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Stroke reperfusion injury

Frank W Blixt, Kristian Agmund Haanes, Lena Ohlsson, Karin Dreisig Sörensen, Vadim Fedulov, Karin Warfvinge, Lars Edvinsson
Retinal ischemia remains a major cause of blindness in the world with few acute treatments available. Recent emphasis on retinal vasculature and the ophthalmic artery's vascular properties after ischemia has shown an increase in vasoconstrictive functionality, as previously observed in cerebral arteries following stroke. Specifically, endothelin-1 (ET-1) receptor-mediated vasoconstriction regulated by the MEK/ERK1/2 pathway. In this study, the ophthalmic artery of rats was occluded for 2 h with the middle cerebral artery occlusion model...
November 12, 2018: Experimental Eye Research
Rebecca J Wilson, Joshua Chadwick Drake, Di Cui, Matthew Lonergan Ritger, Yuntian Guan, Jarrod A Call, Mei Zhang, Lucia Marie Leitner, Axel Gödecke, Zhen Yan
Ischemia-reperfusion (IR) due to temporary restriction of blood flow causes tissue/organ damages under various disease conditions, including stroke, myocardial infarction, trauma and orthopedic surgery. In the limbs, IR injury to motor nerves and muscle fibers causes reduced mobility and quality of life. Endurance exercise training has been shown to increase tissue resistance to numerous pathological insults. To elucidate the impact of endurance exercise training on IR injury in skeletal muscle, sedentary and exercise-trained mice (5 weeks of voluntary running) were subjected to ischemia by unilateral application of a rubber band tourniquet above the femur for 1 hour followed by reperfusion...
November 15, 2018: Journal of Applied Physiology
Hang Yu, Xiaozhi Wang, Fuxin Kang, Zhile Chen, Yunxia Meng, Mingming Dai
The overall incidence rate of stroke is increasing worldwide. Inflammatory damage following a stroke is a leading cause for the poor prognosis and high disability rate observed in stroke patients. Microglia are considered to be the main causative agents of inflammatory injury following cerebral infarction, as they secrete various inflammatory cytokines and cytotoxic factors. The aim of the present study was to identify novel methods for attenuating inflammatory injury and improving the prognosis of stroke patients...
November 5, 2018: International Journal of Molecular Medicine
Yuan-Jian Song, Chun-Xiao Dai, Man Li, Miao-Miao Cui, Xin Ding, Xiao-Fang Zhao, Cai-Lin Wang, Zhen-Ling Li, Meng-Yuan Guo, Xiang-Ru Wen, Da-Shi Qi, Yu-Lan Wang
Heme oxygenase (HO-1), which may be induced by Cobaltic protoporphyrin IX chloride (CoPPIX) or Rosiglitazone (Ros), is a neuroprotective agent that effectively reduces ischemic stroke. Previous studies have shown that the neuroprotective mechanisms of HO-1 are related to JNK signaling. The expression of HO-1 protects cells from death through the JNK signaling pathway. This study aimed to ascertain whether the neuroprotective effect of HO-1 depends on the assembly of the MLK3-MKK7-JNK3 signaling module scaffolded by JIP1 and further influences the JNK signal transmission through HO-1...
November 6, 2018: Behavioural Brain Research
Guangchao Zhao, Lujia Yang, Shiquan Wang, Min Cai, Sisi Sun, Hailong Dong, Lize Xiong
It is known that preconditional treatment with volatile anesthetics can induce tolerance of the brain to stroke. A previous study demonstrated that the involvement of TREK-1, a two-pore domain K+ channel, in sevoflurane preconditioning-induced neuroprotection against focal cerebral ischemia in rats. The present study testified whether TREK-2, another anesthetics-target K+ channels, is also associated with volatile anesthetics-induced neuroprotection, and further explored its potential mechanism. METHODS: Rats preconditioned with isoflurane were subjected to 1...
November 9, 2018: Rejuvenation Research
Saibin Wang, Qian Ye, Junwei Tu
Stroke-associated ocular disorders are vision-threatening. This study was designed to evaluate in vivo retinal injury induced by transient global cerebral ischemia/reperfusion (I/R). A stroke-induced retinal injury model in Wistar rats was established by electrocoagulation of bilateral vertebral arteries, combined with transient ligation of the bilateral common carotid arteries. Rats were randomly divided into groups based on the time post cerebral perfusion (3 h, 24 h, 48 h, 72 h, and 7 days). Retinal injury was evaluated by histological analysis, examination of eye fundus, and TUNEL staining...
November 9, 2018: Histology and Histopathology
Diogo C Haussen, Ivan M Ferreira, Clara Barreira, Jonathan A Grossberg, Francesco Diana, Simone Peschillo, Raul G Nogueira
Introduction: Symptomatic intracranial hemorrhage represents one of the most feared complications of endovascular reperfusion. We aim to describe a series of patients that experienced immediate reperfusion injury with active intraprocedural extravasation within the territory of the deep penetrating arteries and provide real-time correlation with CT "spot sign." Methods: This was a retrospective analysis of patients that suffered reperfusion injury with active arterial extravasation during endovascular stroke treatment in two tertiary care centers...
