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1. Histological composition of retrieved emboli in acute ischemic stroke is independent of pre-thrombectomy alteplase use

Author

Brinjikji, Waleed, Abbasi, Mehdi, Mereuta, Oana Madalina, Fitzgerald, Seán, Larco, Jorge Arturo, Dai, Daying, Kadirvel, Ramanathan, Nogueira, Raul G., Kvamme, Peter, Layton, Kennith F., Delgado, Josser E., Hanel, Ricardo A., Pereira, Vitor M., Almekhlafi, Mohammed A., Yoo, Albert J., Jahromi, Babak S., Gounis, Matthew J., Patel, Biraj M., Savastano, Luis E., Cloft, Harry J., Haussen, Diogo C., Al-Bayati, Alhamza, Mohammaden, Mahmoud, Pisani, Leonardo, Rodrigues, Gabriel, Thacker, Ike C., Kayan, Yasha, Copelan, Alexander Z., Aghaebrahim, Amin, Sauvageau, Eric, Demchuk, Andrew M., Bhuva, Parita, Soomro, Jazba, Nazari, Pouya, Cantrell, Donald Robert, Puri, Ajit S., Doyle, Karen M., Entwistle, John, and Kallmes, David F.

Published
2022
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2. Homocysteine concentration in coronary artery disease and severity of coronary lesions.

Author

Luo, Zhi, Tang, Kai, Huang, Gang, Wang, Xiao, Zhou, Shiheng, Dai, Daying, Yang, Hanxuan, and Jiang, Wencai

Subjects
CORONARY artery disease, HOMOCYSTEINE, LDL cholesterol, CHINESE people, CORONARY artery stenosis
Abstract

Our previous study reckons that the impact of the rs1801133 variant of 5,10‐methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD‐free individuals were enrolled in this case–control study. The rs1801133 variant was genotyped by PCR‐RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD‐free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low‐density lipoprotein cholesterol (LDL‐C), and high‐sensitivity C‐reactive protein (hs‐CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision‐recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs‐CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions. [ABSTRACT FROM AUTHOR]

Published
2024
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4. WEB shape modifications: angiography--histopathology correlations in rabbits.

Author

Janot, Kevin, Boulouis, Grégoire, Forestier, Géraud, Bala, Fouzi, Cortese, Jonathan, Szatmáry, Zoltán, Bardet, Sylvia M., Baudouin, Maxime, Perrin, Marie-Laure, Mounier, Jérémy, Couquet, Claude, Yardin, Catherine, Segonds, Guillaume, Dubois, Nicolas, Martinez, Alexandra, Lesage, Pierre-Louis, Ding, Yong-Hong, Kadirvel, Ramanathan, Dai, Daying, and Mounayer, Charbel

Subjects
ANEURYSM surgery, STATISTICAL correlation, PATHOLOGY, RESEARCH funding, THERAPEUTIC embolization, COMPUTED tomography, CORONARY occlusion, FISHER exact test, ANGIOGRAPHY, ENDOVASCULAR surgery, QUANTITATIVE research, DESCRIPTIVE statistics, MANN Whitney U Test, CHI-squared test, LONGITUDINAL method, ANIMAL experimentation, RESEARCH, COMPARATIVE studies, HISTOLOGY, RABBITS
Abstract

Background WEB Shape Modification (WSM) over time is frequent after aneurysm treatment. In this study, we explored the relationship between histopathological changes and angiographic evolution over time in experimental aneurysms in rabbits treated with the Woven EndoBridge (WEB) procedure. Methods Quantitative WSM was assessed using flat-panel computed tomography (FPCT) during follow-up by calculating height and width ratio (HR, WR), defined as the ratio between either measurement at an index time point and the measurement immediately after WEB implantation. The index time point varied from 1 day to 6 months. HR and WR were evaluated with angiographic and histopathological assessments of aneurysm healing. Results Final HR of devices varied from 0.30 to 1.02 and final WR varied from 0.62 to 1.59. Altogether, at least 5% of HR and WR variations were observed in 37/40 (92.5%) and 28/40 (70%) WEB devices, respectively, at the time of final assessment. There was no significant correlation between complete or incomplete occlusion groups and HR or WR (p=0.15 and p=0.43). Histopathological analysis revealed a significant association between WR and aneurysm healing and fibrosis 1 month following aneurysm treatment (both p<0.05). Conclusion Using longitudinal FPCT assessment, we observed that WSM affects both the height and width of the WEB device. No significant association was found between WSM and aneurysm occlusion status. Although presumably a multifactorial phenomenon, the histopathological analysis highlighted a significant association between width variations, aneurysm healing and fibrosis in the first month following aneurysm treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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5. WEB shape modifications: angiography–histopathology correlations in rabbits

