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Translational Stroke Research

Saadat Kamran, Abdul Salam, Naveed Akhtar, Ayman Alboudi, Kainat Kamran, Rajvir Singh, Numan Amir, Jihad Inshasi, Uwais Qidwai, Rayaz A Malik, Ashfaq Shuaib
In patients with malignant middle cerebral artery (MMCA) stroke, a vital clinically relevant question is determination of the speed with which infarction evolves to select the time for decompressive hemicraniectomy [DHC]. A retrospective, multicenter cross-sectional study of patients referred for DHC, based on the criteria of randomized controlled trials, was undertaken to identify factors for selecting the timing of DHC in MMCA stroke, stratified by time [< 48, 48-72, > 72 h]. Infarction volume and infarct growth rate [IGR] were measured on all CT scans...
March 6, 2018: Translational Stroke Research
Tomáš Dorňák, Michal Král, Zuzana Sedláčková, Daniel Šaňák, Eva Čecháková, Petra Divišová, Jana Zapletalová, Petr Kaňovský
In the original publication of the article, there was a switched order of author names.
March 5, 2018: Translational Stroke Research
Lin Liu, Hui Yuan, Yanhua Yi, Edward C Koellhoffer, Yashasvee Munshi, Fan Bu, Yi Zhang, Zhenggang Zhang, Louise D McCullough, Jun Li
Neurite plasticity is a critical aspect of brain functional recovery after stroke. Emerging data suggest that Ras-related C3 botulinum toxin substrate 1 (Rac1) plays a central role in axonal regeneration in the injured brain, specifically by stimulating neuronal intrinsic growth and counteracting the growth inhibitory signaling that leads to growth cone collapse. Therefore, we investigated the functional role of Rac1 in axonal regeneration after stroke.Delayed treatment with a specific Rac1 inhibitor, NSC 23766, worsened functional recovery, which was assessed by the pellet reaching test from day 14 to day 28 after stroke...
February 24, 2018: Translational Stroke Research
William M Armstead, Hugh Hekierski, Philip Pastor, Serge Yarovoi, Abd Al-Roof Higazi, Douglas B Cines
The sole FDA-approved drug treatment for ischemic stroke is tissue-type plasminogen activator (tPA). However, upregulation of JNK mitogen-activated protein kinase (MAPK) and endothelin 1 (ET-1) by tPA after stroke contributes to impaired cerebrovascular autoregulation. Wild-type (wt) tPA can bind to the lipoprotein-related receptor (LRP), which mediates vasodilation, or NMDA receptors (NMDA-Rs), exacerbating vasoconstriction. Elevations in IL-6, a marker of inflammation that accompanies stroke, are reported to be an adverse prognostic factor...
February 23, 2018: Translational Stroke Research
Nagarajesh Gorlamandala, Jasneet Parmar, Amanda J Craig, John M Power, Andrew J Moorhouse, Arun V Krishnan, Gary D Housley
It is generally accepted that the cerebellum is particularly vulnerable to ischaemic injury, and this may contribute to the high mortality arising from posterior circulation strokes. However, this has not been systematically examined in an animal model. This study compared the development and resolution of matched photothrombotic microvascular infarcts in the cerebellar and cerebral cortices in adult 129/SvEv mice of both sexes. The photothrombotic lesions were made using tail vein injection of Rose Bengal with a 532 nm laser projected onto a 2 mm diameter aperture over the target region of the brain (with skull thinning)...
February 17, 2018: Translational Stroke Research
Kinga G Blecharz-Lang, Josephin Wagner, Alexa Fries, Melina Nieminen-Kelhä, Jörg Rösner, Ulf C Schneider, Peter Vajkoczy
Compromised blood-brain barrier (BBB) by dysregulation of cellular junctions is a hallmark of many cerebrovascular disorders due to the pro-inflammatory cytokines action. Interleukin 6 (IL6) is implicated in inflammatory processes and in secondary brain injury after subarachnoid hemorrhage (SAH) but its role in the maintenance of cerebral endothelium still requires a precise elucidation. Although IL6 has been shown to exert pro-inflammatory action on brain microvascular endothelial cells (ECs), the expression of one of the IL6 receptors, the IL6R is controversially discussed...
February 10, 2018: Translational Stroke Research
Gaby U Enzmann, Sofia Pavlidou, Markus Vaas, Jan Klohs, Britta Engelhardt
Accumulation of neutrophils in the brain is a hallmark of cerebral ischemia and considered central in exacerbating tissue injury. Intercellular adhesion molecule (ICAM)-1 is upregulated on brain endothelial cells after ischemic stroke and considered pivotal in neutrophil recruitment as ICAM-1-deficient mouse lines were found protected from experimental stroke. Translation of therapeutic inhibition of ICAM-1 into the clinic however failed. This prompted us to investigate stroke pathogenesis in Icam1tm1Alb C57BL/6 mutants, a true ICAM-1null mouse line...
