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Stroke reperfusion injury

Qian Lu, Jihong Wang, Junshu Jiang, Shengnan Wang, Qilan Jia, Yue Wang, Weiping Li, Qin Zhou, Li Lv, Qingwei Li
BACKGROUND: The RGD-toxin protein Lj-RGD3 is a naturally occurring 118 amino acid peptide that can be obtained from the salivary gland of the Lampetra japonica fish. This unique peptide contains 3 RGD (Arg-Gly-Asp) motifs in its primary structure. Lj-RGD3 is available in recombinant form (rLj-RGD3) and can be produced in large quantities using DNA recombination techniques. The pharmacology of the three RGD motif-containing peptides has not been studied. This study investigated the protective effects of rLj-RGD3, a novel polypeptide, against ischemia/reperfusion-induced damage to the brain caused by middle cerebral artery occlusion (MCAO) in a rat stroke model...
2016: PloS One
Yuji Kaneko, Colleen Pappas, Naoki Tajiri, Cesar V Borlongan
Oxytocin protects against ischemia-induced inflammation and oxidative stress, and is associated with GABA (γ-aminobutyric acid, an inhibitory neurotransmitter) signaling transduction in neurons. However, the molecular mechanism by which oxytocin affords neuroprotection, especially the interaction between oxytocin receptor and GABAA receptor (GABAAR), remains to be elucidated. Primary rat neural cells were exposed to oxytocin before induction of experimental acute stroke model via oxygen-glucose deprivation-reperfusion (OGD/R) injury...
October 21, 2016: Scientific Reports
Stephen B Smith, Zhaobin Xu, Tatiana Novitskaya, Bo Zhang, Elena Chepurko, Xin-An Pu, Debra G Wheeler, Mark Ziolo, Richard J Gumina
AIMS: Prior work suggests that ischemic preconditioning increases the level of CD39 in the heart and contributes to cardiac protection. Therefore, we examined if targeted cardiac expression of CD39 protects against myocardial injury. MAIN METHODS: Mice with cardiac-specific expression of human CD39 (αMHC/hCD39-Tg) were generated, characterized and subjected to left coronary artery ischemia-reperfusion injury and infarct size at 24h following injury quantified. KEY FINDINGS: αMHC/hCD39-Tg mice have increased in cardiac ATPase and ADPase activity compared to WT littermates...
October 15, 2016: Life Sciences
Bo Liu, Fei Li, Jingshan Shi, Danli Yang, Yuanyuan Deng, Qihai Gong
Gastrodin (GAS), which is extracted from the Chinese herbal medicine Gastrodia elata Blume, has long been used to improve stroke, epilepsy, dizziness and dementia. However, the effects and underlying mechanisms of GAS on subacute phase cerebral ischemia‑reperfusion (I/R) injury remain unknown. The aim of the present study was to investigate the effects and mechanisms of GAS on cerebral I/R injury in rats. The rats were pretreated with GAS by gavage for 7 days followed by I/R surgery, and were then treated with GAS for 7 days after I/R surgery...
September 26, 2016: Molecular Medicine Reports
Hao Zhou, Wu-Shuang Yang, Ying Li, Tong Ren, Lu Peng, Han Guo, Jin-Feng Liu, Yu Zhou, Yun Zhao, Li-Chao Yang, Xin Jin
This study was carried out to investigate the exact mechanisms behind the neuroprotective effects of oleoylethanolamide (OEA) after acute cerebral ischemic injury. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion. OEA (40 mg/kg, ip) was administered with a single injection upon reperfusion. The number of apoptotic cells was detected by TUNEL staining. The expression of Bax, Bcl-2, and TLR4, as well as the activities of NF-κB, Akt, and ERK1/2 were analyzed by western blot...
