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Stroke reperfusion injury

Xiaoqin Zhang, Yiping Zhang, Songqi Tang, Lishuang Yu, Youqin Zhao, Qiangqiang Ren, Xiaoqiang Huang, Wen Xu, Mingqing Huang, Jun Peng
ETHNOPHARMACOLOGICAL RELEVANCE: Pien-Tze-Huang (PZH) is a famous formula of traditional Chinese medicine used to treating stroke. However, the protective effect of PZH and its mechanisms in acute ischemic stroke remain to be explored. AIM OF THE STUDY: To investigate the protective effect of PZH on neuronal apoptosis in acute cerebral ischemic injury rats and explore its underlying mechanisms. MATERIALS AND METHODS: The effects of PZH were studied in acute ischemic stroke rats induced by transient middle cerebral artery occlusion, and the mitochondria-mediated apoptotic proteins including cytochrome C (Cyt C), Bax, Bcl-xl, P53, caspase-3, and caspase-9 as well as AKT and glycogen synthase kinase-3 beta (GSK-3β) were assessed...
March 14, 2018: Journal of Ethnopharmacology
Attila Kiss, Huaqing Shu, Ouafa Hamza, David Santer, Eva Verena Tretter, Shanglong Yao, Klaus Markstaller, Seth Hallström, Bruno K Podesser, Klaus Ulrich Klein
OBJECTIVES: Previous studies demonstrated that preconditioning with argon gas provided a marked reduction in inflammation and apoptosis and increased myocardial contractility in the setting of acute myocardial ischaemia-reperfusion (IR). There is substantial evidence that myocardial IR injury following cardioplegic arrest is associated with the enhancement of apoptosis and inflammation, which is considered to play a role in cardiac functional impairment. Therefore, the present study was designed to clarify whether preconditioning with argon gas enhances recovery of cardiac function following cardioplegic arrest...
March 13, 2018: European Journal of Cardio-thoracic Surgery
Varinder Singh, Pawan Krishan, Richa Shri
Oxidative stress is strongly implicated in the pathogenesis of stroke. Strategies using antioxidants to improve neurological functions after stroke have, thus, gained significant attention. Ocimum basilicum L. is used traditionally to treat CNS disorders. Its antioxidant capacity is well established. Our laboratory has reported protective effects of pre-treatment with O. basilicum in experimental stroke, but its curative (post-treatment) effects in ischemic stroke have not been documented. Hence, the present study was aimed to evaluate the effect of O...
March 15, 2018: Metabolic Brain Disease
Hongbei Xu, Wenyi Qin, Xiao Hu, Song Mu, Jun Zhu, Wenhao Lu, Yong Luo
BACKGROUND: Ischemic stroke-induced neuroinflammation is mainly mediated by microglial cells. The nuclear factor kappa B (NF-κB) pathway is the key transcriptional pathway that initiates inflammatory responses following cerebral ischemia. OTULIN, a critical negative regulator of the NF-κΒ signaling pathway, exerts robust effects on peripheral immune cell-mediated inflammation and is regarded as an essential mediator for repressing inflammation in vivo. The effect of OTULIN on inflammatory responses in the central nervous system (CNS) was previously unstudied...
March 15, 2018: Journal of Neuroinflammation
Wen Zhang, Jun-Ke Song, Rong Yan, Li Li, Zhi-Yong Xiao, Wen-Xia Zhou, Zhen-Zhong Wang, Wei Xiao, Guan-Hua Du
Diterpene ginkgolides meglumine injection (DGMI) is a therapeutic extract of Ginkgo biloba L, which has been used for the treatment of cerebral ischemic stroke in China. Ginkgolides A, B and C are the main components of DGMI. This study was designed to investigate the neuroprotective effects of DGMI components against ischemic stroke in vivo and in vitro. Acute cerebral ischemic injury was induced in rats by occlusion of the middle cerebral artery (MCA) for 1.5 h followed by 24 h reperfusion. The rats were treated with DGMI (1, 3 and 10 mg/kg, iv) at the onset of reperfusion and 12 h after reperfusion...
March 15, 2018: Acta Pharmacologica Sinica
Yingying Liu, Yudiao Huang, Yueyue Xu, Peng Qu, Minghua Wang
Increased transendothelial permeability and subsequent blood-brain barrier damage play a key role in the pathological progression of human brain ischemia and secondary reperfusion. Memantine is a licensed drug providing clinically relevant efficacy in patients with Alzheimer's disease. However, little information is known regarding its effects on brain endothelial permeability. In this study, we investigated the effects of memantine on endothelial permeability and the underlying mechanisms in an ischemia-reperfusion (I/R) injury model in primary human brain microvascular endothelial cells...
