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Translational Stroke Research

Ilan Vonderwalde, Ashkan Azimi, Gabrielle Rolvink, Jan-Eric Ahlfors, Molly S Shoichet, Cindi M Morshead
Stroke is one of the leading causes of long-term disability. Cell transplantation is a promising strategy to treat stroke. We explored the efficacy of directly reprogrammed human neural precursor cell (drNPC) transplants to promote functional recovery in a model of focal ischemic stroke in the mouse sensorimotor cortex. We show that drNPCs express neural precursor cell markers and are neurally committed at the time of transplantation. Mice that received drNPC transplants recovered motor function, irrespective of transplant vehicle or recipient sex, and with no correlation to lesion volume or glial scarring...
February 12, 2019: Translational Stroke Research
Hirokazu Koseki, Haruka Miyata, Satoshi Shimo, Nobuhiko Ohno, Kazuma Mifune, Kenjiro Shimano, Kimiko Yamamoto, Kazuhiko Nozaki, Hidetoshi Kasuya, Shuh Narumiya, Tomohiro Aoki
Intracranial aneurysm (IA) usually induced at a bifurcation site of intracranial arteries causes a lethal subarachnoid hemorrhage. Currently, IA is considered as a macrophage-mediated inflammatory disease triggered by a high wall shear stress (WSS) on endothelial cells. However, considered the fact that a high WSS can be observed at every bifurcation site, some other factors are required to develop IAs. We therefore aimed to clarify mechanisms underlying the initiation of IAs using a rat model. We found the transient outward bulging and excessive mechanical stretch at a prospective site of IA formation...
February 8, 2019: Translational Stroke Research
Heling Chu, Chuyi Huang, Jing Dong, Xiaobo Yang, Jun Xiang, Qiang Dong, Yuping Tang
This study aimed to investigate whether serum lactate dehydrogenase (LDH) levels predicted hematoma expansion and poor outcomes in intracerebral hemorrhage (ICH) patients. The differentially expressed proteins between patients with and without hematoma expansion were screened using proteomic analysis. Then the critical value of the target protein was determined by retrospectively analyzing the data from a derivation cohort. A prospective study on the validation cohort of three clinical centers was performed to investigate the association between the target protein and hematoma expansion and poor outcomes (modified Rankin Scale > 3) at 90 days by using univariate and multivariate logistic regression analyses...
January 31, 2019: Translational Stroke Research
Jyoti Gautam, Jeffrey H Miner, Yao Yao
Endothelial cells make laminin-411 and laminin-511. Although laminin-411 is well studied, the role of laminin-511 remains largely unknown due to the embryonic lethality of lama5-/- mutants. In this study, we generated endothelium-specific lama5 conditional knockout (α5-TKO) mice and investigated the biological functions of endothelial lama5 in blood-brain barrier (BBB) maintenance under homeostatic conditions and the pathogenesis of intracerebral hemorrhage (ICH). First, the BBB integrity of α5-TKO mice was measured under homeostatic conditions...
January 29, 2019: Translational Stroke Research
Mark R Etherton, Ona Wu, Anne-Katrin Giese, Arne Lauer, Gregoire Boulouis, Brittany Mills, Lisa Cloonan, Kathleen L Donahue, William Copen, Pamela Schaefer, Natalia S Rost
Chronic white matter structural injury is a risk factor for poor long-term outcomes after acute ischemic stroke (AIS). However, it is unclear how white matter structural injury predisposes to poor outcomes after AIS. To explore this question, in 42 AIS patients with moderate to severe white matter hyperintensity (WMH) burden, we characterized WMH and normal-appearing white matter (NAWM) diffusivity anisotropy metrics in the hemisphere contralateral to acute ischemia in relation to ischemic tissue and early functional outcomes...
January 28, 2019: Translational Stroke Research
Liping Wang, Panting Zhou, Zhihao Mu, Xiaojie Lin, Lu Jiang, Zhuo Cheng, Longlong Luo, Zhiming Xu, Jieli Geng, Yongting Wang, Zhijun Zhang, Guo-Yuan Yang
A rodent model of embolic middle cerebral artery occlusion is used to mimic cerebral embolism in clinical patients. Thrombolytic therapy is the effective treatment for this ischemic injury. However, it is difficult to detect thrombolysis dynamically in living animals. Synchrotron radiation angiography may provide a novel approach to directly monitor the thrombolytic process and assess collateral circulation after embolic stroke. Thirty-six adult Sprague-Dawley rats underwent the embolic stroke model procedure and were then treated with tissue plasminogen activator...
January 24, 2019: Translational Stroke Research
Toshio Fumoto, Masato Naraoka, Takeshi Katagai, Yuchen Li, Norihito Shimamura, Hiroki Ohkuma
Oxidative stress was shown to play a crucial role in the diverse pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Microcirculatory dysfunction is thought to be an important and fundamental pathological change in EBI. However, other than blood-brain barrier (BBB) disruption, the influence of oxidative stress on microvessels remains to be elucidated. The aim of this study was to investigate the role of oxidative stress on microcirculatory integrity in EBI. SAH was induced in male Sprague-Dawley rats using an endovascular perforation technique...
January 9, 2019: Translational Stroke Research
Malgorzata Burek, Anna König, Mareike Lang, Jan Fiedler, Sabrina Oerter, Norbert Roewer, Michael Bohnert, Serge C Thal, Kinga G Blecharz-Lang, Johannes Woitzik, Thomas Thum, Carola Y Förster
Blood-brain barrier (BBB) integrity is one of the important elements of central nervous system (CNS) homeostasis. MicroRNAs (miRs) have been demonstrated to play a role in many CNS disorders such as stroke and traumatic brain injury. MiR-212/132 are highly expressed in the CNS but their role at the BBB has not been characterized yet. Thus, we analyzed the expression of miR-212/132 in hypoxic mouse and human brain microvascular endothelial cells (BMEC) as well as in posttraumatic mouse and human brain tissue and serum exosomes...
