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https://www.readbyqxmd.com/read/28632329/postictal-hypoperfusion-hypoxia-provides-the-foundation-for-a-unified-theory-of-seizure-induced-brain-abnormalities-and-behavioral-dysfunction
#1
REVIEW
Jordan S Farrell, Roberto Colangeli, Marshal D Wolff, Alexandra K Wall, Thomas J Phillips, Antis George, Paolo Federico, G Campbell Teskey
A recent article by Farrell et al. characterizes the phenomenon, mechanisms, and treatment of a local and severe hypoperfusion/hypoxia event that occurs in brain regions following a focal seizure. Given the well-established role of cerebral ischemia/hypoxia in brain damage and behavioral dysfunction in other clinical settings (e.g., stroke, cerebral vasospasm), we put forward a new theory: postictal hypoperfusion/hypoxia is responsible for the negative consequences associated with seizures. Fortunately, inhibition of two separate molecular targets, cyclooxygenase-2 (COX-2) and l-type calcium channels, can prevent the expression of postictal hypoperfusion/hypoxia...
June 20, 2017: Epilepsia
https://www.readbyqxmd.com/read/28629519/erythropoietin-endogenous-protection-of-ischemic-brain
#2
Robert T Mallet, Myoung-Gwi Ryou
The human brain requires uninterrupted delivery of blood-borne oxygen and nutrients to sustain its function. Focal ischemia, particularly, ischemic stroke, and global ischemia imposed by cardiac arrest disrupt the brain's fuel supply. The resultant ATP depletion initiates a complex injury cascade encompassing intracellular Ca(2+) overload, glutamate excitotoxicity, oxido-nitrosative stress, extracellular matrix degradation, and inflammation, culminating in neuronal and astroglial necrosis and apoptosis, neurocognitive deficits, and even death...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28625574/rapamycin-decreased-blood-brain-barrier-permeability-in-control-but-not-in-diabetic-rats-in-early-cerebral-ischemia
#3
Oak Z Chi, Geza K Kiss, Scott J Mellender, Xia Liu, Harvey R Weiss
Diabetes causes functional and structural changes in blood-brain barrier (BBB). The mammalian target of rapamycin (mTOR) has been associated with glucose metabolism, diabetes, and altering BBB permeability. Since there is only a narrow therapeutic window (3hours) for stroke victims, it is important to investigate BBB disruption in the early stage of cerebral ischemia. We compared the degree of BBB disruption in diabetic and in control rats at two hours of reperfusion after one hour of middle cerebral artery (MCA) occlusion with or without inhibition of mTOR...
June 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28620871/lipophilic-statins-and-the-risk-of-intracranial-hemorrhage-following-ischemic-stroke-a-population-based-study
#4
Kieran L Quinn, Erin M Macdonald, Muhammad M Mamdani, Christina Diong, David N Juurlink
BACKGROUND: Statins are commonly prescribed for the secondary prevention of ischemic stroke, but there is conflicting evidence as to whether they increase the risk of intracranial hemorrhage. Lipophilic statins cross the blood-brain barrier more freely than hydrophilic statins and may therefore increase the risk of intracranial hemorrhage. OBJECTIVE: To determine whether, in older patients following ischemic stroke, receipt of lipophilic statins was associated with differences in the risk of intracranial hemorrhage...
June 15, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28608237/exogenous-adipokine-peptide-resistin-protects-against-focal-cerebral-ischemia-reperfusion-injury-in-mice
#5
Jiangtao Zhu, Di Wu, Chenyu Zhao, Man Luo, Ronald C Hamdy, Balvin H L Chua, Xingshun Xu, Zhigang Miao
Previous studies have demonstrated that plasma resistin levels were increased in patients with acute ischemic stroke. However, the role of resistin after ischemic brain injury is still unclear. In this study, we investigated the protective effects of resistin on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that resistin (i.c.v.) significantly reduced infarct volume and improved neurological deficits after 45 min of ischemia and 24 h of reperfusion. Furthermore, our data demonstrate that intraperitoneal administration of resistin (10 µg/kg body weight) also had protective effects on infarct volume, indicating the crossing of resistin through the impaired BBB after ischemia injury...