March 15, 2018: IUBMB Life
Huisheng Wu, Chaoliang Tang, Lydia Wai Tai, Weifeng Yao, Peipei Guo, Junmou Hong, Xin Yang, Xinyi Li, Zhao Jin, Jianjuan Ke, Yanlin Wang
Background & Aims:  Ischemic stroke has been ranked the second cause of death in patients worldwide.Inflammation which is activated during cerebral ischemia/reperfusion is an important mechanism leading to brain injury. This study aimed to investigate the effect of flurbiprofen axetil on cerebral I/R injury and the role of inflammation in this process. Methods:  Rats were subjected to sham operation or global cerebral I/R with or without flurbiprofen axetil (5 mg/kg or 10 mg/kg). Global cerebral ischemia was achieved by occlusion of bilateral common carotid arteries combined with hypotension for 20 min followed by reperfusion for 72 h...
March 14, 2018: Bioscience Reports
Matthew B Bevers, Thomas W K Battey, Ann-Christin Ostwaldt, Reza Jahan, Jeffrey L Saver, W Taylor Kimberly, Chelsea S Kidwell
BACKGROUND: Apparent diffusion coefficient (ADC) imaging is a biomarker of cytotoxic injury that predicts edema formation and outcome after ischemic stroke. It therefore has the potential to serve as a "tissue clock" to describe the extent of ischemic injury and potentially predict response to therapy. The goal of this study was to determine the relationship between baseline ADC signal intensity, revascularization, and edema formation. METHODS: We examined the ADC signal intensity ratio (ADCr) of the stroke lesion (defined as the baseline DWI hyperintense region) compared to the contralateral normal hemisphere in 65 subjects from the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy trial...
March 13, 2018: Cerebrovascular Diseases
Yu Mao, Qiuyue Kong, Rongrong Li, Xiaojin Zhang, Yali Gui, Yuehua Li, Chuanfu Li, Yanlin Zhao, Li Liu, Zhengnian Ding
Heat shock protein A12A (HSPA12A) is a newly discovered member of the Hsp70 family. The biological characteristics and functional roles of HSPA12A are poorly understood. This study investigated the effects of HSPA12A on ischaemic stroke in mice. Ischaemic stroke was induced by left middle cerebral artery occlusion for 1 h followed by blood reperfusion. We observed that HSPA12A was highly expressed in brain neurons, and neuronal HSPA12A expression was downregulated by ischaemic stroke and stroke-associated risk factors (aging, obesity and hyperglycaemia)...
March 9, 2018: Biochimica et Biophysica Acta
Kelly M DeMars, Austin O McCrea, David M Siwarski, Brian D Sanz, Changjun Yang, Eduardo Candelario-Jalil
Ischemic stroke occurs when a clot forms in the brain vasculature that starves downstream tissue of oxygen and nutrients resulting in cell death. The tissue immediately downstream of the blockage, the core, dies within minutes, but the surrounding tissue, the penumbra is potentially salvageable. Prostaglandin E2 binds to four different G-protein coupled membrane receptors EP1-EP4 mediating different and sometimes opposing responses. Pharmacological activation of the EP4 receptor has already been established as neuroprotective in stroke, but the mechanism(s) of protection are not well-characterized...
2018: Frontiers in Neuroscience
Shuai Zhang, Qier An, Tianfu Wang, Shuping Gao, Guangqian Zhou
Post-stroke hyperglycemia during early reperfusion increases blood-brain barrier (BBB) permeability and subsequently aggravates brain injury and clinical prognosis. The decreased level of tight junction proteins (TJPs) has been reported but the underlying mechanism remains largely elusive. Herein we designed to investigate the detailed molecular events in brain microvascular endothelial cells (BMECs) ex and in vivo. After oxygen-glucose deprivation (OGD) for 90 min and reperfusion with 8 or 16 mM glucose for 30 min, glucose at 16 mM caused significant decrease of the TJP expression and particularly ZO-1 redistribution from membrane to cytoplasm of BMECs...
March 7, 2018: Neuroscience
Yu Shuang Tian, Di Zhong, Qing Qing Liu, Xiu Li Zhao, Hong Xue Sun, Jing Jin, Hai Ning Wang, Guo Zhong Li
OBJECTIVE Ischemic stroke remains a significant cause of death and disability in industrialized nations. Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) of the JAK2/STAT3 pathway play important roles in the downstream signal pathway regulation of ischemic stroke-related inflammatory neuronal damage. Recently, microRNAs (miRNAs) have emerged as major regulators in cerebral ischemic injury; therefore, the authors aimed to investigate the underlying molecular mechanism between miRNAs and ischemic stroke, which may provide potential therapeutic targets for ischemic stroke...
March 9, 2018: Journal of Neurosurgery
Xuewen Wei, JuanJuan Gong, Juyun Ma, Taiyu Zhang, Yihang Li, Ting Lan, Peng Guo, Suhua Qi
It is well known that Wnt5a activation plays a pivotal role in brain injury and β-arrestin2 induces c-Jun N-terminal kinase (JNK3) activation is involved in neuronal cell death. Nonetheless, the relationship between Wnt5 and JNK3 remains unexplored during cerebral ischemia/reperfusion (I/R). In the present study, we tested the hypothesis that Wnt5a-mediated JNK3 activation via the Wnt5a- Dvl-1-β-arrestin2-JNK3 signaling pathway was correlated with I/R brain injury. We found that cerebral I/R could enhance the assembly of the Dvl-1-β-arrestin2-JNK3 signaling module, Dvl-1 phosphorylation and JNK3 activation...
