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https://www.readbyqxmd.com/read/29789393/long-term-outcomes-in-patients-aged-%C3%A2-70-years-with-intravenous-glyburide-from-the-phase-ii-games-rp-study-of-large-hemispheric-infarction-an-exploratory-analysis
#1
Kevin N Sheth, Nils H Petersen, Ken Cheung, Jordan J Elm, Holly E Hinson, Bradley J Molyneaux, Lauren A Beslow, Gordon K Sze, J Marc Simard, W Taylor Kimberly
BACKGROUND AND PURPOSE: We aimed to determine whether subjects aged ≤70 years who were treated with intravenous glyburide (RP-1127; BIIB093; glibenclamide) would have better long-term outcomes than those who received placebo. METHODS: GAMES-RP (Glyburide Advantage in Malignant Edema and Stroke-Remedy Pharmaceuticals) was a prospective, double-blind, randomized, placebo-controlled phase 2 clinical trial. Eighty-six participants, aged 18 to 80 years, who presented to 18 centers with large hemispheric infarction (baseline diffusion-weighted imaging volumes, 82-300 cm3 ) randomized within 10 hours of symptom onset were enrolled...
May 22, 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29776835/the-combination-of-mannitol-and-temozolomide-increases-the-effectiveness-of-stem-cell-treatment-in-a-chronic-stroke-model
#2
Chunggab Choi, Hye Min Kim, Jeeheun Shon, Jiae Park, Hyeong-Taek Kim, Suk Ho Kang, Seung-Hun Oh, Nam Keun Kim, Ok Joon Kim
BACKGROUND: The blood-brain barrier (BBB) presents a significant challenge to the therapeutic efficacy of stem cells in chronic stroke. Various methods have been developed to increase BBB permeability, but these are associated with adverse effects and are, therefore, not clinically applicable. We recently identified that combination drug treatment of mannitol and temozolomide improved BBB permeability in vitro. Here, we investigated whether this combination could increase the effectiveness of stem cell treatment in an animal model of chronic ischemic stroke...
May 15, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29775963/brain-ischemic-preconditioning-protects-against-ischemic-injury-and-preserves-the-blood-brain-barrier-via-oxidative-signaling-and-nrf2-activation
#3
Tuo Yang, Yang Sun, Leilei Mao, Meijuan Zhang, Qianqian Li, Lili Zhang, Yejie Shi, Rehana K Leak, Jun Chen, Feng Zhang
Brain ischemic preconditioning (IPC) with mild ischemic episodes is well known to protect the brain against subsequent ischemic challenges. However, the underlying mechanisms are poorly understood. Here we demonstrate the critical role of the master redox transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), in IPC-mediated neuroprotection and blood-brain barrier (BBB) preservation. We report that IPC causes generation of endogenous lipid electrophiles, including 4-hydroxy-2-nonenal (4-HNE), which release Nrf2 from inhibition by Keap1 (via Keap1-C288) and inhibition by glycogen synthase kinase 3β (via GSK3β-C199)...