June 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28607351/early-oxygen-therapy-does-not-protect-the-brain-from-vasogenic-edema-following-acute-ischemic-stroke-in-adult-male-rats
#6
Elmira Pasban, Hamdollah Panahpour, Akbar Vahdati
Brain edema aggravates primary brain injury and increases its mortality rate after ischemic stroke. It is believed that normobaric oxygen therapy (NBO) may produce neuroprotective effects against ischemic stroke; however, reports have been controversial, and its effects on vasogenic brain edema as a major complication of brain ischemia have not been clarified. The present study investigates the effects of NBO on cerebral edema and blood - brain barrier integrity using rat model of ischemic stroke. Transient focal cerebral ischemia was induced in adult male Sprague-Dawley rats by left middle cerebral artery occlusion (MCAO) for 90 min followed by 24 h reperfusion...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28603491/nosh-nbp-a-novel-nitric-oxide-and-hydrogen-sulfide-releasing-hybrid-attenuates-ischemic-stroke-induced-neuroinflammatory-injury-by-modulating-microglia-polarization
#7
Jing Ji, Pengjun Xiang, Tingting Li, Li Lan, Xiaole Xu, Guo Lu, Hui Ji, Yihua Zhang, Yunman Li
NOSH-NBP, a novel nitric oxide (NO) and hydrogen sulfide (H2S)-releasing hybrid, protects brain from ischemic stroke. This study mainly aimed to investigate the therapeutic effect of NOSH-NBP on ischemic stroke and the underlying mechanisms. In vivo, transient middle cerebral artery occlusion (tMCAO) was performed in C57BL/6 mice, with NO-NBP and H2S-NBP as controls. NO and H2S scavengers, carboxy-PTIO and BSS, respectively, were used to quench NO and H2S of NOSH-NBP. In vitro, BV2 microglia/BMDM were induced to the M1/2 phenotype, and conditioned medium (CM) experiments in BV2 microglia, neurons and b...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28603485/multifaceted-mechanisms-of-wy-14643-to-stabilize-the-blood-brain-barrier-in-a-model-of-traumatic-brain-injury
#8
Winfried Neuhaus, Tobias Krämer, Anja Neuhoff, Christina Gölz, Serge C Thal, Carola Y Förster
The blood-brain barrier (BBB) is damaged during ischemic insults such as traumatic brain injury or stroke. This contributes to vasogenic edema formation and deteriorate disease outcomes. Enormous efforts are pursued to understand underlying mechanisms of ischemic insults and develop novel therapeutic strategies. In the present study the effects of PPARα agonist WY-14643 were investigated to prevent BBB breakdown and reduce edema formation. WY-14643 inhibited barrier damage in a mouse BBB in vitro model of traumatic brain injury based on oxygen/glucose deprivation in a concentration dependent manner...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28602833/a-novel-il-1ra-pep-fusion-protein-with-enhanced-brain-penetration-ameliorates-cerebral-ischemia-reperfusion-injury-by-inhibition-of-oxidative-stress-and-neuroinflammation
#9
Dong-Dong Zhang, Min-Ji Zou, Ya-Tao Zhang, Wen-Liang Fu, Tao Xu, Jia-Xi Wang, Wen-Rong Xia, Zhi-Guang Huang, Xiang-Dong Gan, Xiao-Ming Zhu, Dong-Gang Xu
Neuroinflammation and oxidative stress are involved in cerebral ischemia-reperfusion, in which Interleukin 1 (IL-1), as an effective intervention target, is implicated. Interleukin-1 receptor antagonist (IL-1RA) is the natural inhibitor of IL-1, but blood-brain barrier (BBB) limits the brain penetration of intravenously administered IL-1RA, thereby restricting its therapeutic effect against neuroinflammation. In this study, we evaluated the potential effects of anti-inflammation and anti-oxidative stress of a novel protein IL-1RA-PEP, which fused IL-1RA with a cell penetrating peptide (CPP)...
June 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28601415/brain-autoimmunity-and-intestinal-microbiota-100-trillion-game-changers
#10
REVIEW
Hartmut Wekerle
T cells play a critical role in autoimmune diseases in the brain, particularly in multiple sclerosis (MS). Since T cells are normally prevented from crossing the blood-brain barrier (BBB), autoimmunity requires prior activation of naturally occurring autoreactive T cells in peripheral tissue. Recently, a critical role for the microbiota in this activation process has emerged. Here, we review the role of gut-associated lymphoid tissues (GALT) as a major site for the phenotypic changes that allow the migration of autoreactive T cells to the brain...