Author

Janot, Kevin, primary, Boulouis, Grégoire, additional, Forestier, Géraud, additional, Bala, Fouzi, additional, Cortese, Jonathan, additional, Szatmáry, Zoltán, additional, Bardet, Sylvia M., additional, Baudouin, Maxime, additional, Perrin, Marie-Laure, additional, Mounier, Jérémy, additional, Couquet, Claude, additional, Yardin, Catherine, additional, Segonds, Guillaume, additional, Dubois, Nicolas, additional, Martinez, Alexandra, additional, Lesage, Pierre-Louis, additional, Ding, Yong-Hong, additional, Kadirvel, Ramanathan, additional, Dai, Daying, additional, Mounayer, Charbel, additional, Terro, Faraj, additional, and Rouchaud, Aymeric, additional

Published
2023
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7. Platelet-Rich Emboli in Cerebral Large Vessel Occlusion Are Associated With a Large Artery Atherosclerosis Source

Author

Fitzgerald, Seán, Dai, Daying, Wang, Shunli, Douglas, Andrew, Kadirvel, Ramanathan, Layton, Kennith F., Thacker, Ike C., Gounis, Matthew J., Chueh, Ju-Yu, Puri, Ajit S., Almekhlafi, Mohammed, Demchuk, Andrew M., Hanel, Ricardo A., Sauvageau, Eric, Aghaebrahim, Amin, Yoo, Albert J., Kvamme, Peter, M. Pereira, Vitor, Kayan, Yasha, Delgado Almandoz, Josser E., Nogueira, Raul G., Rabinstein, Alejandro A., Kallmes, David F., Doyle, Karen M., and Brinjikji, Waleed

Published
2019
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9. Correlation of von Willebrand factor and platelets with acute ischemic stroke etiology and revascularization outcome: an immunohistochemical study

Author

Mereuta, Oana Madalina, primary, Abbasi, Mehdi, additional, Arturo Larco, Jorge L, additional, Dai, Daying, additional, Liu, Yang, additional, Arul, Santhosh, additional, Kadirvel, Ramanathan, additional, Hanel, Ricardo A, additional, Yoo, Albert J, additional, Almekhlafi, Mohammed A, additional, Layton, Kennith F, additional, Delgado Almandoz, Josser E, additional, Kvamme, Peter, additional, Mendes Pereira, Vitor, additional, Jahromi, Babak S, additional, Nogueira, Raul G, additional, Gounis, Matthew J, additional, Patel, Biraj, additional, Aghaebrahim, Amin, additional, Sauvageau, Eric, additional, Bhuva, Parita, additional, Soomro, Jazba, additional, Demchuk, Andrew M, additional, Thacker, Ike C, additional, Kayan, Yasha, additional, Copelan, Alexander, additional, Nazari, Pouya, additional, Cantrell, Donald Robert, additional, Haussen, Diogo C, additional, Al-Bayati, Alhamza R, additional, Mohammaden, Mahmoud, additional, Pisani, Leonardo, additional, Rodrigues, Gabriel Martins, additional, Puri, Ajit S, additional, Entwistle, John, additional, Meves, Alexander, additional, Savastano, Luis, additional, Cloft, Harry J, additional, Nimjee, Shahid M, additional, McBane II, Robert D, additional, Kallmes, David F, additional, and Brinjikji, Waleed, additional