May 6, 2018: Redox Biology
https://www.readbyqxmd.com/read/29770166/free-radical-damage-in-ischemia-reperfusion-injury-an-obstacle-in-acute-ischemic-stroke-after-revascularization-therapy
#4
REVIEW
Ming-Shuo Sun, Hang Jin, Xin Sun, Shuo Huang, Fu-Liang Zhang, Zhen-Ni Guo, Yi Yang
Acute ischemic stroke is a common cause of morbidity and mortality worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. However, ischemia-reperfusion injury after revascularization therapy can result in worsening outcomes. Among all possible pathological mechanisms of ischemia-reperfusion injury, free radical damage (mainly oxidative/nitrosative stress injury) has been found to play a key role in the process...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29770118/neuroinflammation-as-a-target-for-intervention-in-subarachnoid-hemorrhage
#5
REVIEW
Airton Leonardo de Oliveira Manoel, R Loch Macdonald
Aneurysmal subarachnoid hemorrhage (SAH) is a sub-type of hemorrhagic stroke associated with the highest rates of mortality and long-term neurological disabilities. Despite the improvement in the management of SAH patients and the reduction in case fatality in the last decades, disability and mortality remain high in this population. Brain injury can occur immediately and in the first days after SAH. This early brain injury can be due to physical effects on the brain such as increased intracranial pressure, herniations, intracerebral, intraventricular hemorrhage, and hydrocephalus...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29760276/early-blood-brain-barrier-disruption-in-ischemic-stroke-initiates-multifocally-around-capillaries-venules
#6
Angelika Hoffmann, Tassilo Dege, Reiner Kunze, Anne-Sophie Ernst, Holger Lorenz, Laura-Inés Böhler, Thomas Korff, Hugo H Marti, Sabine Heiland, Martin Bendszus, Xavier Helluy, Mirko Pham
BACKGROUND AND PURPOSE: Detection and localization of the early phase of blood-brain barrier disruption (BBBD) in vivo during cerebral ischemia/reperfusion injury remain a major challenge but may be a relevant outcome parameter in stroke. METHODS: We studied early BBBD in mice after transient middle cerebral artery occlusion by multimodal, high-field (9.4T) in vivo magnetic resonance imaging, including the contrast agent gadofluorineM as an albumin-binding tracer...
May 14, 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29744447/in-vivo-evaluation-of-urokinase-loaded-hollow-nanogels-for-sonothrombolysis-on-suture-embolization-induced-acute-ischemic-stroke-rat-model
#7
Yuming Teng, Haiqiang Jin, Ding Nan, Mengnan Li, Chenghe Fan, Yuanyuan Liu, Pu Lv, Wei Cui, Yongan Sun, Hongjun Hao, Xiaozhong Qu, Zhenzhong Yang, Yining Huang
The urokinase-type plasminogen activator (uPA) loaded hollow nanogels (nUK) were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly (ethylene oxide). The resultant formulation is sensitive to diagnostic ultrasound (US) of 2 MHz. Herein, we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery (MCA). Via intravenous (i.v.) administration, the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation, leading to enhanced thrombolysis efficiency of the nUK, evidenced from smaller infarct volume and better clinical scores when compared to the i...
March 2018: Bioactive Materials
https://www.readbyqxmd.com/read/29743683/rivaroxaban-does-not-influence-hemorrhagic-transformation-in-a-diabetes-ischemic-stroke-and-endovascular-thrombectomy-model
#8
Feng-Di Liu, Rong Zhao, Xiao-Yan Feng, Yan-Hui Shi, Yi-Lan Wu, Xiao-Lei Shen, Ge-Fei Li, Yi-Sheng Liu, Ying Zhao, Xin-Wei He, Jia-Wen Yin, Mei-Ting Zhuang, Bing-Qiao Zhao, Jian-Ren Liu
Managing endovascular thrombectomy (ET) in diabetic ischemic stroke (IS) with novel anticoagulants is challenging due to putative risk of intracerebral hemorrhage. The study evaluates increased hemorrhagic transformation (HT) risk in Rivaroxaban-treated diabetic rats post ET. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 60 mg/kg streptozotocin. After 4-weeks, rats were pretreated orally with 30 mg/kg Rivaroxaban/saline; prothrombin time was monitored. IS and ET was induced after 1 h, by thread-induced transient middle cerebral artery occlusion (tMCAO) that mimicked mechanical ET for proximal MCA occlusion at 60 min...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739261/exacerbated-brain-edema-in-a-rat-streptozotocin-model-of-hyperglycemic-ischemic-stroke-evidence-for-involvement-of-blood-brain-barrier-na-k-cl-cotransport-and-na-h-exchange
#9
Natalie Y Yuen, Olga V Chechneva, Yi-Je Chen, Yi-Chen Tsai, Logan K Little, James Dang, Daniel J Tancredi, Jacob Conston, Steven E Anderson, Martha E O'Donnell
Cerebral edema is exacerbated in diabetic ischemic stroke through poorly understood mechanisms. We showed previously that blood-brain barrier (BBB) Na-K-Cl cotransport (NKCC) and Na/H exchange (NHE) are major contributors to edema formation in normoglycemic ischemic stroke. Here, we investigated whether hyperglycemia-exacerbated edema involves changes in BBB NKCC and NHE expression and/or activity and whether inhibition of NKCC or NHE effectively reduces edema and injury in a type I diabetic model of hyperglycemic stroke...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29734653/the-janus-face-of-vegf-in-stroke
#10
REVIEW
Samuel J Geiseler, Cecilie Morland
The family of vascular endothelial growth factors (VEGFs) are known for their regulation of vascularization. In the brain, VEGFs are important regulators of angiogenesis, neuroprotection and neurogenesis. Dysregulation of VEGFs is involved in a large number of neurodegenerative diseases and acute neurological insults, including stroke. Stroke is the main cause of acquired disabilities, and normally results from an occlusion of a cerebral artery or a hemorrhage, both leading to focal ischemia. Neurons in the ischemic core rapidly undergo necrosis...