October 13, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Yaqian Zhao, Guowei Huang, Shuang Chen, Yun Gou, Zhiping Dong, Xumei Zhang
Folic acid (FA) deficiency is not only associated with an increased risk of ischemic stroke, but also with increased oxidative DNA damage and brain injury after cerebral ischemia-reperfusion. However, the cellular and molecular mechanisms underlying FA deficiency-associated neuropathogenesis are not completely understood. In the present study, we tested the hypothesis that neuronal autophagy in focal cerebral ischemia rats may be involved in the mechanisms of FA deficiency-induced injury to neuronal cells. The results demonstrated that, accompanied by obvious neuron damage, the expression of the autophagic markers LC3 and Beclin-1, and the formation of 8-OHdG (a marker of oxidative stress to DNA) and autophagosomes were significantly increased in the brain cortex after ischemia-reperfusion...
September 7, 2016: Journal of Nutritional Biochemistry
Thorsten R Doeppner, Maria Doehring, Britta Kaltwasser, Arshad Majid, Fengyan Lin, Mathias Bähr, Ertugrul Kilic, Dirk M Hermann
In view of the failure of pharmacological therapies, alternative strategies promoting post-stroke brain repair are needed. Post-conditioning is a potentially promising therapeutic strategy, which induces acute neuroprotection against ischemic injury. To elucidate longer lasting actions of ischemic post-conditioning, mice were exposed to a 60-min stroke and post-conditioning by an additional 10-min stroke that was induced 10 min after reperfusion onset. Animals were sacrificed 24 h or 28 days post-stroke...
October 3, 2016: Molecular Neurobiology
Wei Cai, Kai Zhang, Peiying Li, Ling Zhu, Jing Xu, Boyu Yang, Xiaoming Hu, Zhengqi Lu, Jun Chen
Current understanding on the mechanisms of brain injury and neurodegeneration highlights an appreciation of multicellular interactions within the neurovascular unit (NVU), which include the evolution of blood-brain barrier (BBB) damage, neuronal cell death or degeneration, glial reaction, and immune cell infiltration. Aging is an important factor that influences the integrity of the NVU. The age-related physiological or pathological changes in the cellular components of the NVU have been shown to increase the vulnerability of the NVU to ischemia/reperfusion injury or neurodegeneration, and to result in deteriorated brain damage...
September 30, 2016: Ageing Research Reviews
Rongrong Zhang, Mengxue Xu, Yu Wang, Fei Xie, Gang Zhang, Xinyue Qin
Stroke is one of the leading causes of death and disability in the world. Oxidative stress, which refers to an excessive generation of reactive oxygen species (ROS), plays a key role in the pathological process of stroke. Excessive ROS production contributes to brain ischemia/reperfusion injury through many mechanisms including BBB disruption, inflammation, apoptosis, and cellular necrosis. Nuclear factor-E2-related factor 2 (Nrf2) is one of the critical regulators of endogenous antioxidant defense, which promote the transcription of a wide variety of antioxidant genes...
September 30, 2016: Molecular Neurobiology
Xuyan Jin, Yoo-Jin Shin, Tae-Ryong Riew, Jeong-Heon Choi, Mun-Yong Lee
Slit2, a secreted glycoprotein, has recently been implicated in the post-ischemic astroglial reaction. The objective of this study was to investigate the temporal changes and cellular localization of Slit2 and its receptors, Robo1, Robo2, and Robo4, in a rat transient focal ischemia model induced by middle cerebral artery occlusion. We used double- and triple-immunolabeling to determine the cell-specific changes in Slit2 and its receptors during a 10-week post-ischemia period. The expression profiles of Slit2 and the Robo receptors shared overlapping expression patterns in sham-operated and ischemic striatum...
September 29, 2016: Neurochemical Research
William T C Yuh, Matthew David Alexander, Toshihiro Ueda, Masayuki Maeda, Toshiaki Taoka, Kei Yamada, Norman J Beauchamp
OBJECTIVE: Advanced stroke imaging has generated much excitement for the early diagnosis of acute ischemic stroke (AIS) and facilitation of intervention. However, its therapeutic impact has not matched its diagnostic utility; most notably, lacking significant contributions to recent major AIS clinical trials. It is time to reexamine the fundamental hypotheses from the enormous body of imaging research on which clinical practices are based and reassess the current standard clinical and imaging strategies, or golden rules, established over decades for AIS...