October 2018: Interventional Neurology
Yingzhu Chen, Liangzhu Wang, Lingling Zhang, Beilei Chen, Liu Yang, Xiaobo Li, Yuping Li, Hailong Yu
Connexin 43 (Cx43) widely exists in all components of the neurovascular unit (NVU) and is a constituent of gap junctions and hemichannels. In physiological states, gap junctions are open for regular intercellular communication, and the hemichannels present low open probability in astrocytes. After cerebral ischemia, a large number of hemichannels are unusually opened, leading to cell swelling and even death. Most known hemichannel blockers also inhibit gap junctions and sequentially obstruct normal electrical cell-cell communication...
2018: Frontiers in Cellular Neuroscience
Shaonan Hu, Yali Wu, Bo Zhao, Haiyan Hu, Baochen Zhu, Zongxi Sun, Pengyue Li, Shouying Du
Oxidative stress plays a critical role in cerebral ischemia/reperfusion (I/R)-induced blood-brain barrier (BBB) disruption. Panax notoginseng saponins (PNS) possess efficient antioxidant activity and have been used in the treatment of cerebral ischemic stroke in China. In this study, we determined the protective effects of PNS on BBB integrity and investigated the underlying mechanism in cerebral microvascular endothelial cells (bEnd.3) exposed to oxygen-glucose deprivation/reperfusion (OGD/R). MTT and LDH release assays revealed that PNS mitigated the OGD/R-induced cell injury in a dose-dependent manner...
October 26, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Chikako Nito, Kota Sowa, Masataka Nakajima, Yuki Sakamoto, Satoshi Suda, Yasuhiro Nishiyama, Aki Nakamura-Takahashi, Yuko Nitahara-Kasahara, Masayuki Ueda, Takashi Okada, Kazumi Kimura
AIMS: Numerous experimental studies have shown that cellular therapy, including human dental pulp stem cells (DPSCs), is an attractive strategy for ischemic brain injury. Herein, we examined the effects of intravenous DPSC administration after transient middle cerebral artery occlusion in rats. METHODS: Male Sprague-Dawley rats received a transient 90 min middle cerebral artery occlusion. DPSCs (1 × 106 cells) or vehicle were administered via the femoral vein at 0 h or 3 h after ischemia-reperfusion...
September 27, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Leena Rastogi, Madan M Godbole, Rohit A Sinha, Sunil Pradhan
Hypothyroidism has been associated with better recovery from cerebral ischemia-reperfusion (IR) injury in humans. However, any therapeutic advantage of inducing hypothyroidism for mitigating IR injury without invoking the adverse effect of whole body hypothyroidism remains a challenge. We hypothesize that a deiodinase II (D2) inhibitor reverse triiodothyronine (rT3) may render brain specific hypometabolic state to ensue reduced damage during an acute phase of cerebral ischemia without affecting circulating thyroid hormone levels...
October 23, 2018: Biochemical and Biophysical Research Communications
Jianliang Geng, Yue Zhang, Sijia Li, Shuning Li, Jiankun Wang, Hong Wang, Jiye Aa, Guangji Wang
Ischemic tolerance renders the brain resistant to ischemia-reperfusion (I/R) injury as a result of the activation of endogenous adaptive responses triggered by various types of preconditioning. The complex underlying metabolic mechanisms responsible for the neuroprotection of cerebral ischemic preconditioning (IPC) remain elusive. Herein, gas chromatography-mass spectrometry (GC-MS) technique was applied to delineate the dynamic changes of brain metabolome in a rodent model of ischemic stroke (transient occlusion of the middle cerebral artery, tMCAO), alone or after pretreatment with nonlethal ischemic tolerance induction (transient occlusion of the bilateral common carotid arteries, tBCCAO)...
October 26, 2018: Journal of Proteome Research
Estelle Pruvost-Robieux, David Calvet, Wagih Ben Hassen, Guillaume Turc, Angela Marchi, Nicolas Mélé, Pierre Seners, Catherine Oppenheim, Jean-Claude Baron, Jean-Louis Mas, Martine Gavaret
Background: Stroke is a major cause of death and disability worldwide. The related burden is expected to further increase due to aging populations, calling for more efficient treatment. Ischemic stroke results from a focal reduction in cerebral blood flow due to the sudden occlusion of a brain artery. Ischemic brain injury results from a sequence of pathophysiological events that evolve over time and space. This cascade includes excitotoxicity and peri-infarct depolarizations (PIDs). Focal impairment of cerebral blood flow restricts the delivery of energetics substrates and impairs ionic gradients...