May 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29729895/implications-of-polymorphonuclear-neutrophils-for-ischemic-stroke-and-intracerebral-hemorrhage-predictive-value-pathophysiological-consequences-and-utility-as-therapeutic-target
#11
REVIEW
Dirk M Hermann, Christoph Kleinschnitz, Matthias Gunzer
Polymorphonuclear neutrophil granulocytes (PMN) orchestrate the removal of cell debris in ischemic stroke and intracerebral hemorrhage. In both pathologies, high neutrophil to lymphocyte ratios in peripheral blood are predictive of poor outcome in human stroke patients. Following earlier studies indicating that the cerebral microvasculature forms an efficient barrier that impedes neutrophil brain entry, intravital microscopy and immunohistochemistry in the meantime unequivocally revealed the accumulation of PMN in the ischemic and hemorrhagic brain parenchyma...
April 24, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29728011/the-protective-roles-of-l-borneolum-d-borneolum-and-synthetic-borneol-in-cerebral-ischaemia-via-modulation-of-the-neurovascular-unit
#12
Taiwei Dong, Nian Chen, Xiao Ma, Jian Wang, Jing Wen, Qian Xie, Rong Ma
OBJECTIVE: Borneol has been used to treat stroke in China since ancient times. In our previous research, we demonstrated the effect of borneol on cerebral ischaemia injury via meta-analysis. The neurovascular unit (NVU) is the structural basis of the preservation of the brain microenvironment and is believed to be a promising target in treating stroke. In this research, we explored the roles of three kinds of borneol, namely, L-borneolum (B1), D-borneolum (B2) and synthetic borneol (B3), in the NVU with permanent middle cerebral artery occluded (pMCAO) rats...
June 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29726891/understanding-the-role-of-the-perivascular-space-in-cerebral-small-vessel-disease
#13
Rosalind Brown, Helene Benveniste, Sandra E Black, Serge Charpak, Martin Dichgans, Anne Joutel, Maiken Nedergaard, Kenneth J Smith, Berislav V Zlokovic, Joanna M Wardlaw
Small vessel diseases are a group of disorders that result from pathological alteration of the small blood vessels in the brain, including the small arteries, capillaries and veins. Of the 35-36 million people that are estimated to suffer from dementia worldwide, up to 65% have an SVD component. Furthermore, SVD causes 20-25% of strokes, worsens outcome after stroke and is a leading cause of disability, cognitive impairment and poor mobility. Yet the underlying cause(s) of SVD are not fully understood.Magnetic resonance imaging (MRI) has confirmed enlarged perivascular spaces (PVS) as a hallmark feature of SVD...
May 2, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29724893/role-of-autophagy-in-endothelial-damage-and-blood-brain-barrier-disruption-in-ischemic-stroke
#14
REVIEW
Kyeong-A Kim, Donggeun Shin, Jeong-Hyeon Kim, Young-Jun Shin, G K Rajanikant, Arshad Majid, Seung-Hoon Baek, Ok-Nam Bae
No abstract text is available yet for this article.