February 4, 2018: Translational Stroke Research
Mariam Alaverdashvili, Sally Caine, Xue Li, Mark J Hackett, Michael P Bradley, Helen Nichol, Phyllis G Paterson
Protein-energy malnutrition (PEM) pre-existing at stroke onset is believed to worsen functional outcome, yet the underlying mechanisms are not fully understood. Since brain inflammation is an important modulator of neurological recovery after stroke, we explored the impact of PEM on neuroinflammation in the acute period in relation to stroke-initiated sensori-motor abnormalities. Adult rats were fed a low-protein (LP) or normal protein (NP) diet for 28 days before inducing photothrombotic stroke (St) in the forelimb region of the motor cortex or sham surgery; the diets continued for 3 days after the stroke...
February 3, 2018: Translational Stroke Research
A M Penn, V Saly, A Trivedi, M L Lesperance, K Votova, A M Jackson, N S Croteau, R F Balshaw, M B Bibok, D S Smith, K K Lam, J Morrison, L Lu, S B Coutts, C H Borchers
A diagnostic blood test for stroke is desirable but will likely require multiple proteins rather than a single "troponin." Validating large protein panels requires large patient numbers. Mass spectrometry (MS) is a cost-effective tool for this task. We compared differences in the abundance of 147 protein markers to distinguish 20 acute cerebrovascular syndrome (ACVS) patients who presented to the Emergency Department of one urban hospital within < 24 h from onset) and from 20 control patients who were enrolled via an outpatient neurology clinic...
January 24, 2018: Translational Stroke Research
Devin William McBride, Guangyong Wu, Derek Nowrangi, Jerry J Flores, Liang Hui, Paul R Krafft, John H Zhang
Most large vessel stroke patients have permanent occlusion, for which there are no current treatment options. Recent case studies have indicated delayed recanalization, that is recanalization outside of the 6-h treatment window, may lead to improved outcome. We hypothesized that delayed recanalization will restore cerebral blood flow, leading to improved function in rats. Male SD rats were subjected to pMCAO or sham surgery. Delayed recanalization was performed on either day 3, 7, or 14 after pMCAO in a subset of animals...
January 21, 2018: Translational Stroke Research
Dorňák Tomáš, Král Michal, Sedláčková Zuzana, Šaňák Daniel, Čecháková Eva, Divišová Petra, Zapletalová Jana, Kaňovský Petr
Intravenous thrombolysis (IVT) is a standard treatment for anterior (ACS) and posterior circulation stroke (PCS). However, due to the low occurrence of PCS and of intracranial hemorrhage (ICH) in PCS, the knowledge about ICH predictors following IVT in PCS is sparse. Our aim was to identify predictors for ICH following IVT in PCS. The set consisted of 1281 consecutive ischemic stroke (IS) patients treated with IVT, out of which 158 (103 males; mean age 65.6 ± 12.3 years) had PCS. Collected data include baseline characteristics, common stroke risk factors, pre-medication, stroke severity, admission blood glucose level, blood pressure and treatment with intravenous antihypertensive therapy before and during IVT, occlusion of arteries, recanalization rate, time to treatment, and clinical outcome at day 90...
January 15, 2018: Translational Stroke Research
Naveed Akhtar, Abdul Salam, Saadat Kamran, Atlantic D'Souza, Yahia Imam, Pablo Garcia Bermejo, Muhammad Faisal Wadiwala, Ahmed Own, Ahmed ElSotouhy, Surjith Vattoth, Paula Bourke, Zain Bhutta, Sujatha Joseph, Mark Santos, Rabia Ali Khan, Ashfaq Shuaib
The author names "Dr. Pablo Garcia Bermejo" and "Dr. Muhammad Faisal Wadiwala" needed to be added as the 6th and 7th authors, respectively. The authors regret this error.
January 13, 2018: Translational Stroke Research
Michael K Schuhmann, Peter Kraft, Michael Bieber, Axel Haarmann, György A Homola, Mirko Pham, Bernhard Nieswandt, Guido Stoll
In acute ischemic stroke (AIS), there is an alarming discrepancy between recanalization rates of up to 70% by combined recombinant tissue-type plasminogen activator (rt-PA) therapy and mechanical thrombectomy, and no clinical benefit in at least every second stroke patient. This is partly due to ischemia/reperfusion (I/R) injury. In a translational approach, we used mice lacking dense- (Unc13d -/- ) or α-granules (Nbeal2 -/- ) and mice after blocking of platelet glycoprotein receptor (GP) Ib conferring protection from I/R injury...
