oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Does anesthetic provide similar neuroprotection to therapeutic hypothermia after cardiac arrest?
Hong Zhang
Critical Care , 2010, DOI: 10.1186/cc8923
Abstract: Therapeutic hypothermia has been shown to provide neuroprotection against ischemic injury after cardiac arrest in in vitro and in vivo models. In the previous issue of Critical Care, Meybohm and colleagues [1] demonstrate that cardiac arrest triggers the release of cerebral inflammatory cytokines in pigs' cerebral cortex. Therapeutic hypothermia alters inflammatory response in cardiac arrest and subsequent cardiopulmonary resuscitation. The combination of hypothermia with sevoflurane post-conditioning does not confer additional anti-inflammatory effects compared with hypothermia alone.Cardiac arrest remains the leading cause of death in the US and Europe, with an out-of-hospital cardiac arrest survival-to-discharge rate of less than 10%. In-hospital cardiac arrest presents a dismal prognosis. According to a large in-hospital registry, the survival-to-discharge rate is 18%, whereas that of a developing country is 6.9% [2,3]. Without prompt care, the chance for meaningful survival falls dramatically within minutes of arrest onset. When immediate care is available and victims are successfully resuscitated, the majority of these initial survivors subsequently suffer crippling neurologic injury or die in the few days following the cardiac arrest event. Thus, improving survival and brain function after initial resuscitation from cardiac arrest remains a critical challenge. Therapeutic hypothermia, introduced more than six decades ago, remains an important neuroprotective factor in cardiac arrest. Laboratory studies have demonstrated that cooling after resuscitation from cardiac arrest improves both survival as well as subsequent neurologic and cardiac function and has few side effects. these findings have been reproduced using a variety of cooling techniques in different species, including rats, dogs, and pigs.However, physician use of hypothermia induction in patients resuscitated from cardiac arrest is low. In 2003, Abella and colleagues [4] reported that 87% of US phys
Wnt1 Neuroprotection Translates into Improved Neurological Function during Oxidant Stress and Cerebral Ischemia Through AKT1 and Mitochondrial Apoptotic Pathways  [PDF]
Zhao Zhong Chong,Yan Chen Shang,Jinling Hou,Kenneth Maiese
Oxidative Medicine and Cellular Longevity , 2010, DOI: 10.4161/oxim.3.2.11758
Abstract: Although essential for the development of the nervous system, Wnt1 also has been associated with neurodegenerative disease and cognitive loss during periods of oxidative stress. Here we show that endogenous expression of Wnt1 is suppressed during oxidative stress in both in vitro and in vivo experimental models. Loss of endogenous Wnt1 signaling directly correlates with neuronal demise and increased functional deficit, illustrating that endogenous neuronal Wnt1 offers a vital level of intrinsic cellular protection against oxidative stress. Furthermore, transient overexpression of Wnt1 or application of exogenous Wnt1 recombinant protein is necessary to preserve neurological function and rescue neurons from apoptotic membrane phosphatidylserine externalization and genomic DNA degradation, since blockade of Wnt1 signaling with a Wnt1 antibody or dickkopf related protein 1 abrogates neuronal protection by Wnt1. Wnt1 ultimately relies upon the activation of Akt1, the modulation of mitochondrial membrane permeability, and the release of cytochrome c to control the apoptotic cascade, since inhibition of Wnt1 signaling, the phosphatidylinositol 3-kinase pathway, or Akt1 activity abrogates the ability of Wnt1 to block these apoptotic components. Our work identifies Wnt1 and its downstream signaling as cellular targets with high clinical potential for novel treatment strategies for multiple disorders precipitated by oxidative stress.
Wnt1 Neuroprotection Translates into Improved Neurological Function during Oxidant Stress and Cerebral Ischemia Through AKT1 and Mitochondrial Apoptotic Pathways  [PDF]
Zhao Zhong Chong,Yan Chen Shang,Jinling Hou,Kenneth Maiese
Oxidative Medicine and Cellular Longevity , 2010, DOI: 10.4161/oxim.3.2.11758
Abstract: Although essential for the development of the nervous system, Wnt1 also has been associated with neurodegenerative disease and cognitive loss during periods of oxidative stress. Here we show that endogenous expression of Wnt1 is suppressed during oxidative stress in both in vitro and in vivo experimental models. Loss of endogenous Wnt1 signaling directly correlates with neuronal demise and increased functional deficit, illustrating that endogenous neuronal Wnt1 offers a vital level of intrinsic cellular protection against oxidative stress. Furthermore, transient overexpression of Wnt1 or application of exogenous Wnt1 recombinant protein is necessary to preserve neurological function and rescue neurons from apoptotic membrane phosphatidylserine externalization and genomic DNA degradation, since blockade of Wnt1 signaling with a Wnt1 antibody or dickkopf related protein 1 abrogates neuronal protection by Wnt1. Wnt1 ultimately relies upon the activation of Akt1, the modulation of mitochondrial membrane permeability, and the release of cytochrome c to control the apoptotic cascade, since inhibition of Wnt1 signaling, the phosphatidylinositol 3-kinase pathway, or Akt1 activity abrogates the ability of Wnt1 to block these apoptotic components. Our work identifies Wnt1 and its downstream signaling as cellular targets with high clinical potential for novel treatment strategies for multiple disorders precipitated by oxidative stress.