September 28, 2016: AJR. American Journal of Roentgenology
Francesco Petrelli, Mirko Muzzi, Alberto Chiarugi, Giacinto Bagetta, Diana Amantea
Repurposing azithromycin has recently emerged as a promising strategy for the acute treatment of ischemic stroke. The mechanism of neuroprotection depends on the ability of this macrolide to promote polarization of microglia/macrophages towards beneficial M2 phenotypes. The immunomodulatory and anti-inflammatory effects of azithromycin, well documented in chronic inflammatory airway diseases, have been ascribed to the inhibition of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1...
September 20, 2016: European Journal of Pharmacology
Ozge Altintas, Mehmet Ozgen Altintas, Meltem Kumas, Talip Asil
OBJECTIVES: In this study, we aimed to evaluate the effect of the Ischemic preconditioning (IPreC) on the expression profile of cerebral miRNAs against stroke by induced transient middle cerebral artery occlusion (MCAo) in diabetic rats. METHODS: Eighty male Spraque Dawley rats were allocated to eight groups. In order to evaluate the expression profile of miRNAs, we induced transient MCAo seven days after STZ-induced diabetes (DM). Also we performed IPreC 72 h before transient MCAo to assess whether IPreC could have a neuroprotective effect against ischemia-reperfusion injury...
September 16, 2016: Neurological Research
Hong-Yan Li, Yan-Yan Su, Yun-Fang Zhang, Zhi-Qiang Liu, Bao-Jun Hua
Ischemia‑reperfusion (I/R) injury is important in the pathogenesis and/or progression of various diseases, including stroke, cardiovascular disease and acute renal injury. Increasing evidence indicates that atorvastatin exerts protective effects in I/R injury‑associated diseases; however, the underlying mechanisms remain to be fully elucidated. In the present study, oxygen‑glucose deprivation (OGD)/reperfusion‑stimulated. RAW264.7 murine macrophages served as a model of I/R injury. The knockdown of peroxisome proliferator activated receptor‑γ (PPARγ) expression in these cells increased OGD/reperfusion‑induced expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor‑α (TNF‑α) and interferon‑γ (IFN‑γ), and enhanced OGD/reperfusion‑induced downregulation of the expression of cluster of differentiation (CD) 206, at the mRNA and protein levels...
September 15, 2016: Molecular Medicine Reports
Chun-Ye Ma, Lin Yin
Angiotensin II type 2 receptor (AT2R) activation has been shown to protect against stroke, but its precise mechanism remains poorly understood. We investigated whether the protective effect of AT2R against ischemia/reperfusion injury is mediated by the suppression of immune and inflammatory responses. Rat models of middle cerebral artery occlusion were intraperitoneally injected with physiological saline, the AT2R agonist CGP42112 (1 mg/kg per day) or antagonist PD123319 (1 mg/kg per day). In the CGP42112 group, AT2R expression increased, the infarct area decreased, interleukin-1β and tumor necrosis factor-α expression decreased, and interleukin-10 expression increased compared with the saline group...
July 2016: Neural Regeneration Research
Paloma Patiño, Esther Parada, Victor Farré-Alins, Simone Molz, Ramón Cacabelos, José Marco-Contelles, Manuela G López, Carla I Tasca, Eva Ramos, Alejandro Romero, Javier Egea
Therapeutic interventions on pathological processes involved in the ischemic cascade, such as oxidative stress, neuroinflammation, excitotoxicity and/or apoptosis, are of urgent need for stroke treatment. Melatonin regulates a large number of physiological actions and its beneficial properties have been reported. The aim of this study was to investigate whether melatonin mediates neuroprotection in rat hippocampal slices subjected to oxygen-glucose-deprivation (OGD) and glutamate excitotoxicity. Thus, we describe here that melatonin significantly reduced the amount of lactate dehydrogenase released in the OGD-treated slices, reverted neuronal injury caused by OGD-reoxygenation in CA1 and CA3 hippocampal regions, restored the reduction of GSH content of the hippocampal slices induced by OGD, and diminished the oxidative stress produced in the reoxygenation period...
