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Translational Stroke Research

Di Yu, Marie Hennebelle, Demetrios J Sahlas, Joel Ramirez, Fuqiang Gao, Mario Masellis, Hugo Cogo-Moreira, Richard H Swartz, Nathan Herrmann, Pak Cheung Chan, Jacqueline A Pettersen, Donald T Stuss, Sandra E Black, Ameer Y Taha, Walter Swardfager
White matter hyperintensities (WMH) are presumed to indicate subcortical ischemic vascular disease but their underlying pathobiology remains incompletely understood. The soluble epoxide hydrolase (sEH) enzyme converts anti-inflammatory and vasoactive cytochrome p450-derived polyunsaturated fatty acid epoxides into their less active corresponding diol species. Under the hypothesis that the activity of sEH might be associated with subcortical ischemic vascular disease and vascular cognitive impairment, this study aimed to compare the relative abundance of sEH substrates and products in peripheral blood between patients with extensive WMH (discovered due to transient ischemic attack; n = 29) and healthy elderly with minimal WMH (n = 25)...
November 15, 2018: Translational Stroke Research
Catharina Conzen, Katrin Becker, Walid Albanna, Miriam Weiss, Annika Bach, Nyanda Lushina, André Steimers, Sarah Pinkernell, Hans Clusmann, Ute Lindauer, Gerrit A Schubert
Clinical presentation and neurological outcome in subarachnoid hemorrhage (SAH) is highly variable. Aneurysmal SAH (aSAH) is hallmarked by sudden increase of intracranial pressure (ICP) and acute hypoperfusion contributing to early brain injury (EBI) and worse outcome, while milder or non-aneurysmal SAH with comparable amount of blood are associated with better neurological outcome, possibly due to less dramatic changes in ICP. Acute pressure dynamics may therefore be an important pathophysiological aspect determining neurological complications and outcome...
November 15, 2018: Translational Stroke Research
Annemarie Wentzel, Leoné Malan, Wayne Smith, Roland von Känel, Nicolaas T Malan
Structural and functional similarities exist between the retinal, cerebral and, as previously suggested, the coronary microvasculature. Retinal microvascular structure and functionality (in response to flicker-light-induced-provocation (FLIP)) may relate to coronary artery disease risk and possible stroke risk. We investigated associations between retinal vessel structure, functionality and cardiac stress markers (cardiac troponin T [cTnT], amino-terminal B-type natriuretic peptide [NT-proBNP]) to translate these retina-heart relationships to stroke risk...
November 9, 2018: Translational Stroke Research
Susan L Stevens, Tao Liu, Frances Rena Bahjat, Vladislav A Petyuk, Athena A Schepmoes, Ryan L Sontag, Marina A Gritsenko, Chaochao Wu, Sheng Wang, Anil K Shukla, Jon M Jacobs, Richard D Smith, Karin D Rodland, G Alexander West, Steven G Kohama, Christine Glynn, Mary P Stenzel-Poore
Each year, thousands of patients are at risk of cerebral ischemic injury, due to iatrogenic responses to surgical procedures. Prophylactic treatment of these patients as standard care could minimize potential neurological complications. We have shown that protection of brain tissue, in a non-human primate model of cerebral ischemic injury, is possible through pharmacological preconditioning using the immune activator D192935. We postulate that preconditioning with D192935 results in neuroprotective reprogramming that is evident in the brain following experimentally induced cerebral ischemia...
October 19, 2018: Translational Stroke Research
Gyeong Joon Moon, Ji Hee Sung, Dong Hee Kim, Eun Hee Kim, Yeon Hee Cho, Jeong Pyo Son, Jae Min Cha, Oh Young Bang
Mesenchymal stem cells (MSCs) exert their therapeutic capability through a variety of bioactive substances, including trophic factors, microRNAs, and extracellular vesicles (EVs) in infarcted tissues. We therefore hypothesized that MSC-derived EVs (MSC-EVs) possess therapeutic molecules similar to MSCs. Moreover, given their nature as nanosized and lipid-shielded particles, the intravenous infusion of MSC-EVs would be advantageous over MSCs as a safer therapeutic approach. In this study, we investigated the biodistribution, therapeutic efficacy, and mode of action of MSC-EVs in a rat stroke model...
October 19, 2018: Translational Stroke Research
Jane A H Masoli, Luke C Pilling, George A Kuchel, David Melzer
No abstract text is available yet for this article.
October 18, 2018: Translational Stroke Research
Hongwei Liu, Ya Hua, Richard F Keep, Guohua Xi
Ceruloplasmin (CP) is an essential ferroxidase that is involved in maintaining iron homeostasis by oxidizing toxic ferrous iron (Fe2+ ) to less-toxic ferric iron (Fe3+ ). CP has been well studied in many neurodegenerative diseases, but there has not been an in-depth investigation in intracerebral hemorrhage (ICH). This research investigated brain CP expression in rats after ICH and the effect of CP on Fe2+ -induced brain injury. This study had two parts: first, rats had injection of autologous blood into the right basal ganglia and the time course of CP expression in the brain examined (protein and mRNA)...