May 3, 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29724240/mesenchymal-stem-cells-attenuate-blood-brain-barrier-leakage-after-cerebral-ischemia-in-mice
#15
Zhuo Cheng, Liping Wang, Meijie Qu, Huaibin Liang, Wanlu Li, Yongfang Li, Lidong Deng, Zhijun Zhang, Guo-Yuan Yang
BACKGROUND: Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1)...
May 3, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29722298/acupuncture-and-neuroregeneration-in-ischemic-stroke
#16
REVIEW
Qwang-Yuen Chang, Yi-Wen Lin, Ching-Liang Hsieh
Acupuncture is potentially beneficial for post-stroke rehabilitation and is considered a promising preventive strategy for stroke. Electroacupuncture pretreatment or treatment after ischemic stroke by using appropriate electroacupuncture parameters generates neuroprotective and neuroregenerative effects that increase cerebral blood flow, regulate oxidative stress, attenuate glutamate excitotoxicity, maintain blood-brain barrier integrity, inhibit apoptosis, increase growth factor production, and induce cerebral ischemic tolerance...
April 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29708005/microrna-based-therapeutics-in-central-nervous-system-injuries
#17
Ping Sun, Da Zhi Liu, Glen C Jickling, Frank R Sharp, Ke-Jie Yin
Central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI) and spinal cord injury (SCI), are important causes of death and long-term disability worldwide. MicroRNA (miRNA), small non-coding RNA molecules that negatively regulate gene expression, can serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. MiRNA-based therapeutics include miRNA mimics and inhibitors (antagomiRs) to respectively decrease and increase the expression of target genes...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29705606/neuroprotective-effects-of-protein-tyrosine-phosphatase-1b-inhibitor-on-cerebral-ischemia-reperfusion-in-mice
#18
Meiling Sun, Hisanao Izumi, Yasuharu Shinoda, Kohji Fukunaga
Akt (Protein kinase B, PKB), a serine/threonine kinase, plays a critical role in cell development, growth, and survival. Akt phosphorylation mediates a neuroprotective effect against ischemic injury. Recently, a protein-tyrosine phosphatase-1B (PTP1B) inhibitor (KY-226) was developed to elicit anti-diabetic and anti-obesity effects via enhancement of insulin signaling. Previously, we reported that the nonselective PTP1B inhibitor, sodium orthovanadate, rescued neurons from delayed neuronal death during brain ischemia...
April 26, 2018: Brain Research
https://www.readbyqxmd.com/read/29681883/compromised-blood-brain-barrier-integrity-is-associated-with-total-magnetic-resonance-imaging-burden-of-cerebral-small-vessel-disease
#19
Yue Li, Man Li, Long Zuo, Qinglei Shi, Wei Qin, Lei Yang, Tao Jiang, Wenli Hu
Objective: Several studies have demonstrated that compromised blood-brain barrier (BBB) integrity may play a pivotal role in the pathogenesis of individual cerebral small vessel disease (cSVD) markers, but the association between BBB permeability and total magnetic resonance imaging (MRI) cSVD burden remains unclear. This study aimed to investigate the relationship between BBB permeability and total MRI cSVD burden. Methods: Consecutive participants without symptomatic stroke history presented for physical examination were enrolled in this cross-sectional study...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29681849/danhong-injection-combined-with-t-pa-improves-thrombolytic-therapy-in-focal-embolic-stroke
#20
Min Li, Jing Zhou, Weifeng Jin, Xiaohong Li, Yuyan Zhang
Background: Hemorrhagic transformation, neurotoxicity, short treatment time windows, and other defects are considered as the major limitations for the thrombolytic therapy. This study is devoted to figure out whether Danhong injection (DHI) combined with tissue-plasminogen activator (t-PA) could extend the treatment time windows and ameliorate brain injury, hemorrhagic complication and BBB disruption after focal embolic stroke. Methods: In vitro , the combined concentrations of DHI and t-PA were added to wells reacted with plasminogen and D-Val-Leu-Lys-AMC...
2018: Frontiers in Pharmacology
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