January 10, 2018: Translational Stroke Research
Yiming Xiao, Hassan Rivaz, Hidetoshi Kasuya, Suguru Yokosako, Cristina Mindru, Jeanne Teitelbaum, Denis Sirhan, David Sinclair, Mark Angle, Benjamin W Y Lo
Cerebral hyperperfusion syndrome (CHS) is a complication that can occur after carotid endarterectomy (CEA), the treatment of choice to decrease the subsequent risk of fatal or disabling stroke for patients with symptomatic severe stenosis of the carotid artery. Because of its rarity and complexity, the mechanism of the condition is still unclear, making its prevention via prediction and monitoring challenging. This is especially true during surgery, when multiple factors can induce physiological changes, including blood pressure and baroreceptor functions, which are crucial factors for post-CEA hypertension and CHS...
January 10, 2018: Translational Stroke Research
Jayantee Kalita, Usha K Misra, Rajesh K Singh
We report the burden of risk factors in cerebral venous sinus thrombosis (CVST) and its relationship with the clinical severity, extent of MRI and MRV abnormality, and outcome. One hundred and twenty-eight consecutive patients with CVST were included. Their demographic, presenting symptoms and neurological findings were noted and risk factors of CVST were evaluated. The outcomes were assessed using modified Rankin Scale (mRS). Based on the risk factors, the patients could be categorized as prothrombotic conditions only in 46 (35...
January 10, 2018: Translational Stroke Research
Anil Can, Rose Du
No abstract text is available yet for this article.
January 9, 2018: Translational Stroke Research
Zhaojin Li, Nicole Bishop, Siu-Lung Chan, Marilyn J Cipolla
Although used extensively in stroke research, there is limited knowledge of how 2, 3, 5-triphenyltetrazolium chloride (TTC)-treated rat brain sections are altered and if they can be used for immunohistochemical quantification after staining with TTC. In the present study, we hypothesized that TTC treatment (TTC+) would not interfere with collagen IV immunohistochemical staining compared with non-TTC-treated (TTC-) brain slices. We further hypothesized that there would be no difference in autofluorescence or nonspecific secondary antibody fluorescence between TTC+ and TTC- brain slices...
January 8, 2018: Translational Stroke Research
Rajkumar Verma, Rodney M Ritzel, Joshua Crapser, Brett D Friedler, Louise D McCullough
Sirtuins (Sirt) are a family of NAD+ dependent histone deacetylase (HDAC) proteins implicated in aging, cell cycle regulation, and metabolism. These proteins are involved in the epigenetic modification of neuromodulatory proteins after strokevia acetylation/deacetylation. The specific role of Sirt3, a mitochondrial sirtuin, in post-stroke injury has been relatively unexplored. Using male Sirt3 knockout (KO) mice and wild-type littermates (WT), we show that Sirt3 KO mice show significant neuroprotection at 3 days after ischemia/reperfusion (I/R) or stroke injury...
January 4, 2018: Translational Stroke Research
Eunhee Kim, Jiwon Yang, Keun Woo Park, Sunghee Cho
In light of repeated translational failures with preclinical neuroprotection-based strategies, this preclinical study reevaluates brain swelling as an important pathological event in diabetic stroke and investigates underlying mechanism of the comorbidity-enhanced brain edema formation. Type 2 (mild), type 1 (moderate), and mixed type 1/2 (severe) diabetic mice were subjected to transient focal ischemia. Infarct volume, brain swelling, and IgG extravasation were assessed at 3 days post-stroke. Expression of vascular endothelial growth factor (VEGF)-A, endothelial-specific molecule-1 (Esm1), and the VEGF receptor 2 (VEGFR2) was determined in the ischemic brain...
December 30, 2017: Translational Stroke Research
Robin L Webb, Erin E Kaiser, Shelley L Scoville, Tyler A Thompson, Sumbul Fatima, Chirayukumar Pandya, Karishma Sriram, Raymond L Swetenburg, Kumar Vaibhav, Ali S Arbab, Babak Baban, Krishnan M Dhandapani, David C Hess, M N Hoda, Steven L Stice
Over 700 drugs have failed in stroke clinical trials, an unprecedented rate thought to be attributed in part to limited and isolated testing often solely in "young" rodent models and focusing on a single secondary injury mechanism. Here, extracellular vesicles (EVs), nanometer-sized cell signaling particles, were tested in a mouse thromboembolic (TE) stroke model. Neural stem cell (NSC) and mesenchymal stem cell (MSC) EVs derived from the same pluripotent stem cell (PSC) line were evaluated for changes in infarct volume as well as sensorimotor function...
December 28, 2017: Translational Stroke Research
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