October 12, 2018: Translational Stroke Research
Samuel G Thorpe, Corey M Thibeault, Seth J Wilk, Michael O'Brien, Nicolas Canac, Mina Ranjbaran, Christian Devlin, Thomas Devlin, Robert B Hamilton
Despite being a conveniently portable technology for stroke assessment, Transcranial Doppler ultrasound (TCD) remains widely underutilized due to complex training requirements necessary to reliably obtain and interpret cerebral blood flow velocity (CBFV) waveforms. The validation of objective TCD metrics for large vessel occlusion (LVO) represents a first critical step toward enabling use by less formally trained personnel. In this work, we assess the diagnostic utility, relative to current standard CT angiography (CTA), of a novel TCD-derived biomarker for detecting LVO...
October 6, 2018: Translational Stroke Research
Michael R Williamson, Cassandra M Wilkinson, Kristen Dietrich, Frederick Colbourne
Increased intracranial pressure (ICP) after stroke can lead to poor outcome and death. Novel treatments to combat ICP rises are needed. The carbonic anhydrase inhibitor acetazolamide diminishes cerebrospinal fluid (CSF) production, reduces ICP in healthy animals, and is beneficial for idiopathic intracranial hypertension patients. We tested whether acetazolamide mitigates ICP elevations by presumably decreasing CSF volume after collagenase-induced striatal hemorrhage in rats. We confirmed that acetazolamide did not adversely affect hematoma formation in this model or physiological variables, such as temperature...
September 17, 2018: Translational Stroke Research
Elena Jiménez-Xarrié, Belén Pérez, Ana Paula Dantas, Lídia Puertas-Umbert, Joan Martí-Fabregas, Ángel Chamorro, Anna Maria Planas, Elisabet Vila, Francesc Jiménez-Altayó
Hypertension is the most important modifiable risk factor for stroke and is associated with poorer post-stroke outcomes. The antioxidant uric acid is protective in experimental normotensive ischaemic stroke. However, it is unknown whether this treatment exerts long-term protection in hypertension. We aimed to evaluate the impact of transient intraluminal middle cerebral artery (MCA) occlusion (90 min)/reperfusion (1-15 days) on brain and vascular damage progression in adult male Wistar-Kyoto (WKY; n = 36) and spontaneously hypertensive (SHR; n = 37) rats treated (i...
September 15, 2018: Translational Stroke Research
Serge Marbacher, Basil Grüter, Salome Schöpf, Davide Croci, Edin Nevzati, Donato D'Alonzo, Jacqueline Lattmann, Tabitha Roth, Benjamin Bircher, Christina Wolfert, Carl Muroi, Gilles Dutilh, Hans Rudolf Widmer, Javier Fandino
In preclinical models, modification of experimental parameters associated with techniques of inducing subarachnoid hemorrhage (SAH) can greatly affect outcomes. To analyze how parameter choice affects the relevance and comparability of findings, we systematically reviewed 765 experimental studies of in vivo animal SAH models (2000-2014). During the last decade, we found marked increases in publications using smaller species and models for simulating acute events after SAH. Overall, the fewer types of species and models used did not correlate with an increased standardization in the experimental characteristics and procedures...
September 12, 2018: Translational Stroke Research
Xiang Li, Dongxia Feng, Gang Chen
No abstract text is available yet for this article.
September 11, 2018: Translational Stroke Research
Shoa-Lin Lin, Jwu-Lai Yeh, Pei-Chia Tsai, Tsung-Hsien Chang, Wei-Chun Huang, Song-Tay Lee, Michael Wassler, Yong-Jian Geng, Erna Sulistyowati
Extracellular superoxide dismutase (EC-SOD) has been implicated in regulation of vascular function but its underlying molecular mechanism is largely unknown. These two-step experiments investigate whether hemagglutinating virus of Japan envelope (HVJ-E) vector-mediated EC-SOD gene delivery might protect against neointima formation, vascular inflammation, and reactive oxygen species (ROS) generation, and also explore cell growth signaling pathways. The first in-vitro experiment was performed to assess the transfection efficacy and safety of HVJ-E compared to lipofectamine®...
September 6, 2018: Translational Stroke Research
YaXing Gui, ZhongPing Xu, Tao Jin, LiSan Zhang, LiLi Chen, Bin Hong, Fei Xie, Wen Lv, XingYue Hu
There is no effective biological method to classify ischemic stroke subtypes. In this study, we first performed a systematical gene array study on serum microRNAs with different ischemic stroke subtypes including 13 normal control subjects (NCs) and 87 ischemic stroke (IS) patients including 23 cardioembolism (CARD), 26 large artery atherosclerosis (LAA), 27 lacunar infarct (LAC), and 11 stroke of undetermined etiology (SUE). Validation was performed by using an independent cohort of 20 NCs and 85 IS patients including 28 CARD, 23 LAA, 18 LAC, and 16 SUE...
