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Brain protection stroke

Yanier Nuñez-Figueredo, Jeney Ramírez-Sánchez, Gilberto L Pardo Andreu, Estael Ochoa-Rodríguez, Yamila Verdecia-Reyes, Diogo O Souza
Ischemic stroke is a major cause of death and disability worldwide. Thrombolysis by tissue plasminogen activator is the only pharmacological treatment approved for clinical practice, but has a narrow therapeutic window and poor efficacy when the cell death cascade is activated. Numerous drugs that are thought to protect neurons against injury have previously failed in human trials despite showing efficacy in experimental models of stroke. Herein, we reviewed the main pre-clinical results of the neuroprotective effects of JM-20, a new hybrid molecule, against brain ischemia...
February 12, 2018: Pharmacological Reports: PR
Liang Shu, Ben Chen, Bin Chen, Hai Xu, Guoxiang Wang, Yian Huang, Yingya Zhao, Hui Gong, Min Jiang, Lidian Chen, Xu Liu, Yun Wang
Ischemic stroke not only induces neuron death in the infarct area but also structural and functional damage of the surviving neurons in the surrounding peri-infarct area. In the present study, we first identified cofilin rod, a pathological rod-like aggregation, formed in neurons of in vivo ischemic stroke animal model and induced neuronal impairment. Cofilin rods formed only on the ipsilateral side of the middle cerebral artery occlusion and reperfusion (MCAO-R) rat brain and showed the highest density in peri-infarct area...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Qunqun Bao, Ping Hu, Yingying Xu, Tiansheng Cheng, Chenyang Wei, Limin Pan, Jianlin Shi
Cerebral vasculature and neuronal networks will be largely destroyed due to the oxidative damages by over-produced reactive oxygen species (ROS) during stroke, accompanied by the symptoms of ischemic injury and blood-brain barrier (BBB) disruption. Ceria nanoparticles, acting as an effective and recyclable ROS scavenger, have been showing high effectiveness in neuroprotection. However, the brain access of nanoparticles can only be achieved by targeting the damaged area of BBB, leading to the disrupted BBB unprotected and turbulence of microenvironment in brain...
June 22, 2018: ACS Nano
Jianping Wang, Di Zhang, Xiaojie Fu, Lie Yu, Zhengfang Lu, Yufeng Gao, Xianliang Liu, Jiang Man, Sijia Li, Nan Li, Xuemei Chen, Michael Hong, Qingwu Yang, Jian Wang
BACKGROUND: At low levels, carbon monoxide (CO) has been shown to have beneficial effects on multiple organs and tissues through its potential anti-inflammatory, anti-apoptotic, and anti-proliferative properties. However, the effect of CO-releasing molecule (CORM)-3, a water-soluble CORM, on ischemic stroke and its mechanism of action are still unclear. METHODS: We investigated the role of CORM-3 in the mouse model of transient middle cerebral artery occlusion (tMCAO)...
June 21, 2018: Journal of Neuroinflammation
Wei-Ting Lee, Shih-Huang Tai, Yu-Wen Lin, Tian-Shung Wu, E-Jian Lee
3‑(5‑hydroxymethyl‑2‑furyl)‑1‑benzyl‑indazole (YC‑1) is understood to protect against ischemic stroke, but the molecular basis for its neuroprotection remains to be fully characterized. The present study investigated the influence of YC‑1 on inflammatory responses following experimental stroke. Previous studies indicated that nuclear factor (NF)‑κB‑driven signals serve a pivotal role in mediating inflammatory responses following stroke. Ischemic stroke results in activation of NF‑κB to induce gene expression of factors including inducible nitric oxide synthase, interleukin (IL)‑1β, IL‑6 and matrix metalloproteinases (MMPs)...
June 15, 2018: Molecular Medicine Reports
Hye-Won Ryu, Wonbong Lim, Danbi Jo, Subin Kim, Jong Tae Park, Jung-Joon Min, Hoon Hyun, Hyung-Seok Kim
Background: Evans blue dye (EBD) is the most common indicator to analyze the extent of blood-brain barrier (BBB) breakdown in several neurological disease models. However, the high-dose of EBD (51.9 mg/kg) is usually required for visualization of blue color by the human eye that brings potential safety issues. Methods: To solve this problem, low-dose of EBD was applied for the near-infrared (NIR) fluorescence-assisted quantitation of BBB breakdown in photothrombotic stoke model. Animals were allocated to seven dose groups ranging from 1...