June 7, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28588054/sustained-neurological-recovery-after-stroke-in-aged-rats-treated-with-a-novel-prostacyclin-analog
#11
Changjun Yang, Kelly M DeMars, Jon C Alexander, Marcelo Febo, Eduardo Candelario-Jalil
BACKGROUND AND PURPOSE: Targeting the prostaglandin I2 prostanoid (IP) receptor to reduce stroke injury has been hindered by the lack of selective drugs. MRE-269 is the active metabolite of selexipag showing a high selectivity toward the IP receptor. Selexipag has been recently approved for clinical use in pulmonary hypertension. We hypothesized that postischemic treatment with MRE-269 provides long-lasting neuroprotection with improved neurological outcomes in a clinically relevant rat stroke model...
June 6, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28583195/effects-of-phosphodiesterase-3a-modulation-on-murine-cerebral-microhemorrhages
#12
Rachita K Sumbria, Vitaly Vasilevko, Mher Mahoney Grigoryan, Annlia Paganini-Hill, Ronald Kim, David H Cribbs, Mark J Fisher
BACKGROUND: Cerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects. As an initial step in the development of a therapy that simultaneously treats CMB and ischemic stroke, we hypothesized that inhibition of the PDE3A pathway is protective against CMH development...
June 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28580536/annexin-a2-plus-low-dose-tissue-plasminogen-activator-combination-attenuates-cerebrovascular-dysfunction-after-focal-embolic-stroke-of-rats
#13
Xiang Fan, Yinghua Jiang, Zhanyang Yu, Qi Liu, Shuzhen Guo, Xiaochuan Sun, Klaus van Leyen, MingMing Ning, Xiumei Gao, Eng H Lo, Xiaoying Wang
Previous studies showed recombinant annexin A2 (rA2) in combination with low-dose tissue-type plasminogen activator (tPA) improved thrombolytic efficacy and long-term neurological outcomes after embolic focal ischemia in rats. The objective of this study was to investigate the effects and mechanisms of the combination in early BBB integrity and cerebrovascular patency in the rat focal embolic stroke model. Ischemic brain infarct volume and hemorrhagic transformation were quantified at 24 h after stroke. At an earlier time point, 16 h after stroke, BBB integrity was evaluated by IgG extravasation, and the involved mechanisms were assessed for tight junction ZO-1 and adhesion junction ve-cadherin protein expression, matrix metalloproteinase activation, extracellular matrix collagen IV and endothelial barrier antigen expression, and activation of microglia/macrophages and astrocytes...
June 4, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28577991/inhibition-of-na-k-2cl-cotransporter-attenuates-blood-brain-barrier-disruption-in-a-mouse-model-of-traumatic-brain-injury
#14
Jun Zhang, Hongjian Pu, Haiyue Zhang, Zhishuo Wei, Xiaoyan Jiang, Mingyue Xu, Lili Zhang, Wenting Zhang, Jialin Liu, Hengxing Meng, R Anne Stetler, Dandan Sun, Jun Chen, Yanqin Gao, Ling Chen
Traumatic brain injury (TBI) can lead to long-term motor and cognitive dysfunction, which can be at least partly attributed to blood-brain barrier (BBB) disruption. The mechanisms underlying post-TBI BBB disruption, however, are poorly understood thus far. Na(+)-K(+)-2Cl(-) cotransporter isoform 1 (NKCC1) is a universally expressed ion transporter that maintains intracellular ion homeostasis by increasing intracellular K(+) and Cl(-). Having been characterized in stroke models, NKCC1 is activated in various cell types in the ischemic brain, and is thought to mediate BBB disruption, brain edema, and neuronal cell death...
May 31, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28572280/blood-brain-barrier-disruption-vascular-impairment-and-ischemia-reperfusion-damage-in-diabetic-stroke
#15
REVIEW
Poornima Venkat, Michael Chopp, Jieli Chen
No abstract text is available yet for this article.
