽  
Jarosław Ruczyński ◽  
...  

Ischemic stroke is a disturbance in cerebral blood flow caused by brain tissue ischemia and hypoxia. We optimized a multifactorial in vitro model of acute ischemic stroke using rat primary neural cultures. This model was exploited to investigate the pro-viable activity of cell-penetrating peptides: arginine-rich Tat(49–57)-NH2 (R49KKRRQRRR57-amide) and its less basic analogue, PTD4 (Y47ARAAARQARA57-amide). Our model included glucose deprivation, oxidative stress, lactic acidosis, and excitotoxicity. Neurotoxicity of these peptides was excluded below a concentration of 50 μm, and PTD4-induced pro-survival was more pronounced. Circular dichroism spectroscopy and molecular dynamics (MD) calculations proved potential contribution of the peptide conformational properties to neuroprotection: in MD, Tat(49–57)-NH2 adopted a random coil and polyproline type II helical structure, whereas PTD4 adopted a helical structure. In an aqueous environment, the peptides mostly adopted a random coil conformation (PTD4) or a polyproline type II helical (Tat(49–57)-NH2) structure. In 30% TFE, PTD4 showed a tendency to adopt a helical structure. Overall, the pro-viable activity of PTD4 was not correlated with the arginine content but rather with the peptide’s ability to adopt a helical structure in the membrane-mimicking environment, which enhances its cell membrane permeability. PTD4 may act as a leader sequence in novel drugs for the treatment of acute ischemic stroke.

2020 ◽  
Vol 12 (10) ◽  
pp. 1002-1007
Author(s):  
Sarah Johnson ◽  
Ray McCarthy ◽  
Brian Fahy ◽  
Oana Madalina Mereuta ◽  
Seán Fitzgerald ◽  
...  

​BackgroundCalcified cerebral emboli (CCEs) are a rare cause of acute ischemic stroke (AIS) and are frequently associated with poor outcomes. The presence of dense calcified material enables reliable identification of CCEs using non-contrast CT. However, recanalization rates with the available mechanical thrombectomy (MT) devices remain low.ObjectiveTo recreate a large vessel occlusion involving a CCE using an in vitro silicone model of the intracranial vessels and to demonstrate the feasability of this model to test different endovascular strategies to recanalize an occlusion of the M1 segment of the middle cerebral artery (MCA).​MethodsAn in vitro model was developed to evaluate different endovascular treatment approaches using contemporary devices in the M1 segment of the MCA. The in vitro model consisted of a CCE analog placed in a silicone neurovascular model. Development of an appropriate CCE analog was based on characterization of human calcified tissues that represent likely sources of CCEs. Feasibility of the model was demonstrated in a small number of MT devices using four common procedural techniques.​ResultsCCE analogs were developed with similar mechanical behavior to that of ex vivo calcified material. The in vitro model was evaluated with various MT techniques and devices to show feasibility of the model. In this limited evaluation, the most successful retrieval approach was performed with a stent retriever combined with local aspiration through a distal access catheter, and importantly, with flow arrest and dual aspiration using a balloon guide catheter.​ConclusionCharacterization of calcified tissues, which are likely sources of CCEs, has shown that CCEs are considerably stiffer than thrombus. This highlights the need for a different in vitro AIS model for CCEs than those used for thromboemboli. Consequentially, an in vitro AIS model representative of a CCE occlusion in the M1 segment of the MCA has been developed.


1984 ◽  
Vol 10 (3) ◽  
pp. 375-378 ◽  
Author(s):  
Donald L. Shapiro ◽  
Jacob N. Finkelstein ◽  
Philip Rubin ◽  
David P. Penney ◽  
Dietmar W. Siemann

Lab on a Chip ◽  
2019 ◽  
Vol 19 (2) ◽  
pp. 241-253 ◽  
Author(s):  
Yunxiao Liu ◽  
Patthara Kongsuphol ◽  
Su Yin Chiam ◽  
Qing Xin Zhang ◽  
Sajay Bhuvanendran Nair Gourikutty ◽  
...  

Infiltration of immune cells into adipose tissue is associated with chronic low-grade inflammation in obese individuals.


Author(s):  
Li Yang ◽  
Kaushik K. Shah ◽  
Thomas J. Abbruscato

2021 ◽  
pp. 159101992110150
Author(s):  
Naoki Kaneko ◽  
Mahsa Ghovvati ◽  
Yutaro Komuro ◽  
Lea Guo ◽  
Kasra Khatibi ◽  
...  

Objective Fragile soft clots and stiff clots remain challenging in the treatment of acute ischemic stroke. This study aims to investigate the impact of clot stiffness on the efficacy of thrombectomy devices and a new aspiration catheter with a hydro-separator. Methods The Neurostar aspiration catheter has a novel hydro-separator technology that macerates clots by a stream of saline inside the catheter. The Neurostar catheter and two commercially available devices, the SOFIA aspiration catheter and Solitaire stent retriever, were tested in this study. We evaluated the efficacy of each device on clots with various stiffness in a simple in vitro model. We also assessed single-pass recanalization performance in challenging situations with large erythrocyte-rich clots and fibrin-rich clots in a realistic vascular model. Results We observed an inverse association between the clot stiffness and recanalization rates. The aspiration catheter, SOFIA ingested soft clots but not moderately stiff clots. When removing soft clots with the stent retriever, fragmentation was observed, although relatively stiff clots were well-integrated and removed. The Neurostar ingested soft clots similar to the aspiration catheter, and also aspirated stiff clots by continuous suction with hydro-separator. In the experiments with challenging clots, the Neurostar led to significantly higher recanalization rates than the stent retriever and aspiration catheter. Conclusions The stiffness of the clots affected the efficacy of endovascular thrombectomy based on the type of device. The Neurostar catheter with hydro-separator resulted in better success rates than a commercially available aspiration catheter and stent retriever in this experimental model.


2014 ◽  
Vol 10 (8) ◽  
pp. 873-881 ◽  
Author(s):  
Sui-yi Xu ◽  
Ya-fang Hu ◽  
Wei-pin Li ◽  
Yong-ming Wu ◽  
Zhong Ji ◽  
...  

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