January 8, 2019: Translational Stroke Research
Dirk Brämer, Albrecht Günther, Sven Rupprecht, Samuel Nowack, Josephine Adam, Fenja Meyer, Matthias Schwab, Ralf Surber, Otto W Witte, Heike Hoyer, Dirk Hoyer
Stroke-induced immunodepression is a major risk factor for severe infectious complications in the immediate post-stroke period. We investigated the predictive value of heart rate variability (HRV) to identify patients at risk of post-stroke infection, systemic inflammatory response syndrome, or severe sepsis during the post-acute interval from days 3 to 5 after stroke onset. A prospective, observational monocentric cohort study was conducted in a university hospital stroke unit of patients with ischemic infarction in the territory of the middle cerebral artery without an ongoing infection at admission...
January 7, 2019: Translational Stroke Research
Josie C van Kralingen, Aisling McFall, Emily N J Ord, Thomas F Coyle, Maria Bissett, John D McClure, Christopher McCabe, I Mhairi Macrae, Jesse Dawson, Lorraine M Work
Active transport of microRNAs (miRNA) in extracellular vesicles (EV) occurs in disease. Circulating EV-packaged miRNAs in the serum of stroke patients were compared to stroke mimics with matched cardio- and cerebrovascular risk factors, with corroboration of results in a pre-clinical model. An unbiased miRNA microarray was performed in stroke vs. stroke mimic patients (n = 39). Results were validated (n = 173 patients) by real-time quantitative polymerase chain reaction. miRNA expression was quantified in total serum/EV (n = 5-7) of naïve adult spontaneously hypertensive stroke-prone rats (SHRSP), their normotensive reference strain (Wistar Kyoto, WKY) and in circulating EV (n = 3), peri-infarct brain (n = 6), or EV derived from this region (n = 3) in SHRSP following transient middle cerebral artery occlusion (tMCAO)...
January 7, 2019: Translational Stroke Research
J W Rutten, E B van den Akker, S A J Lesnik Oberstein
No abstract text is available yet for this article.
December 18, 2018: Translational Stroke Research
Ashfaq Shuaib, Naveed Akhtar, Saadat Kamran, Richard Camicioli
Cerebral microbleeds (CMBs) are very frequent diagnoses with MRI imaging in the elderly or in patients with cerebral infarction, intracranial hemorrhage (ICH), and dementia. The mechanisms for CMBs are not fully understood but may be secondary to injury to the vascular wall from long-standing hypertension or amyloid deposition in the tissue. The presence of CMB increases the risk for stroke, dementia, and death. The increasing number of CMBs is also associated with a higher risk of hemorrhagic complications with the long-term use of anticoagulants in atrial fibrillation and in patients requiring thrombolysis for acute stroke...
December 15, 2018: Translational Stroke Research
Roger Simon, Robert Meller, Tao Yang, Andrea Pearson, Glenn Wilson
We hypothesize that enhancing mitochondrial base excision repair (BER) capability in brain will reduce reperfusion-associated ischemic brain injury. Post-stroke reperfusion was modeled in mice via transient filament occlusion of the middle cerebral artery (60 min) (transient MCAO). Administration of a TAT-modified form of a DNA glycosylase (EndoIII) following reperfusion of the brain reduced resultant brain infarct volume. Protection was dose-dependent, BER enzyme specific, and regionally specific (more effective via the jugular vein)...
December 8, 2018: Translational Stroke Research
Wan Zhu, Daniel Saw, Miriam Weiss, Zhengda Sun, Meng Wei, Sonali Shaligram, Sen Wang, Hua Su
Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. The pathogenesis of bAVM has not been fully understood. Animal models are important tools for dissecting bAVM pathogenesis and testing new therapies. We have developed several mouse bAVM models using genetically modified mice. However, due to the body size, mouse bAVM models have some limitations. Recent studies identified somatic mutations in sporadic human bAVM. To develop a feasible tool to create sporadic bAVM in rodent and animals larger than rodent, we made tests using the CRISPR/Cas9 technique to induce somatic gene mutations in mouse brain in situ...
December 3, 2018: Translational Stroke Research
Graeme A Deuchar, Josie C van Kralingen, Lorraine M Work, Celestine Santosh, Keith W Muir, Chris McCabe, I Mhairi Macrae
In acute stroke patients, penumbral tissue is non-functioning but potentially salvageable within a time window of variable duration and represents target tissue for rescue. Reperfusion by thrombolysis and/or thrombectomy can rescue penumbra and improve stroke outcomes, but these treatments are currently available to a minority of patients. In addition to the utility of Glasgow Oxygen Level Dependent (GOLD) as an MRI contrast capable of detecting penumbra, its constituent perfluorocarbon (PFC) oxygen carrier, combined with normobaric hyperoxia, also represents a potential acute stroke treatment through improved oxygen delivery to penumbra...
November 30, 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
Ye Liu, Emma D Eaton, Taryn E Wills, Sarah K McCann, Ana Antonic, David W Howells
Low translational yield for stroke may reflect the focus of discovery science on rodents rather than humans. Just how little is known about human neuronal ischaemic responses is confirmed by systematic review and meta-analysis revealing that data for the most commonly used SH-SY5Y human cells comprises only 84 papers. Oxygen-glucose deprivation, H2 O2 , hypoxia, glucose-deprivation and glutamate excitotoxicity yielded - 58, - 61, - 29, - 45 and - 49% injury, respectively, with a dose-response relationship found only for H2 O2 injury (R2  = 29...
December 2018: 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...
December 2018: Translational Stroke Research
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