Human Neural Stem Cells Over-Expressing VEGF Provide Neuroprotection, Angiogenesis and Functional Recovery in Mouse Stroke Model  [PDF]
Hong J. Lee, Kwang S. Kim, In H. Park, Seung U. Kim
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000156
Abstract: Background Intracerebral hemorrhage (ICH) is a lethal stroke type. As mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs) selectively migrate to the brain and induce behavioral recovery in rat ICH model, and that combined administration of NSCs and vascular endothelial growth factor (VEGF) results in improved structural and functional outcome from cerebral ischemia. Methods and Findings We postulated that human NSCs overexpressing VEGF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs, increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by unilateral injection of bacterial collagenase into striatum. HB1.F3.VEGF human NSC line produced an amount of VEGF four times higher than parental F3 cell line in vitro, and induced behavioral improvement and 2–3 fold increase in cell survival at two weeks and eight weeks post-transplantation. Conclusions Brain transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results suggest a possible application of the human neural stem cell line, which is genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke.
Stroke Neuroprotection: Targeting Mitochondria  [PDF]
Lora Talley Watts,Reginald Lloyd,Richard Justin Garling,Timothy Duong
Brain Sciences , 2013, DOI: 10.3390/brainsci3020540
Abstract: Stroke is the fourth leading cause of death and the leading cause of long-term disability in the United States. Blood flow deficit results in an expanding infarct core with a time-sensitive peri-infarct penumbra that is considered salvageable and is the primary target for treatment strategies. The only current FDA-approved drug for treating ischemic stroke is recombinant tissue plasminogen activator (rt-PA). However, this treatment is limited to within 4.5 h of stroke onset in a small subset of patients. The goal of this review is to focus on mitochondrial-dependent therapeutic agents that could provide neuroprotection following stroke. Dysfunctional mitochondria are linked to neurodegeneration in many disease processes including stroke. The mechanisms reviewed include: (1) increasing ATP production by purinergic receptor stimulation, (2) decreasing the production of ROS by superoxide dismutase, or (3) increasing antioxidant defenses by methylene blue, and their benefits in providing neuroprotection following a stroke.
Aerobic production and utilization of lactate satisfy increased energy demands upon neuronal activation in hippocampal slices and provide neuroprotection against oxidative stress  [PDF]
Avital Schurr,Evelyne Gozal
Frontiers in Pharmacology , 2012, DOI: 10.3389/fphar.2011.00096
Abstract: Ever since it was shown for the first time that lactate can support neuronal function in vitro as a sole oxidative energy substrate, investigators in the field of neuroenergetics have been debating the role, if any, of this glycolytic product in cerebral energy metabolism. Our experiments employed the rat hippocampal slice preparation with electrophysiological and biochemical methodologies. The data generated by these experiments (a) support the hypothesis that lactate, not pyruvate, is the end-product of cerebral aerobic glycolysis; (b) indicate that lactate plays a major and crucial role in affording neural tissue to respond adequately to glutamate excitation and to recover unscathed post-excitation; (c) suggest that neural tissue activation is accompanied by aerobic lactate and NADH production, the latter being produced when the former is converted to pyruvate by mitochondrial lactate dehydrogenase (mLDH); (d) imply that NADH can be utilized as an endogenous scavenger of reactive oxygen species (ROS) to provide neuroprotection against ROS-induced neuronal damage.