Published
2022
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13. Neurologic Effects of Gadolinium Retention in the Brain after Gadolinium-based Contrast Agent Administration

Author

Ayers-Ringler, Jennifer, primary, McDonald, Jennifer S., additional, Connors, Margaret A., additional, Fisher, Cody R., additional, Han, Susie, additional, Jakaitis, Daniel R., additional, Scherer, Bradley, additional, Tutor, Gabriel, additional, Wininger, Katheryn M., additional, Dai, Daying, additional, Choi, Doo-Sup, additional, Salisbury, Jeffrey L., additional, Jannetto, Paul J., additional, Bornhorst, Joshua A., additional, Kadirvel, Ram, additional, Kallmes, David F., additional, and McDonald, Robert J., additional

Published
2022
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19. Quantification of clot spatial heterogeneity and its impact on thrombectomy

Author

Liu, Yang, primary, Brinjikji, Waleed, additional, Abbasi, Mehdi, additional, Dai, Daying, additional, Arturo Larco, Jorge L, additional, Madhani, Sarosh Irfan, additional, Shahid, Adnan H, additional, Mereuta, Oana Madalina, additional, Nogueira, Raul G, additional, Kvamme, Peter, additional, Layton, Kennith F, additional, Delgado Almandoz, Josser E, additional, Hanel, Ricardo A, additional, Mendes Pereira, Vitor, additional, Almekhlafi, Mohammed A, additional, Yoo, Albert J, additional, Jahromi, Babak S, additional, Gounis, Matthew J, additional, Patel, Biraj, additional, Fitzgerald, Seán, additional, Doyle, Karen, additional, Haussen, Diogo C, additional, Al-Bayati, Alhamza R, additional, Mohammaden, Mahmoud, additional, Pisani, Leonardo, additional, Rodrigues, Gabriel Martins, additional, Thacker, Ike C, additional, Kayan, Yasha, additional, Copelan, Alexander, additional, Aghaebrahim, Amin, additional, Sauvageau, Eric, additional, Demchuk, Andrew M, additional, Bhuva, Parita, additional, Soomro, Jazba, additional, Nazari, Pouya, additional, Cantrell, Donald Robert, additional, Puri, Ajit S, additional, Entwistle, John, additional, Kadirvel, Ramanathan, additional, Cloft, Harry J, additional, Kallmes, David F, additional, and Savastano, Luis, additional

Published
2021
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23. Correlation of Neutrophil to Lymphocyte Ratio with Expression of Neutrophil Extracellular Traps Within Stroke Emboli.

Author

Larco, Jorge Arturo, Abbasi, Mehdi, Madhani, Sarosh Irfan, Mereuta, Madalina Oana, Liu, Yang, Dai, Daying, Kadirvel, Ramanathan, Savastano, Luis, Kallmes, David F., and Brinjikji, Waleed

Subjects
NEUTROPHIL lymphocyte ratio, ISCHEMIC stroke, STROKE patients, LEUCOCYTES, ERYTHROCYTES
Abstract

Background & Purpose: It has been hypothesized that circulating neutrophils have a direct correlation with the composition of emboli in acute ischemic stroke (AIS). The aim of this study is to evaluate the association between neutrophil-lymphocyte ratio (NLR) in peripheral blood and the expression of neutrophil extracellular traps (NETs) within stroke emboli. Methods: Consecutive patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) that underwent mechanical thrombectomy (MT) were included. Patients were divided into two groups based on NLR median value. Retrieved thrombi were histologically analyzed using Martius Scarlett Blue (MSB) for main thrombus components including red blood cells (RBCs), white blood cells (WBCs), fibrin and platelet. Immunohistochemistry staining for von Willebrand Factor (vWF) and anti-citrullinated H3 (H3Cit; NETs marker) was also performed. Results: Samples from a total of 84 patients were included. The average percentage of RBCs, WBCs, fibrin, platelet, H3Cit, and vWF components in thrombi were 45.1%, 3.5%, 21.8%, 29.6%, 19.7% and 14.8% respectively. When stratifying by NLR group [low (≤3.94) versus high (>3.95)], high NLR group had significantly more WBCs (4.5%), fibrin (24.2%), H3Cit (22.7%) and vWF (17.1%) thrombus fractions compared to low NLR group. Additionally, RBC content (38.8%) was lower in the high NLR group. Conclusions: NLR is correlated with the amounts of WBCs, fibrin, NETs and vWF within the thrombi retrieved from AIS patients due to LVO. [ABSTRACT FROM AUTHOR]