2018: International Journal of Medical Sciences
Gerónimo Fernández, Ana Moraga, María I Cuartero, Alicia García-Culebras, Carolina Peña-Martínez, Jesús M Pradillo, Macarena Hernández-Jiménez, Silvia Sacristán, M Irene Ayuso, Rafael Gonzalo-Gobernado, David Fernández-López, M Elena Martín, María A Moro, Victor M González, Ignacio Lizasoain
Since Toll-like receptor 4 (TLR4) mediates brain damage after stroke, development of TLR4 antagonists is a promising therapeutic strategy for this disease. Our aim was to generate TLR4-blocking DNA aptamers to be used for stroke treatment. From a random oligonucleotide pool, we identified two aptamers (ApTLR#1R, ApTLR#4F) with high affinity for human TLR4 by systematic evolution of ligands by exponential enrichment (SELEX). Optimized truncated forms (ApTLR#1RT, ApTLR#4FT) were obtained. Our data demonstrate specific binding of both aptamers to human TLR4 as well as a TLR4 antagonistic effect...
June 15, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Qianping Luo, Yong Fan, Lili Lin, Jingjing Wei, Zuanfang Li, Yongkun Li, Susumu Nakae, Wei Lin, Qi Chen
Interleukin-33 (IL-33), a novel member of the IL-1 family, expressed in many tissue and cell types, and is involved in inflammation and immune functions. Previous studies suggest that IL-33 may play a role in ischemic stroke. We tried to investigate the role of IL-33 in cerebral ischemia-reperfusion-induced injury and its underlying mechanism. Our data indicated that IL-33 deficiency exacerbated the neurological dysfunction caused by cerebral ischemia-reperfusion injury in mice and led to the formation of larger cerebral infarct volume as shown by 2,3,5-triphenyltetrazolium chloride (TTC) staining and magnetic resonance imaging...
June 12, 2018: Neuroscience
M Samsonia, M Kandelaki, N Baratashvili
Cerebrovascular diseases of ischemic origin still remain the leading cause of death and disability of the population. In acute cerebral discirculation conditions, anaerobic glycolysis is activated, ATP formation rate decreases, the ion pumps work is disrupted and superoxide radicals are formed. Eventually, ionic asymmetry leads to the cytotoxic and vasogenic brain edema. Therefore, it is extremely important to induce simultaneous (complex) effect of medications on the key mechanisms of neuronal damage in process of survival of brain cells during acute ischemic stroke...
May 2018: Georgian Medical News
Yuanyuan Ran, Zongjian Liu, Shuo Huang, Jiamei Shen, Fengwu Li, Wenxiu Zhang, Chen Chen, Xiaokun Geng, Zhili Ji, Huishan Du, Xiaoming Hu
Splenectomy before or immediately after stroke provides early brain protection. This study aims to explore the effect of splenectomy on long-term neurological recovery after stroke, which is currently lacking in the field. Adult male rats were randomized into splenectomy or sham groups and then subjected to 90 min of middle cerebral artery occlusion (MCAO). Spleen was removed right upon reperfusion or 3d after MCAO. Infarct volume, neurological functions, and peripheral immune cell populations were assessed up to 28d after stroke...
June 2018: Aging and Disease
Xiangrong Liu, Shaohong Wen, Shunying Zhao, Feng Yan, Shangfeng Zhao, Di Wu, Xunming Ji
Mild therapeutic hypothermia, a robust neuroprotectant, reduces neuronal apoptosis, but the precise mechanism is not well understood. Our previous study showed that a novel inhibitor of an apoptosis-stimulating protein of p53 (iASPP) might be involved in neuronal death after stroke. The aim of this study was to confirm the role of iASPP after stroke treated with mild therapeutic hypothermia. To address this, we mimicked ischemia/reperfusion injury in vitro by using oxygen-glucose deprivation/reperfusion (OGD/R) in primary rat neurons...
June 2018: Aging and Disease
Gyeong Bok Jung, Sung Wook Kang, Gi-Ja Lee, Dohyun Kim
Cerebral ischemic stroke is one of the most common neurodegenerative conditions characterized by cerebral infarction, death of the brain tissue, and loss of brain function. Cerebral ischemia-reperfusion injury is the tissue damage caused when blood supply begins to the tissue after a period of ischemia or poor oxygen supply. In this study, we preliminarily investigated the biochemical changes in the brain hippocampal area, CA1, resulting from ischemia reperfusion and neuronal nitric oxide synthase (nNOS) inhibitor treatment in rats using Raman spectroscopy...