September 4, 2018: Translational Stroke Research
Weixin Si, Pingping He, Yi Wang, Yu Fu, Xin Li, Xiaoru Lin, Fenghua Chen, Guodong Cao, Hong Zhang
The terminal complement complex C5b-9 plays an important role in acute ischemic stroke (AIS) and carotid atherosclerosis. However, the associations between serum C5b-9, the severity and outcome of AIS, and the stability of carotid plaques have not been well investigated. In this clinical study, 70 patients with AIS and 70 healthy controls were enrolled. Serum C5b-9 levels at 72 h after stroke onset were measured by enzyme-linked immunosorbent assay (ELISA). Infarct size, the National Institutes of Health Stroke Scale (NIHSS), the 90-day modified Rankin Scale (mRS), and carotid plaque and stenosis were evaluated...
September 1, 2018: Translational Stroke Research
Giovanni Pietrogrande, Katarzyna Zalewska, Zidan Zhao, Sarah J Johnson, Michael Nilsson, Frederick R Walker
Low oxygen post conditioning (LOPC) has shown promising results in terms of neuroprotection after stroke, but the effects on motor function have not been considered. Cortical stroke targeting the motor and sensory cortex was induced by photothrombotic occlusion and after 48 h allocated to LOPC (11% O2 ) for 2 weeks. Motor impairment was assessed using the cylinder and grid walk tests during the exposure period and for two further weeks upon completion of the intervention. Neuroprotection was evaluated by histological and molecular analysis at two time points...
August 28, 2018: Translational Stroke Research
Aswathi Gopalakrishnan, Sahadev A Shankarappa, G K Rajanikant
Chronic brain injury following cerebral ischemia is a severe debilitating neurological condition, where clinical intervention is well known to decrease morbidity and mortality. Despite the development of several therapeutic strategies, clinical outcome in the majority of patients could be better improved, since many still face life-long neurological deficits. Among the several strategic options that are currently being pursued, tissue engineering provides much promise for neural tissue salvage and regeneration in brain ischemia...
August 27, 2018: Translational Stroke Research
Sheng Chen, Shuhao Mei, Yujie Luo, Hemmings Wu, Jianmin Zhang, Junming Zhu
Stroke is one of the leading causes of death worldwide and therapies are limited. According to the mechanisms underlying stroke, direct cell demise, destruction of organelles, blood-brain barrier disruption, neuroinflammation are potential therapeutic targets. Gasdermin (GSDM) family is a series of recently discovered proteins, which acts as the executor of pyroptosis and protagonist of membrane pore formation. It can be cleaved by inflammatory caspases that are activated by multi-protein complexes, named as inflammasomes, and divided into two domains...
December 2018: Translational Stroke Research
Jinwei Pang, Jianhua Peng, Nathanael Matei, Ping Yang, Li Kuai, Yue Wu, Ligang Chen, Michael P Vitek, Fengqiao Li, Xiaochuan Sun, John H Zhang, Yong Jiang
Subarachnoid hemorrhage (SAH) is a neurologically destructive stroke in which early brain injury (EBI) plays a pivotal role in poor patient outcomes. Expanding upon our previous work, multiple techniques and methods were used in this preclinical study to further elucidate the mechanisms underlying the beneficial effects of apolipoprotein E (ApoE) against EBI after SAH in murine apolipoprotein E gene-knockout mice (Apoe-/- , KO) and wild-type mice (WT) on a C57BL/6J background. We reported that Apoe deficiency resulted in a more extensive EBI at 48 h after SAH in mice demonstrated by MRI scanning and immunohistochemical staining and exhibited more extensive white matter injury and neuronal apoptosis than WT mice...
December 2018: Translational Stroke Research
Wei Cai, Sanxin Liu, Mengyan Hu, Xiaobo Sun, Wei Qiu, Songguo Zheng, Xiaoming Hu, Zhengqi Lu
Systemic docosahexaenoic acid (DHA) has been explored as a clinically feasible protectant in stroke models. However, the mechanism for DHA-afforded neuroprotection remains elusive. Transient middle cerebral artery occlusion (tMCAO) was induced for 1 h. DHA (i.p., 10 mg/kg) was administered immediately after reperfusion and repeated daily for 3 days. Stroke outcomes, systemic inflammatory status, and microglia/macrophage phenotypic alterations were assessed 3 days after stroke. Macrophage depletion was induced by clodronate liposomes injection...
December 2018: Translational Stroke Research
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