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Author: Ian Sutcliffe Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
Hypothermia has long been known to be neuroprotective following brain injury, yet the correlates of this neuroprotection are poorly understood. We postulated that moderate hypothermia would attenuate leukocyte rolling and adhesion following IL-1beta or cerebral ischemia induced inflammation. Laser Doppler was used to demonstrate successful induction of global cerebral ischemia in C57/B16 mice. ISEL, NeuN, and GFAP staining of brain sections were used to demonstrate temporal and spatial injury in this murine model of 10-minutes global cerebral ischemia. Four hours hypothermia (32°C) induced immediately following normothermic (37°C) cerebral ischemia provided protection against cell death and astrocytosis for up to 7 days post-ischemia. An open cranial window and intravital microscopy were used to visualize leukocyte rolling and adhesion in pial venules at 4-h following injection of IL-1beta, and 0 to 4-h following global cerebral ischemia. Increases in leukocyte rolling and adhesion were observed in IL-1beta injected mice. Four hours of hypothermia begun immediately following injection of IL-1beta reduced both rolling and adhesion. Similarly, increases in leukocyte rolling and adhesion were observed at 0-h and 2-h following cerebral ischemia in normothermic mice, and 2-h of post-ischemic hypothermia reduced both rolling and adhesion. In contrast, MPO and neutrophil immunohistochemistry showed that no significant infiltration of neutrophils into the brain following global cerebral ischemia. Molecular mechanisms of hypothermic effects were investigated in vitro. We showed that neither IL-1beta nor hypothermia altered the expression of CD18, or chemotaxis in human neutrophils. Together, these findings suggest that one mechanism by which hypothermia may provide neuroprotection is by reduction of leukocyte-endothelial interactions in the cerebromicrovasculature.
Author: Ian Sutcliffe Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
Hypothermia has long been known to be neuroprotective following brain injury, yet the correlates of this neuroprotection are poorly understood. We postulated that moderate hypothermia would attenuate leukocyte rolling and adhesion following IL-1beta or cerebral ischemia induced inflammation. Laser Doppler was used to demonstrate successful induction of global cerebral ischemia in C57/B16 mice. ISEL, NeuN, and GFAP staining of brain sections were used to demonstrate temporal and spatial injury in this murine model of 10-minutes global cerebral ischemia. Four hours hypothermia (32°C) induced immediately following normothermic (37°C) cerebral ischemia provided protection against cell death and astrocytosis for up to 7 days post-ischemia. An open cranial window and intravital microscopy were used to visualize leukocyte rolling and adhesion in pial venules at 4-h following injection of IL-1beta, and 0 to 4-h following global cerebral ischemia. Increases in leukocyte rolling and adhesion were observed in IL-1beta injected mice. Four hours of hypothermia begun immediately following injection of IL-1beta reduced both rolling and adhesion. Similarly, increases in leukocyte rolling and adhesion were observed at 0-h and 2-h following cerebral ischemia in normothermic mice, and 2-h of post-ischemic hypothermia reduced both rolling and adhesion. In contrast, MPO and neutrophil immunohistochemistry showed that no significant infiltration of neutrophils into the brain following global cerebral ischemia. Molecular mechanisms of hypothermic effects were investigated in vitro. We showed that neither IL-1beta nor hypothermia altered the expression of CD18, or chemotaxis in human neutrophils. Together, these findings suggest that one mechanism by which hypothermia may provide neuroprotection is by reduction of leukocyte-endothelial interactions in the cerebromicrovasculature.
Author: Mathilde Chevin Publisher: ISBN: Category : Languages : en Pages :
Book Description
"Neonatal encephalopathy (NE) and neonatal arterial ischemic stroke (NAIS) are either diffuse or focal brain injuries resulting both from hypoxic-ischemic events and/or pathogen-induced inflammation. NE affects up to 1% of live births. NAIS affects 0.3% of live births. Treatment options are symptomatic in both diseases. A curative therapeutic option is only available in NE due to pure HI and consists in therapeutic hypothermia (HT). HT, however, provides limited neuroprotection and around 50% of treated neonates will experience moderate to severe neurologic disabilities. It is still unclear if HT confers beneficial effects when there is combined aggression of hypoxia-ischemia (HI) and pathogen-induced inflammation, which is one of the most common pathophysiological scenario of both NE and NAIS.Human neuropathological studies and experimental animal models of perinatal brain injury reveal that Interleukin (IL)-1[beta] – among other pro-inflammatory cytokines – is implicated in the pathophysiological cascade leading to brain injury. Besides, preclinical studies did not bring evidence of an effect of HT on the IL-1 cascade. Therefore, postnatal systemic administration of Interleukine-1 receptor antagonist (IL-1Ra: a natural blocker of IL-1) may be a potential therapeutic intervention of postnatal brain injury, such as NE and NAIS. However, IL-1Ra is not approved for the treatment or prevention of postnatal brain injury, and further studies are needed to determine its safety and efficacy. No studies have been conducted to assess the efficacy of IL-1Ra with other therapies, such as HT.In this thesis, I hypothesized that HT alone or in combination with IL-1Ra would provide neuroprotective effects in a rat model of both NE and NAIS resulting from inflammatory-sensitized-HI. We further hypothesized that IL-1Ra will provide an added value to HT in alleviating brain injuries and improving motor behavioural outcomes. I aimed to investigate (1) the safety of HT treatment in combination with IL-1Ra and (2) the efficacy of HT combined or not with IL-1Ra in terms of mortality, brain injuries, and short and long-term motor behaviour in our model of NE resulting from inflammatory-sensitized HI. This thesis shows for the first time that (i) HT has an impact on the pharmacodynamic parameters of IL-1Ra; revealing a future need to refine the dose of IL-1Ra used in combination to HT; (ii) this combined therapy is able to reduce the mortality rate and improve short-term motor behaviour; and (iii) HT alone reduces the occurrence and the volume of brain infarct, improves brain metabolic activity, and alleviates the long-term motor outcomes of inflammatory plus HI- induced brain injuries.This thesis reveals the importance of studying the influence of HT on the distribution, metabolism, elimination and clinical efficacy of drugs in order to avoid toxicity or ineffectiveness. Current and future studies investigating the beneficial effect of HT in other neurological pathologies, such as stroke, subarachnoid hemorrhage, traumatic brain injury, and spinal cord injury, should take into account this particular effect. In addition, we observed a potential combined effect of IL-1Ra plus HT that needs further preclinical evaluation before moving to human clinical therapeutic trials. Our results provide evidence of the neuroprotective effect of HT in NE and NAIS resulting from inflammatory-sensitized HI. This thesis opens new research avenues on the potential benefit of HT in other postnatal brain injury sharing common determinants with NE, such as NAIS. This could pave the way towards further clinical evaluation of the benefit of HT in NAIS"--