January 1, 2018: Applied Spectroscopy
Ariel Diaz, Paola Merino, Luis G Manrique, Lihong Cheng, Manuel Yepes
Cerebral ischemia has a harmful effect on the synapse associated with neurological impairment. The "tripartite synapse" is assembled by the pre- and postsynaptic terminals, embraced by astrocytic elongations known as peripheral astrocytic processes (PAPs). Ischemic stroke induces the detachment of PAPs from the synapse, leading to synaptic dysfunction and neuronal death. Ezrin is a membrane-associated protein, required for the formation of PAPs, that links the cell surface to the actin cytoskeleton...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Meng Chen, Wenyan Zou, Miaomiao Chen, Liang Cao, Jianhua Ding, Wei Xiao, Gang Hu
Ginkgolide K (GK) is a new compound extracted from the leaves of Ginkgo biloba, which has been recognized to exert anti-oxidative stress and neuroprotective effect on ischemic stroke. While whether it plays an enhanced effect on angiogenesis during ischemic stroke remains unknown. The aim of this study was to investigate the effect of ginkgolide K on promoting angiogenesis as well as the protective mechanism after cerebral ischemia-reperfusion. Using the transient middle cerebral artery occlusion (tMCAO) mouse model, we found that GK (3...
June 8, 2018: European Journal of Pharmacology
R Stolmeijer, H R Bouma, J G Zijlstra, A M Drost-de Klerck, J C Ter Maaten, J J M Ligtenberg
Introduction: Despite widespread and liberal use of oxygen supplementation, guidelines about rational use of oxygen are scarce. Recent data demonstrates that current protocols lead to hyperoxemia in the majority of the patients and most health care professionals are not aware of the negative effects of hyperoxemia. Method: To investigate the effects of hyperoxemia in acutely ill patients on clinically relevant outcomes, such as neurological and functional status as well as mortality, we performed a literature review using Medline (PubMed) and Embase...
2018: BioMed Research International
Yasin Asadi, Fazel Gorjipour, Sedigheh Behrouzifar, Abedin Vakili
Evidence has shown therapeutic potential of irisin in cerebral stroke. The present study aimed to assess the effects of recombinant irisin on the infarct size, neurological outcomes, blood-brain barrier (BBB) permeability, apoptosis and brain-derived neurotrophic factor (BDNF) expression in a mouse model of stroke. Transient focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) for 45 min and followed reperfusion for 23 h in mice. Recombinant irisin was administrated at doses of 0...
June 7, 2018: Neurochemical Research
Rui Zhan, Mingming Zhao, Ting Zhou, Yue Chen, Weiwei Yu, Lei Zhao, Tao Zhang, Hecheng Wang, Huan Yang, Yinglan Jin, Qihua He, Xiaoda Yang, Xiangyang Guo, Belinda Willard, Bing Pan, Yining Huang, Yingyu Chen, Dehua Chui, Lemin Zheng
Atherosclerosis was considered to induce many vascular-related complications, such as acute myocardial infarction and stroke. Abnormal lipid metabolism and its peroxidation inducing blood-brain barrier (BBB) leakage were associated with the pre-clinical stage of stroke. Dapsone (DDS), an anti-inflammation and anti-oxidation drug, has been found to have protective effects on vascular. However, whether DDS has a protective role on brain microvessels during lipid oxidation had yet to be elucidated. We investigated brain microvascular integrity in a high-fat diet (HFD) mouse model...
June 7, 2018: Cell Death & Disease
Shuhui Dai, Ya Hua, Richard F Keep, Nemanja Novakovic, Zhou Fei, Guohua Xi
Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocycline reduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats...
June 4, 2018: Neurobiology of Disease
Ghazal Aarabi, Götz Thomalla, Guido Heydecke, Udo Seedorf
Chronic oral infections (gingivitis/periodontitis) have been associated with age-related diseases such as diabetes, coronary heart disease and acute ischemic stroke. In addition, imaging surrogates of cerebrovascular ischemia beyond acute ischemic stroke (i.e. silent strokes and brain white matter hyperintensities) may also be associated with chronic oral infections. The pathology underlying lacunar strokes and brain white matter hyperintensities relates to small vessel disease in the brain. In this review, we highlight recent progress in exploring potential associations of oral infections with cerebral small vessel disease and its surrogates (silent strokes, white matter hyperintensities) and clinical sequelae (i...
June 7, 2018: Oral Diseases
Zhifeng Zhong, Jing Han, Jizhou Zhang, Qing Xiao, Juan Hu, Lidian Chen
The primary objective of this review article was to summarize comprehensive information related to the neuropharmacological activity, mechanisms of action, toxicity, and safety of salidroside in medicine. A number of studies have revealed that salidroside exhibits neuroprotective activities, including anti-Alzheimer's disease, anti-Parkinson's disease, anti-Huntington's disease, anti-stroke, anti-depressive effects, and anti-traumatic brain injury; it is also useful for improving cognitive function, treating addiction, and preventing epilepsy...
2018: Drug Design, Development and Therapy
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