Published
2022
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27. Correlation of von Willebrand factor and platelets with acute ischemic stroke etiology and revascularization outcome: an immunohistochemical study

Author

Mereuta, Oana Madalina, Abbasi, Mehdi, Arturo Larco, Jorge L, Dai, Daying, Liu, Yang, Arul, Santhosh, Kadirvel, Ramanathan, Hanel, Ricardo A, Yoo, Albert J, Almekhlafi, Mohammed A, Layton, Kennith F, Delgado Almandoz, Josser E, Kvamme, Peter, Mendes Pereira, Vitor, Jahromi, Babak S, Nogueira, Raul G, Gounis, Matthew J, Patel, Biraj, Aghaebrahim, Amin, Sauvageau, Eric, Bhuva, Parita, Soomro, Jazba, Demchuk, Andrew M, Thacker, Ike C, Kayan, Yasha, Copelan, Alexander, Nazari, Pouya, Cantrell, Donald Robert, Haussen, Diogo C, Al-Bayati, Alhamza R, Mohammaden, Mahmoud, Pisani, Leonardo, Rodrigues, Gabriel Martins, Puri, Ajit S, Entwistle, John, Meves, Alexander, Savastano, Luis, Cloft, Harry J, Nimjee, Shahid M, McBane, Robert D, Kallmes, David F, and Brinjikji, Waleed

Abstract

BackgroundPlatelets and von Willebrand factor (vWF) are key components of acute ischemic stroke (AIS) emboli. We aimed to investigate the CD42b (platelets)/vWF expression, its association with stroke etiology and the impact these components may have on the clinical/procedural parameters.MethodsCD42b/vWF immunostaining was performed on 288 emboli collected as part of the multicenter STRIP Registry. CD42b/VWF expression and distribution were evaluated. Student’s t-test and χ2test were performed as appropriate.ResultsThe mean CD42b and VWF content in clots was 44.3% and 21.9%, respectively. There was a positive correlation between platelets and vWF (r=0.64, p<0.001**). We found a significantly higher vWF level in the other determined etiology (p=0.016*) and cryptogenic (p=0.049*) groups compared with cardioembolic etiology. No significant difference in CD42b content was found across the etiology subtypes. CD42b/vWF patterns were significantly associated with stroke etiology (p=0.006*). The peripheral pattern was predominant in atherosclerotic clots (36.4%) while the clustering (patchy) pattern was significantly associated with cardioembolic and cryptogenic origin (66.7% and 49.8%, respectively). The clots corresponding to other determined etiology showed mainly a diffuse pattern (28.1%). Two types of platelets were distinguished within the CD42b-positive clusters in all emboli: vWF-positive platelets were observed at the center, surrounded by vWF-negative platelets. Thrombolysis correlated with a high platelet content (p=0.03*). vWF-poor and peripheral CD42b/vWF pattern correlated with first pass effect (p=0.03* and p=0.04*, respectively).ConclusionsThe vWF level and CD42b/vWF distribution pattern in emboli were correlated with AIS etiology and revascularization outcome. Platelet content was associated with response to thrombolysis.

