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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
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...
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
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...
September 10, 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
Laura Otero-Ortega, Fernando Laso-García, MariCarmen Gómez-de Frutos, Blanca Fuentes, Luke Diekhorst, Exuperio Díez-Tejedor, María Gutiérrez-Fernández
Approximately, 16 million strokes occur worldwide each year, causing 6 million deaths and considerable disability, implying an enormous social, individual health, and economic burden. Due to this high incidence, strategies to promote stroke recovery are urgently needed. Research into new therapeutic approaches for stroke has determined that intravenous administration of mesenchymal stem cells (MSCs) is a good strategy to improve recovery by amplifying mechanisms implicated in brain plasticity. Recent studies have demonstrated the efficacy of MSCs in stroke, with no need for them to reach the area of brain injury...
August 13, 2018: Translational Stroke Research
Simona Lattanzi, Francesco Brigo, Eugen Trinka, Claudia Cagnetti, Mario Di Napoli, Mauro Silvestrini
Spontaneous intracerebral hemorrhage (ICH) accounts for approximately 10 to 30% of all acute cerebrovascular events, and it is the type of stroke associated with the highest rates of mortality and residual disability. The inflammatory response is early triggered by hematoma components and can enhance the damage within the hemorrhagic brain. Assessment of peripheral biomarkers of inflammation could contribute to increase knowledge about some of the mechanisms involved in the ICH-induced injury and yield information on the disease course...
August 8, 2018: Translational Stroke Research
Ellen N Sutter, Anna E Mattlage, Marghuretta D Bland, Kendra M Cherry-Allen, Elinor Harrison, Swati M Surkar, Jeffrey M Gidday, Ling Chen, Tamara Hershey, Jin-Moo Lee, Catherine E Lang
Remote limb ischemic conditioning (RLIC) is a clinically feasible method of promoting tissue protection against subsequent ischemic insult. Recent findings from our lab demonstrated that RLIC robustly enhances motor learning in young, healthy humans. The next step is to determine which individuals would receive maximum benefit from RLIC before applying these findings to clinical rehabilitation populations such as stroke. Numerous factors, such as age, sex, body mass index (BMI), and cardiovascular comorbidities may influence the response...
August 7, 2018: Translational Stroke Research
Wenshu Luo, Tao Liu, Shanshan Li, Hongmei Wen, Fenghua Zhou, Ross Zafonte, Xun Luo, Minghzu Xu, Randie Black-Schaffer, Lisa J Wood, Yulong Wang, Qing Mei Wang
Brain-derived neurotrophic factor (BDNF) plays an important role in neuroplasticity and neurogenesis following ischemic and non-ischemic brain injury. The predictive value of BDNF for short-term outcome after stroke is controversial. The objective of this study was to investigate the relationship among serum BDNF level, fractional anisotropy (FA), and functional outcome during post-acute stroke rehabilitation. Serum BDNF levels were measured on admission to an acute inpatient rehabilitation hospital. The primary functional outcome was functional independence measure (FIM) motor subscore at discharge...
August 3, 2018: Translational Stroke Research
Manuel Navarro-Oviedo, Carmen Roncal, Agustina Salicio, Miriam Belzunce, Obdulia Rabal, Estefanía Toledo, Beatriz Zandio, Jose A Rodríguez, Jose A Páramo, Roberto Muñoz, Josune Orbe
Diabetes is an important risk factor for ischemic stroke (IS). Tissue-type plasminogen activator (tPA) has been associated with less successful revascularization and poor functional outcome in diabetes. We assessed whether a new thrombolytic strategy based on MMP10 was more effective than tPA in a murine IS model of streptozotocin (STZ)-induced diabetes. Wild-type mice were administered a single dose of streptozotocin (STZ) (180 mg/kg) to develop STZ-induced diabetes mellitus. Two weeks later, IS was induced by thrombin injection into the middle cerebral artery and the effect of recombinant MMP10 (6...
July 27, 2018: Translational Stroke Research
Eva A Rocha, Mehmet Akif Topcuoglu, Aneesh B Singhal
Post-stroke recrudescence (PSR) usually occurs in the setting of infection, hypotension, hyponatremia, insomnia or stress, and benzodiazepine use. Animal studies have suggested an infection-related immunologic mechanism for PSR. This retrospective study was designed to assess whether infection-triggered PSR is related to a prior infection during the index stroke. We identified 95 patients admitted to Massachusetts General Hospital from 2000 to 2015 with post-stroke recrudescence who had adequate medical record information concerning the index stroke...
July 25, 2018: Translational Stroke Research
Hidenori Suzuki, Yoshinari Nakatsuka, Ryuta Yasuda, Masato Shiba, Yoichi Miura, Mio Terashima, Yume Suzuki, Koichi Hakozaki, Fuki Goto, Naoki Toma
Cilostazol is a selective inhibitor of phosphodiesterase type III that downregulates tenascin-C (TNC), a matricellular protein, which may cause delayed cerebral infarction after aneurysmal subarachnoid hemorrhage (SAH). The authors increased the dosage and evaluated the dose-dependent effects of cilostazol on delayed cerebral infarction and outcomes in SAH patients. This was a retrospective cohort study in a single center. One hundred fifty-six consecutive SAH patients including 67 patients of admission World Federation of Neurological Surgeons grades IV-V who underwent aneurysmal obliteration within 48 h post-SAH from 2007 to 2017 were analyzed...
July 23, 2018: Translational Stroke Research
Axel Neulen, Simon Meyer, Andreas Kramer, Tobias Pantel, Michael Kosterhon, Svenja Kunzelmann, Hermann Goetz, Serge C Thal
Clinical studies on subarachnoid hemorrhage (SAH) have shown discrepancies between large vessel vasospasm, cerebral perfusion, and clinical outcome. We set out to analyze the contribution of large vessel vasospasm to impaired cerebral perfusion and neurological impairment in a murine model of SAH. SAH was induced in C57BL/6 mice by endovascular filament perforation. Vasospasm was analyzed with microcomputed tomography, cortical perfusion by laser SPECKLE contrast imaging, and functional impairment with a quantitative neuroscore...
July 12, 2018: Translational Stroke Research
Joshua A Santucci, Stephen R Ross, John C Greenert, Faranak Aghaei, Lance Ford, Kimberly M Hollabaugh, Benjamin O Cornwell, Dee H Wu, Bin Zheng, Bradley N Bohnstedt, Bappaditya Ray
Acute phase after aneurysmal subarachnoid hemorrhage (aSAH) is associated with several metabolic derangements including stress-induced hyperglycemia (SIH). The present study is designed to identify objective radiological determinants for SIH to better understand its contributory role in clinical outcomes after aSAH. A computer-aided detection tool was used to segment admission computed tomography (CT) images of aSAH patients to estimate intracranial blood and cerebrospinal fluid volumes. Modified Graeb score (mGS) was used as a semi-quantitative measure to estimate degree of hydrocephalus...
July 11, 2018: Translational Stroke Research
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