Neuroprotection in Stroke: Past, Present, and Future  [PDF]
Arshad Majid
ISRN Neurology , 2014, DOI: 10.1155/2014/515716
Abstract: Stroke is a devastating medical condition, killing millions of people each year and causing serious injury to many more. Despite advances in treatment, there is still little that can be done to prevent stroke-related brain damage. The concept of neuroprotection is a source of considerable interest in the search for novel therapies that have the potential to preserve brain tissue and improve overall outcome. Key points of intervention have been identified in many of the processes that are the source of damage to the brain after stroke, and numerous treatment strategies designed to exploit them have been developed. In this review, potential targets of neuroprotection in stroke are discussed, as well as the various treatments that have been targeted against them. In addition, a summary of recent progress in clinical trials of neuroprotective agents in stroke is provided. 1. Introduction Stroke is one of the leading causes of death and disability worldwide. Despite decades of research, however, treatment options remain limited. In ischemic stroke, the primary focus of treatment is reperfusion. Currently, the only drug approved for the treatment of ischemic stroke is recombinant tissue plasminogen activator (rtPA, alteplase), which has a limited time window for administration and increases the risk for subsequent hemorrhage. Consequently, only a small percentage of patients receive rtPA treatment [1]. While this treatment is effective in opening up occluded cerebral vessels in some patients and can lead to improved outcomes after ischemic stroke, there are currently no approved treatments for the myriad of damaging pathological processes that persist in the brain long after the acute stage. These include the processes of inflammation, excitotoxicity, oxidative stress, apoptosis, and edema resulting from disruption of the blood-brain barrier [2]. In hemorrhagic stroke, additional processes include physical damage from the mass of accumulated blood itself, cytotoxicity of blood components, and vasospasm in subarachnoid hemorrhage [3, 4]. A considerable amount of research has been invested into the development of novel treatments capable of protecting the brain from damage following stroke, with limited success. Numerous neuroprotective treatments have been identified that show great promise in animal models of stroke. Unfortunately, nearly all have failed to provide protection in human trials. The purpose of this review is to provide an overview of targets for neuroprotection in stroke and examples of current research on potential neuroprotective treatments.
Neuroprotection in glaucoma  [cached]
Vasudevan Sushil,Gupta Viney,Crowston Jonathan
Indian Journal of Ophthalmology , 2011,
Abstract: Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells and their axons. Recent evidence suggests that intraocular pressure (IOP) is only one of the many risk factors for this disease. Current treatment options for this disease have been limited to the reduction of IOP; however, it is clear now that the disease progression continues in many patients despite effective lowering of IOP. In the search for newer modalities in treating this disease, much data have emerged from experimental research the world over, suggesting various pathological processes involved in this disease and newer possible strategies to treat it. This review article looks into the current understanding of the pathophysiology of glaucoma, the importance of neuroprotection, the various possible pharmacological approaches for neuroprotection and evidence of current available medications.
Melatonin-Based Therapeutics for Neuroprotection in Stroke  [PDF]
Kazutaka Shinozuka,Meaghan Staples,Cesar V. Borlongan
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms14058924
Abstract: The present review paper supports the approach to deliver melatonin and to target melatonin receptors for neuroprotection in stroke. We discuss laboratory evidence demonstrating neuroprotective effects of exogenous melatonin treatment and transplantation of melatonin-secreting cells in stroke. In addition, we describe a novel mechanism of action underlying the therapeutic benefits of stem cell therapy in stroke, implicating the role of melatonin receptors. As we envision the clinical entry of melatonin-based therapeutics, we discuss translational experiments that warrant consideration to reveal an optimal melatonin treatment strategy that is safe and effective for human application.
Absence of AKT1 Mutations in Glioblastoma  [PDF]
Fonnet E. Bleeker, Simona Lamba, Carlo Zanon, Angela A. van Tilborg, Sieger Leenstra, Dirk Troost, Theo Hulsebos, W. Peter Vandertop, Alberto Bardelli
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005638
Abstract: Background Oncogenic activation of the PI3K signalling pathway plays a pivotal role in the development of glioblastoma multiforme (GBM). A central node in PI3K downstream signalling is controlled by the serine-threonine kinase AKT1. A somatic mutation affecting residue E17 of the AKT1 gene has recently been identified in breast and colon cancer. The E17K change results in constitutive AKT1 activation, induces leukaemia in mice, and accordingly, may be therapeutically exploited to target the PI3K pathway. Assessing whether AKT1 is activated by somatic mutations in GBM is relevant to establish its role in this aggressive disease. Methodology/Principal Findings We performed a systematic mutational analysis of the complete coding sequence of the AKT1 gene in a panel of 109 tumor GBM samples and nine high grade astrocytoma cell lines. However, no somatic mutations were detected in the coding region of AKT1. Conclusions/Significance Our data indicate that in GBM oncogenic deregulation of the PI3K pathway does not involve somatic mutations in the coding region of AKT1.
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.