June 1, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28569655/sustained-s-roscovitine-delivery-promotes-neuroprotection-associated-with-functional-recovery-and-decrease-in-brain-edema-in-a-randomized-blind-focal-cerebral-ischemia-study
#16
Estelle Rousselet, Anne Létondor, Bénédicte Menn, Yann Courbebaisse, Marie-Lise Quillé, Serge Timsit
Stroke is a devastating disorder that significantly contributes to death, disability and healthcare costs. In ischemic stroke, the only current acute therapy is recanalization, but the narrow therapeutic window less than 6 h limits its application. The current challenge is to prevent late cell death, with concomitant therapy targeting the ischemic cascade to widen the therapeutic window. Among potential neuroprotective drugs, cyclin-dependent kinase inhibitors such as (S)-roscovitine are of particular relevance...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28565759/oral-administration-of-ampelopsin-protects-against-acute-brain-injury-in-rats-following-focal-cerebral-ischemia
#17
Xiao-Li Ye, Ling-Qun Lu, Wei Li, Qi Lou, Hong-Gang Guo, Qiao-Juan Shi
Ampelopsin (AMP) is isolated from the Chinese medicinal herb Ampelopsis grossedentata (Hand-Mazz) and has been associated with numerous biological and pharmacological activities. However, it is not clear whether AMP has a direct protective effect on cerebral ischemia reperfusion injury. Therefore, the present study investigated its role in acute brain injury following focal cerebral ischemia in rats. The current study induced transient focal cerebral ischemia by performing middle cerebral artery occlusion (MCAO) for 60 min, followed by 24 h of reperfusion...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28553165/gsk-3%C3%AE-as-a-target-for-protection-against-transient-cerebral-ischemia
#18
Wei Wang, Mingchang Li, Yuefei Wang, Zhongyu Wang, Wei Zhang, Fangxia Guan, Qianxue Chen, Jian Wang
Stroke remains the leading cause of death and disability worldwide. This fact highlights the need to search for potential drug targets that can reduce stroke-related brain damage. We showed recently that a glycogen synthase kinase-3β (GSK-3β) inhibitor attenuates tissue plasminogen activator-induced hemorrhagic transformation after permanent focal cerebral ischemia. Here, we examined whether GSK-3β inhibition mitigates early ischemia-reperfusion stroke injury and investigated its potential mechanism of action...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28552908/xyloketal-b-alleviates-cerebral-infarction-and-neurologic-deficits-in-a-mouse-stroke-model-by-suppressing-the-ros-tlr4-nf-%C3%AE%C2%BAb-inflammatory-signaling-pathway
#19
Ni Pan, Liu-Yi Lu, Mei Li, Guo-Hao Wang, Fang-Yun Sun, Hong-Shuo Sun, Xue-Jun Wen, Jian-Ding Cheng, Jian-Wen Chen, Ji-Yan Pang, Jie Liu, Yong-Yuan Guan, Li-Yan Zhao, Wen-Liang Chen, Guan-Lei Wang
Xyloketal B (Xyl-B) is a novel marine compound isolated from mangrove fungus Xylaria sp. We previously demonstrated that pretreatment with Xyl-B exerted neuroprotective effects and attenuated hypoxic-ischemic brain injury in neonatal mice. In the present study we investigated the neuroprotective effects of pre- and post-treatment with Xyl-B in adult mice using a transient middle cerebral artery occlusion (tMCAO) model, and explored the underlying mechanisms. Adult male C57 mice were subjected to tMCAO surgery...
May 29, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28550144/exacerbation-of-oxygen-glucose-deprivation-induced-blood-brain-barrier-disruption-potential-pathogenic-role-of-interleukin-9-in-ischemic-stroke
#20
Sha Tan, Yilong Shan, Yuge Wang, Yinyao Lin, Siyuan Liao, Zhezhi Deng, Li Zhou, Wei Cai, Qin Zeng, Lei Zhang, Bingjun Zhang, Xuejiao Men, Haiyan Li, Xueqiang Hu, Changyou Wu, Lisheng Peng, Zhengqi Lu
Interleukin (IL) -9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke. We recruited 42 patients newly diagnosed with ischemic stroke and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3+CD4+IL-9+ and CD3+CD8+IL-9+ cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals...
May 26, 2017: Clinical Science (1979-)
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