Published
2023
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28. An in vitro model for Extracellular DNA Traps (ETs)-rich Human Thrombus Analogs

Author

Liu, Yang, Dai, Daying, Abbasi, Mehdi, Mereuta, Oana Madalina, Gamb, Scott I, Kadirvel, Ramanathan, Kallmes, David F, and Brinjikji, Waleed

Abstract

BackgroundExtracellular DNA traps (ETs) have important implications in both thrombosis and thrombolysis. Thus, developing benchtop thrombus analogs that recapitulate clinical ETs is potentially of great value for preclinical development and testing of thrombolytic agents and thrombectomy devices. In this study, we aimed to develop ETs-rich thrombus analogs for preclinical testing.MethodsRed blood cell (RBC)-rich, fibrin-rich, and platelet-rich thrombus analogs were created using human whole blood, platelet-poor plasma, and platelet-rich plasma obtained from the blood bank following institutional approval. Peripheral blood mononuclear cells (9.9×106 cells/mL) isolated from human whole blood and lipopolysaccharide (1 µg/mL) were added to induce ETs. Histochemical, immunohistochemistry and immunofluorescence were used to identify thrombus components and ETs. Scanning electronic microscopy was used to investigate the ultrastructure of the thrombus analogs. The thrombus compositions, morphologic features of ETs and citrullinated histone H3 (H3Cit) expression were compared with those of thrombi retrieved from patients by thrombectomy.ResultsETs-rich thrombus analogs were more compacted th-an the ETs-poor thrombus analogs. ETs were identified in both ETs-rich thrombus analogs and patient thrombi showing morphologic features including nuclear lobulation, nuclear swelling, diffused chromatin within cytoplasm, DNA/chromatin extending intracellularly and extracellularly, and extracellular chromatin patches and bundles. In the ETs-poor thrombus analogs, ETs were not observed and H3Cit expression was absent to minimal. The compositions and H3Cit expression in the ETs-rich thrombus analogs fell in the range of patient thrombi.ConclusionsETs-rich thrombus analogs can be consistently created in vitro and may benefit the preclinical development and testing of new thrombolytic agents and thrombectomy devices.

Published
2023
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31. Histological evaluation of acute ischemic stroke thrombi may indicate the occurrence of vessel wall injury during mechanical thrombectomy

Author

Mereuta, Oana Madalina, primary, Abbasi, Mehdi, additional, Fitzgerald, Seán, additional, Dai, Daying, additional, Kadirvel, Ram, additional, Hanel, Ricardo A, additional, Yoo, Albert J, additional, Almekhlafi, Mohammed A, additional, Layton, Kennith F, additional, Delgado Almandoz, Josser E, additional, Kvamme, Peter, additional, Mendes Pereira, Vitor, additional, Jahromi, Babak S, additional, Nogueira, Raul G, additional, Gounis, Matthew J, additional, Patel, Biraj, additional, Aghaebrahim, Amin, additional, Sauvageau, Eric, additional, Bhuva, Parita, additional, Soomro, Jazba, additional, Demchuk, Andrew M, additional, Thacker, Ike C, additional, Kayan, Yasha, additional, Copelan, Alexander, additional, Nazari, Pouya, additional, Cantrell, Donald Robert, additional, Haussen, Diogo C, additional, Al-Bayati, Alhamza R, additional, Mohammaden, Mahmoud, additional, Pisani, Leonardo, additional, Rodrigues, Gabriel Martins, additional, Puri, Ajit S, additional, Entwistle, John, additional, Meves, Alexander, additional, Arturo Larco, Jorge L, additional, Savastano, Luis, additional, Cloft, Harry J, additional, Kallmes, David F, additional, Doyle, Karen M, additional, and Brinjikji, Waleed, additional

Published
2021
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32. Per pass analysis of thrombus composition retrieved by mechanical thrombectomy