March 3, 2018: Neuropharmacology
Chengli Ling, Jianming Liang, Chun Zhang, Ruixiang Li, Qianqian Mou, Jin Qin, Xiaofang Li, Jianxin Wang
Ischemic stroke (IS) is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. It has been a worldwide critical disease threatening to the health and life of human beings. Despite significant progresses achieved, effective treatment still remains a formidable challenge due to the complexity of the disease. Salvianolic acid B (Sal-B) and Puerarin (Pue) are two active neuroprotectants isolated from traditional Chinese herbs, Salvia miltiorrhiza and Kudzu root respectively, which have been used for the prevention and treatment of IS for thousands of years in China...
March 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yan-Ping Luo, Hong Zhang, Han-Fei Hu, Ze-Yu Cao, Xin-Zhuang Zhang, Liang Cao, Zhen-Zhong Wang, Wei Xiao
To investigate the protective effects of ginkgo diterpene lactone meglumine injection (GDLMI) on cerebral focal ischemia reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats, and explore its possible mechanism. One hundred and forty male SD rats were randomly divided into sham operation group, model group, ginkgo biloba extract injection (Ginaton, 1.0 mL•kg⁻¹) group, nimodipine (0.4 mg•kg⁻¹) group, and GDLMI (5.2, 2.6, 1.3 mg•kg⁻¹) groups; All of rats received corresponding drugs by tail vein injection 4 days before operation (normal saline in model group and sham operation group)...
December 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Huijun Wu, Hui Liu, Fengtong Zuo, Lihua Zhang
Cerebral ischemia injury is a clinical, frequently occurring disease, which causes a heavy burden on society and families. It has been demonstrated that cytosolic phospholipase A2α (cPLA2α) is significant in neurological injury caused by ischemic brain injury, and inhibition of cPLA2α may reduce stroke injury. In the present study, the role of cPLA2α was investigated in a mouse model of middle cerebral artery occlusion and/or reperfusion (MCAO/R) using an effective cPLA2α inhibitor and adenoviruses‑mediated RNA interference...
February 15, 2018: Molecular Medicine Reports
Cai-Jun Xie, Ai-Ping Gu, Jun Cai, Yi Wu, Rui-Cong Chen
Background and Purpose: Curcumin, a natural antioxidant isolated from Curcuma longa, has been reported to exert neuroprotective effect in animal models of ischemic stroke. However, the underlying mechanism is still not fully understood. The purpose of this study was to investigate the effect of curcumin treatment on neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion (I/R) injury and in mouse N2a cells after oxygen-glucose deprivation/reoxygenation (OGD/R) injury and its underlying mechanism...
February 2018: Brain and Behavior
Guo-Qiang Yuan, Song Gao, Yong-Jian Geng, Yao-Ping Tang, Min-Juan Zheng, Harnath S Shelat, Scott Collins, Han-Jing Wu, Yi-Ling Wu
Background: Our previous studies have shown that Tongxinluo (TXL), a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density (MVD) in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection...
March 5, 2018: Chinese Medical Journal
Carolina Tecuatl, Gabriel Herrrera-López, Alejandro Martín-Ávila, Bocheng Yin, Stephen Weber, Germán Barrionuevo, Emilio J Galván
The selective vulnerability of hippocampal area CA1 to ischemia-induced injury is a well-known phenomenon. However, the cellular mechanisms that confer resistance to area CA3 against ischemic damage remain elusive. Here, we show that oxygen-glucose deprivation-reperfusion (OGD-RP), an in vitro model that mimic the pathological conditions of the ischemic stroke, increases the phosphorylation level of Tropomyosin-receptor-kinase B (TrkB) in area CA3. Slices preincubated with Brain-derived neurotrophic factor (BDNF) or 7,8-Dihydroxyflavone (7,8-DHF) exhibited reduced depression of the electrical activity triggered by OGD-RP...
February 26, 2018: European Journal of Neuroscience
Megan A Evans, Hyun Ah Kim, Yeong Hann Ling, Sandy Uong, Antony Vinh, T Michael De Silva, Thiruma V Arumugam, Andrew N Clarkson, Graeme R Zosky, Grant R Drummond, Brad R S Broughton, Christopher G Sobey
Acute inflammation can exacerbate brain injury after ischemic stroke. Beyond its well-characterized role in calcium metabolism, it is becoming increasingly appreciated that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-VitD3 ), has potent immunomodulatory properties. Here, we aimed to determine whether 1,25-VitD3 supplementation could reduce subsequent brain injury and associated inflammation after ischemic stroke. Male C57Bl6 mice were randomly assigned to be administered either 1,25-VitD3 (100 ng/kg/day) or vehicle i...
February 23, 2018: Neuromolecular Medicine
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