Author: Giuseppe Buonocore Publisher: Springer ISBN: 9783319294872 Category : Medical Languages : en Pages : 0
Book Description
This landmark book, a reference work now in its second edition, provides healthcare practitioners in neonatology with an up-to-date, comprehensive source of readily accessible practical advice that will assist in the expert management of patients and their diverse illnesses. Leading experts in their fields discuss the underlying causes and mechanisms and all aspects of the treatment of the full range of neonatal diseases and abnormalities, citing the evidence base whenever appropriate. In addition, detailed information is provided on epidemiology and fetal medicine; therapeutic issues such as the organization of care, transport services, and home care after discharge; legal issues; nutrition; and the consequences of medication use during pregnancy, maternal drug abuse and smoking, and maternal diabetes. The inclusion of summaries, tables, and carefully selected guidelines and recommendations will supply practitioners with quick references and instant solutions during daily practice. The book will be a superb resource for all involved in the care of newborn babies, including neonatologists, pediatricians, pediatric surgeons, anesthesiologists, midwives, and nursing staff. It is published within the SpringerReference program, which delivers access to living editions constantly updated through a dynamic peer-review publishing process.
Author: Oliver Lowry Publisher: Elsevier ISBN: 0323156711 Category : Science Languages : en Pages : 304
Book Description
A Flexible System of Enzymatic Analysis is a multipurpose manual of laboratory methods that offers a systematic scheme for the analysis of biological materials from the level of the wholeorgan down to the single cell and beyond. It intends to guide the development of methods, the refinement of old ones, and the adaptation in general of methods to almost any scale of sensitivity. This manual is organized into three parts: a general section, one on quantitative histochemistry, and an appendix containing information that may be useful to have at the bench. The general section is comprised of nine chapters that focus on properties of the pyridine nucleotides, kinetics, and glassware, as well as on improvement, modification, adaptation, trouble shooting, and development of methods. This part also describes the preparation of tissues for analysis, the enzymatic cycling methods, and a compendium of 36 metabolite assays. The quantitative histochemistry section is comprised of four chapters that include information on the preparation of frozen-dried material and dissection of samples for analysis; the fishpole balance for weighing samples; and the generalities of analysis with emphasis on the ""oil well technique."" This book will be useful to novices as well as experts who are familiar with other analytical styles.
Author: Ulrich Dirnagl Publisher: Springer Science & Business Media ISBN: 3662054264 Category : Medical Languages : en Pages : 248
Book Description
The successful treatment of acute stroke remains one of the major challenges in clinical medicine. Over the last decades, the understanding of stroke pathophysiology has greatly improved, while the therapeutic options in stroke therapy remain very limited. Today, hyperacute mechanisms of damage, such as excitotoxicity, can be discriminated from delayed ones, such as inflammation and apoptosis. Targeting of inflammation has already been successfully applied in various stroke models, but translation into a clinically efficacious strategy has not been achieved so far. In this book, leading experts in basic cerebrovascular research as well as stroke treatment review the current evidence for and against an important role for inflammation in stroke, and explore the potential of treating or modulating inflammation in stroke therapy.
Author: National Research Council Publisher: National Academies Press ISBN: 030916785X Category : Science Languages : en Pages : 223
Book Description
Expanding on the National Research Council's Guide for the Care and Use of Laboratory Animals, this book deals specifically with mammals in neuroscience and behavioral research laboratories. It offers flexible guidelines for the care of these animals, and guidance on adapting these guidelines to various situations without hindering the research process. Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research offers a more in-depth treatment of concerns specific to these disciplines than any previous guide on animal care and use. It treats on such important subjects as: The important role that the researcher and veterinarian play in developing animal protocols. Methods for assessing and ensuring an animal's well-being. General animal-care elements as they apply to neuroscience and behavioral research, and common animal welfare challenges this research can pose. The use of professional judgment and careful interpretation of regulations and guidelines to develop performance standards ensuring animal well-being and high-quality research. Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research treats the development and evaluation of animal-use protocols as a decision-making process, not just a decision. To this end, it presents the most current, in-depth information about the best practices for animal care and use, as they pertain to the intricacies of neuroscience and behavioral research.
Author: Jeffrey Noebels Publisher: OUP USA ISBN: 0199746540 Category : Medical Languages : en Pages : 1258
Book Description
Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.
Author: Ian Sutcliffe
Author: Ian Sutcliffe![The Effects of Moderate Hypothermia on IL-1[beta] and Ischemia-induced Cerebral Inflammation in C57/B16 Mice PDF](https://books.google.com/books/content/images/frontcover/v7l5NwAACAAJ?fife=w80-h100)
Author: Ian Sutcliffe
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