September 9, 2016: Neurotoxicology
Yueting Li, Yuan Lu, Jianchun Hu, Zipeng Gong, Wu Yang, Aimin Wang, Jiang Zheng, Ting Liu, Tingting Chen, Jie Hu, Ling Mi, Yongjun Li, Yanyu Lan, Yonglin Wang
Xin-Shao formula is a folk remedy widely used in China to prevent and cure stroke. Cerebral ischemic reperfusion (I/R) injury often takes place during the treatment of stroke. Information about the pharmacokinetic behavior of the remedy under cerebral I/R injury conditions is lacking. The present study aimed to compare the pharmacokinetic properties of scutellarin and paeoniflorin, two major bioactive components of Xin-Shao formula, under physiological state in cerebral I/R injury rats. Neurobehavioral dysfunction was evaluated and cerebral infarcted volume was measured in middle cerebral artery occlusion I/R injury (MCAO) rats...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Alireza Partoazar, Sanaz Nasoohi, Sayed Mehdi Rezayat, Kambiz Gilani, Shahram Ejtemaei Mehr, Amir Amani, Nastaran Rahimi, Ahmad Reza Dehpour
Cyclosporin A (CsA) is known as a neuroprotective agent against cerebral ischemia/reperfusion (I/R) in animal models. However, the significant therapeutic effects of CsA have been observed in high systemic doses or manipulating the blood brain barrier (BBB), resulting in systemic side effects and toxicity. Since the liposome nanocarries have been developed for efficient delivery of peptide and proteins, liposomal CsA (Lipo-CsA) could improve cerebral (I/R) injuries. In this study, the liposomal CsA formulation (CsA at dose of 2...
September 12, 2016: Fundamental & Clinical Pharmacology
Mei-Yin Chien, Cheng-Hung Chuang, Chang-Ming Chern, Kou-Tong Liou, Der-Zen Liu, Yu-Chang Hou, Yuh-Chiang Shen
Salvianolic acid A (SalA), a chemical type of caffeic acid trimer, has drawn great attention for its potent bioactivities against ischemia-induced injury both in vitro and in vivo. In this study, we evaluated SalA's protective effects against acute ischemic stroke by inducing middle cerebral artery occlusion/reperfusion (MCAO) injuries in mice. Treatment of the mice with SalA (50 and 100μg/kg, i.v.) at 2h after MCAO enhanced their survival rate, improved their moving activity, and ameliorated the severity of brain infarction and apoptosis seen in the mice by diminishing pathological changes such as the extensive breakdown of the blood-brain barrier (BBB), nitrosative stress, and the activation of an inflammatory transcriptional factor p65 nuclear factor-kappa B (NF-κB) and a pro-apoptotic kinase p25/Cdk5...
September 5, 2016: Free Radical Biology & Medicine
Jiayu Tang, Zhiping Hu, Jieqiong Tan, Sonlin Yang, Liuwang Zeng
Ischemic stroke results in severe brain damage and remains one of the leading causes of death and disability worldwide. Effective neuroprotective therapies are needed to reduce brain damage resulting from ischemic stroke. Mitochondria are crucial for cellular energy production and homeostasis. Modulation of mitochondrial function mediates neuroprotection against ischemic brain damage. Dynamin-related protein 1 (Drp1) and parkin play a key role in regulating mitochondrial dynamics. They are potential therapeutic targets for neuroprotection in ischemic stroke...
2016: Oxidative Medicine and Cellular Longevity
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