Author

Abbasi, Mehdi, primary, Kvamme, Peter, additional, Layton, Kennith F, additional, Hanel, Ricardo A, additional, Almekhlafi, Mohammed A, additional, Delgado, Josser E, additional, Pereira, Vitor M, additional, Patel, Biraj M, additional, Jahromi, Babak S, additional, Yoo, Albert J, additional, Nogueira, Raul G, additional, Gounis, Matthew J, additional, Fitzgerald, Seán, additional, Mereuta, Oana M, additional, Dai, Daying, additional, Kadirvel, Ramanathan, additional, Kallmes, David F, additional, Doyle, Karen M, additional, Savastano, Luis E, additional, Cloft, Harry J, additional, Liu, Yang, additional, Thacker, Ike C, additional, Aghaebrahim, Amin, additional, Sauvageau, Eric, additional, Demchuk, Andrew M, additional, Kayan, Yasha, additional, Copelan, Alexander Z, additional, Entwistle, John, additional, Nazari, Pouya, additional, Cantrell, Donald Robert, additional, Bhuva, Parita, additional, Soomro, Jazba, additional, Haussen, Diogo C, additional, Al-Bayati, Alhamza, additional, Mohammaden, Mahmoud, additional, Pisani, Leonardo, additional, Rodrigues, Gabriel, additional, Puri, Ajit S, additional, and Brinjikji, Waleed, additional

Published
2021
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33. High-resolution scanning electron microscopy for the analysis of 3D ultrastructure of clots in acute ischemic stroke

Author

Mereuta, Oana Madalina, Fitzgerald, Seán, Christensen, Trace A, Jaspersen, Adam L, Dai, Daying, Abbasi, Mehdi, Puttappa, Tejaswini, Kadirvel, Ram, Kallmes, David F, Doyle, Karen, and Brinjikji, Waleed

Subjects
Stroke, Erythrocytes, Microscopy, Electron, Scanning, Humans, Thrombosis, Article, Brain Ischemia, Ischemic Stroke, Thrombectomy
Abstract

BACKGROUND: Characterization of acute ischemic stroke (AIS) clots has typically focused on two dimensional histological analysis of the thrombus. The three dimensional (3D) architecture and distribution of components within emboli have not been fully investigated. The aim of this study was to examine the composition and microstructure of AIS clots using histology and serial block-face scanning electron microscopy (SBFSEM). METHODS: As part of the multi-institutional STRIP registry, ten consecutive AIS emboli were collected from ten patients treated by mechanical thrombectomy. Histological and immunohistochemical analysis was performed to determine clot composition. SBFSEM was used to assess ultrastructural organization of clots and specific features of individual components. RESULTS: Quantification of Martius Scarlett Blue stain identified fibrin (44.4%) and red blood cells (RBC, 32.6%) as main components. Immunohistochemistry showed a mean platelet and von Willebrand content of 23.9% and 11.8%, respectively. The 3D organization of emboli varied greatly depending on the region analyzed. RBC-rich areas were composed of tightly packed RBC deformed into polyhedrocytes with scant fibrin fibers interwoven between cells. Regions with mixed composition showed thick fibrin fibers along with platelets, white blood cells and RBC clusters. Fibrin-rich areas contained dense fibrin masses with sparse RBC. In three cases, the fibrin formed a grid-like or a sponge-like pattern likely due to thrombolytic treatment. Segmentation showed that fibrin fibers were thinner and less densely packed in these cases. CONCLUSIONS: 3D-SEM provides novel and potentially clinically relevant information on clot components and ultrastructure which may help to inform thrombolytic treatment and medical device design.

Published
2020

34. Novel Focal Therapeutic Hypothermia Device for Treatment of Acute Neurologic Injury: Large Animal Safety and Efficacy Trial.

Author

Carlstrom, Lucas P., Perry, Avital, Graffeo, Christopher S., Dai, Daying, Ding, Yong H., Jakaitis, Daniel R., Lu, Aiming, Rodgers, Seth, Kreck, Thomas, Hoofer, Kelly, Gorny, Krzysztof R., Kadirvel, Ramanathan, and Kallmes, David F.