2018: Frontiers in Neurology
Baokai Dou, Wenjin Zhou, Shichun Li, Lixin Wang, Ximin Wu, Yiming Li, Huida Guan, Changhong Wang, Shiguo Zhu, Zunji Ke, Cheng Huang, Zhifei Wang
BACKGROUND/AIMS: Natural killer (NK) cells are among the first immune cells that respond to an ischemic insult in human brains. The infiltrated NK cells damage blood-brain barrier (BBB) and exacerbate brain infarction. Buyang Huanwu Decoction (BHD), a classic Chinese traditional herbal prescription, has long been used for the treatment of ischemic stroke. The present study investigated whether BHD can prevent brain infiltration of NK cells, attenuate BBB disruption and improve ischemic outcomes...
2018: Cellular Physiology and Biochemistry
Alexandre Meloux, Eve Rigal, Luc Rochette, Yves Cottin, Yannick Bejot, Catherine Vergely
Background and Purpose- For years, the relationship between cardiac and neurological ischemic events has been limited to overlapping pathophysiological mechanisms and common risk factors. However, acute stroke may induce dramatic changes in cardiovascular function. The aim of this study was to evaluate how prior cerebrovascular lesions affect myocardial function and signaling in vivo and ex vivo and how they influence cardiac vulnerability to ischemia-reperfusion injury. Methods- Cerebral embolization was performed in adult Wistar male rats through the injection of microspheres into the left or right internal carotid artery...
November 2018: Stroke; a Journal of Cerebral Circulation
Yi Luo, Huijie Ma, Jing-Jing Zhou, Lingyong Li, Shao-Rui Chen, Jixiang Zhang, Lin Chen, Hui-Lin Pan
Background and Purpose- Glutamate NMDARs (N-methyl-D-aspartate receptors) play a major role in the initiation of ischemic brain damage. However, NMDAR antagonists have no protective effects in stroke patients, possibly because they impair physiological functions of NMDARs. α2δ-1 (encoded by Cacna2d1) is strongly expressed in many brain regions. We determined the contribution of α2δ-1 to NMDAR hyperactivity and brain injury induced by ischemia and reperfusion. Methods- Mice were subjected to 90 minutes of middle cerebral artery occlusion followed by 24 hours of reperfusion...
October 2018: Stroke; a Journal of Cerebral Circulation
Qing-Fang Chen, Yu-Ying Liu, Chun-Shui Pan, Jing-Yu Fan, Li Yan, Bai-He Hu, Xin Chang, Quan Li, Jing-Yan Han
Background and Purpose- tPA (tissue-type plasminogen activator) is the only recommended intravenous thrombolytic agent for ischemic stroke. However, its application is limited because of increased risk of hemorrhagic transformation beyond the time window. T541 is a Chinese compound medicine with potential to attenuate ischemia and reperfusion injury. This study was to explore whether T541-benefited subjects underwent tPA thrombolysis extending the time window. Methods- Male C57BL/6 N mice were subjected to carotid artery thrombosis by stimulation with 10% FeCl3 followed by 10 mg/kg tPA with/without 20 mg/kg T541 intervention at 4...
September 2018: Stroke; a Journal of Cerebral Circulation
Jingyan Zhao, Hongfeng Mu, Liqiang Liu, Xiaoyan Jiang, Di Wu, Yejie Shi, Rehana K Leak, Xunming Ji
Ischemic injury can be alleviated by the judicious use of hypothermia. However, the optimal regimens and the temporal kinetics of post-stroke neurovascular responses to hypothermic intervention have not been systematically studied. These gaps slow the clinical translation of hypothermia as an anti-stroke therapy. Here, we characterized the effects of transient selective brain hypothermia (TSBH) from the hyperacute to chronic stages of focal ischemia/reperfusion brain injury induced by transient middle cerebral artery occlusion in mice...
October 18, 2018: Journal of Cerebral Blood Flow and Metabolism
Jae H Choi, John Pile-Spellman
Reperfusion is the first line of care in a growing number of eligible acute ischemic stroke patients. Early reperfusion with thrombolytic drugs and endovascular mechanical devices is associated with improved outcome and lower mortality rates compared with natural history. Reperfusion is not without risk, however, and may result in reperfusion injury, which manifests in hemorrhagic transformation, brain edema, infarct progression, and neurologic worsening. In this article, the functional and structural changes and underlying molecular mechanisms of ischemia and reperfusion are reviewed...
November 2018: Neuroimaging Clinics of North America
Yongying Hou, Ke Wang, Weijun Wan, Yue Cheng, Xia Pu, Xiufeng Ye
Ischemic stroke is a common disease with high mortality and morbidity worldwide. One of the important pathophysiological effects of ischemic stroke is apoptosis. A neuroprotective effect is defined as the inhibition of neuronal apoptosis to rescue or delay the infarction in the surviving ischemic penumbra. Resveratrol is a natural polyphenol that reportedly prevents cerebral ischemia injury by regulating the expression of PI3K/AKT/mTOR. Therefore, this study aimed to elucidate the neuroprotective effect of resveratrol on cerebral ischemia/reperfusion injury and to investigate the signaling pathways and mechanisms through which resveratrol regulates apoptosis in the ischemic penumbra...
September 2018: Genes & Diseases
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