Subjects
THERAPEUTIC hypothermia, CEREBRAL anoxia-ischemia, WOUNDS & injuries, BODY temperature, ARTERIAL occlusions, SAFETY
Abstract

Objective  Therapeutic hypothermia is a potentially powerful and controversial clinical tool for neuroprotection following acute neurologic pathology, particularly vascular injury. Indeed, therapeutic hypothermia remains a standard of care for postcardiac arrest ischemia and acute neonatal hypoxic-ischemic encephalopathy, improving both survival and outcomes. Although therapeutic hypothermia remains promising for cellular and systems-based neuronal protection in other neurologic injury states, the systemic side effects have limited clinical utility, confounded analysis of potential neurologic benefits, and precluded the completion of meaningful clinical trials. Methods  To address such limitations, we developed and tested a novel, minimally invasive, neurocritical care device that employs continuous circulation of cold saline through the pharyngeal region to deliver focal cerebrovascular cooling. We conducted a preclinical safety and efficacy trial in six adult porcine animals to assess the validity and functionality of the NeuroSave device, and assess cooling potential following middle cerebral artery occlusion (n  = 2). Results  NeuroSave consistently lowered brain parenchymal temperature by a median of 9°C relative to core temperature within 60 minutes of initiation, including in ischemic cerebral parenchyma. The core body temperature experienced a maximal reduction of 2°C, or 5% of body temperature, with no associated adverse effects identified. Conclusion  The present study uses a large animal preclinical model to demonstrate the safety and efficacy of a novel, noninvasive device for the induction of robust and systemically safe hypothermia within the brain. [ABSTRACT FROM AUTHOR]

Published
2022
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35. Histological evaluation of acute ischemic stroke thrombi may indicate the occurrence of vessel wall injury during mechanical thrombectomy.

Author

Mereuta, Oana Madalina, Abbasi, Mehdi, Fitzgerald, Seán, Dai, Daying, Kadirvel, Ram, Hanel, Ricardo A., Yoo, Albert J., Almekhlafi, Mohammed A., Layton, Kennith F., Delgado Almandoz, Josser E., Kvamme, Peter, Mendes Pereira, Vitor, Jahromi, Babak S., Nogueira, Raul G., Gounis, Matthew J., Patel, Biraj, Aghaebrahim, Amin, Sauvageau, Eric, Bhuva, Parita, and Soomro, Jazba

Subjects
VASCULAR smooth muscle analysis, CEREBRAL embolism & thrombosis, BIOMARKERS, REPORTING of diseases, ENDOTHELIAL cells, RESEARCH, BLOOD vessels, STAINS & staining (Microscopy), ISCHEMIC stroke, IMMUNOHISTOCHEMISTRY, BLOOD platelets, REVASCULARIZATION (Surgery), SURGERY, PATIENTS, THROMBOLYTIC therapy, HEALTH outcome assessment, VEIN surgery, RISK assessment, THROMBECTOMY, HISTOLOGICAL techniques, STATISTICAL correlation, ERYTHROCYTES
Abstract

Background Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine. Objective To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots. Methods As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells). Results MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/ other (p=0.005*) than non-VWI clots suggesting soft thrombus material. Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1-4] vs 1 [1-3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI. Conclusions Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device. [ABSTRACT FROM AUTHOR]

Published
2022
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36. L-Arginine reduces downstream vascular contractility after flow-diverting device deployment: A preliminary study in a rabbit model.

Author

Ayers-Ringler, Jennifer, Kolumam Parameswaran, Praveen, Khashim, Zenith, Dai, Daying, Ding, Yong-Hong, Kallmes, David F, and Kadirvel, Ramanathan

Subjects
ARGININE, INTRACRANIAL aneurysms, WESTERN immunoblotting, VASCULAR smooth muscle, RABBITS, DRINKING water
Abstract

Background: Flow diverters (FDs) are an effective treatment for intracranial aneurysms, though not free from hemorrhagic complications. A previous study demonstrated increased vascular contractility after FD-implantation as a potential mechanism of distal complications. Our study aimed to investigate whether L-arginine medication affects vascular contractility following FD deployment in a rabbit model. Methods: FDs were implanted in the aorta of normal rabbits (+FD, n = 10), with sham-operated aorta as controls (n = 5). L-Arginine was given in the drinking water (2.25% L-arginine hydrochloride) of half of the +FD animals (+FD/+Arg). Force contraction vascular contractility studies were performed on the aortic rings proximal and distal to the FD using an organ bath. Total eNOS, eNOS(pS1177), eNOS(pT495), COX-2, and S100A4 were quantified by western analysis on total protein lysates from aortic segments, normalizing to GAPDH. Results: Mean vascular contractility was 53% higher in distal relative to proximal aortic segments (P = 0.0038) in +FD animals, but were not significantly different in +FD/+Arg animals, or in sham-operated controls. The +FD animals expressed significantly reduced levels of eNOS(pS1177) than sham-operated controls (P = 0.0335), while both the +FD and +FD/+Arg groups had reduced levels of eNOS(pT495) relative to sham-operated controls (P = 0.0331 and P = 0.0311, respectively). Conclusion: These results suggest that L-arginine medication reduces distal vascular contractility after FD treatment via nitric oxide production and thus might mitigate risk for downstream complications. [ABSTRACT FROM AUTHOR]

Published
2022
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37. Association between clot composition and stroke origin in mechanical thrombectomy patients: analysis of the Stroke Thromboembolism Registry of Imaging and Pathology

Author

Brinjikji, Waleed, primary, Nogueira, Raul G, additional, Kvamme, Peter, additional, Layton, Kennith F, additional, Delgado Almandoz, Josser E, additional, Hanel, Ricardo A, additional, Mendes Pereira, Vitor, additional, Almekhlafi, Mohammed A, additional, Yoo, Albert J, additional, Jahromi, Babak S, additional, Gounis, Matthew J, additional, Patel, Biraj, additional, Abbasi, Mehdi, additional, Fitzgerald, Seán, additional, Mereuta, Oana Madalina, additional, Dai, Daying, additional, Kadirvel, Ramanathan, additional, Doyle, Karen, additional, Savastano, Luis, additional, Cloft, Harry J, additional, Haussen, Diogo C, additional, Al-Bayati, Alhamza R, additional, Mohammaden, Mahmoud H, additional, Pisani, Leonardo, additional, Rodrigues, Gabriel Martins, additional, Thacker, Ike C, additional, Kayan, Yasha, additional, Copelan, Alexander, additional, Aghaebrahim, Amin, additional, Sauvageau, Eric, additional, Demchuk, Andrew M, additional, Bhuva, Parita, additional, Soomro, Jazba, additional, Nazari, Pouya, additional, Cantrell, Donald Robert, additional, Puri, Ajit S, additional, Entwistle, John, additional, Polley, Eric C, additional, and Kallmes, David F, additional

Published
2021
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38. Novel Focal Therapeutic Hypothermia Device for Treatment of Acute Neurologic Injury: Large Animal Safety and Efficacy Trial

Author

Carlstrom, Lucas P., additional, Perry, Avital, additional, Graffeo, Christopher S., additional, Dai, Daying, additional, Ding, Yong H., additional, Jakaitis, Daniel R., additional, Lu, Aiming, additional, Rodgers, Seth, additional, Kreck, Thomas, additional, Hoofer, Kelly, additional, Gorny, Krzysztof R., additional, Kadirvel, Ramanathan, additional, and Kallmes, David F., additional

Published
2021
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40. A novel rabbit thromboembolic occlusion model

Author

Ding, Yong-Hong, primary, Fitzgerald, Seán, additional, Liu, Yang, additional, Dai, Daying, additional, Jakaitis, Daniel, additional, Doyle, Karen, additional, Brinjikji, Waleed, additional, Kallmes, David F, additional, Savastano, Luis, additional, and Kadirvel, Ramanathan, additional

Published
2021
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47. High-resolution scanning electron microscopy for the analysis of three-dimensional ultrastructure of clots in acute ischemic stroke

Author

Mereuta, Oana Madalina, primary, Fitzgerald, Seán, additional, Christensen, Trace A, additional, Jaspersen, Adam L, additional, Dai, Daying, additional, Abbasi, Mehdi, additional, Puttappa, Tejaswini, additional, Kadirvel, Ram, additional, Kallmes, David F, additional, Doyle, Karen M, additional, and Brinjikji, Waleed, additional

Published
2020
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