A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model

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C.C. Chen

2014-10-01

Full Text Available We developed a forced non-electric-shock running wheel (FNESRW system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h. An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS, an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05 and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model.

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Chen, C C; Chang, M W; Chang, C P; Chan, S C; Chang, W Y; Yang, C L; Lin, M T

2014-10-01

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model

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Chen, C.C. [Department of Electrical Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Chang, M.W. [Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan (China); Chang, C.P. [Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan (China); Chan, S.C.; Chang, W.Y.; Yang, C.L. [Department of Electrical Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Lin, M.T. [Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan (China)

2014-08-15

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

Association between acute statin therapy, survival, and improved functional outcome after ischemic stroke: the North Dublin Population Stroke Study.

LENUS (Irish Health Repository)

2011-04-01

Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study.

Gait analysis in a pre- and post-ischemic stroke biomedical pig model.

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Duberstein, Kylee Jo; Platt, Simon R; Holmes, Shannon P; Dove, C Robert; Howerth, Elizabeth W; Kent, Marc; Stice, Steven L; Hill, William D; Hess, David C; West, Franklin D

2014-02-10

Severity of neural injury including stroke in human patients, as well as recovery from injury, can be assessed through changes in gait patterns of affected individuals. Similar quantification of motor function deficits has been measured in rodent animal models of such injuries. However, due to differences in fundamental structure of human and rodent brains, there is a need to develop a large animal model to facilitate treatment development for neurological conditions. Porcine brain structure is similar to that of humans, and therefore the pig may make a more clinically relevant animal model. The current study was undertaken to determine key gait characteristics in normal biomedical miniature pigs and dynamic changes that occur post-neural injury in a porcine middle cerebral artery (MCA) occlusion ischemic stroke model. Yucatan miniature pigs were trained to walk through a semi-circular track and were recorded with high speed cameras to detect changes in key gait parameters. Analysis of normal pigs showed overall symmetry in hindlimb swing and stance times, forelimb stance time, along with step length, step velocity, and maximum hoof height on both fore and hindlimbs. A subset of pigs were again recorded at 7, 5 and 3 days prior to MCA occlusion and then at 1, 3, 5, 7, 14 and 30 days following surgery. MRI analysis showed that MCA occlusion resulted in significant infarction. Gait analysis indicated that stroke resulted in notable asymmetries in both temporal and spatial variables. Pigs exhibited lower maximum front hoof height on the paretic side, as well as shorter swing time and longer stance time on the paretic hindlimb. These results support that gait analysis of stroke injury is a highly sensitive detection method for changes in gait parameters in pig. Copyright © 2013 Elsevier Inc. All rights reserved.

Present Status and Future Challenges of New Therapeutic Targets in Preclinical Models of Stroke in Aged Animals with/without Comorbidities

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Aurel Popa-Wagner

2018-01-01

Full Text Available The aging process, comorbidities, and age-associated diseases are closely dependent on each other. Cerebral ischemia impacts a wide range of systems in an age-dependent manner. However, the aging process has many facets which are influenced by the genetic background and epigenetic or environmental factors, which can explain why some people age differently than others. Therefore, there is an urgent need to identify age-related changes in body functions or structures that increase the risk for stroke and which are associated with a poor outcome. Multimodal imaging, electrophysiology, cell biology, proteomics, and transcriptomics, offer a useful approach to link structural and functional changes in the aging brain, with or without comorbidities, to post-stroke rehabilitation. This can help us to improve our knowledge about senescence firstly, and in this context, aids in elucidating the pathophysiology of age-related diseases that allows us to develop therapeutic strategies or prevent diseases. These processes, including potential therapeutical interventions, need to be studied first in relevant preclinical models using aged animals, with and without comorbidities. Therefore, preclinical research on ischemic stroke should consider age as the most important risk factor for cerebral ischemia. Furthermore, the identification of effective therapeutic strategies, corroborated with successful translational studies, will have a dramatic impact on the lives of millions of people with cerebrovascular diseases.

Critical periods after stroke study: translating animal stroke recovery experiments into a clinical trial

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Dromerick, Alexander W.; Edwardson, Matthew A.; Edwards, Dorothy F.; Giannetti, Margot L.; Barth, Jessica; Brady, Kathaleen P.; Chan, Evan; Tan, Ming T.; Tamboli, Irfan; Chia, Ruth; Orquiza, Michael; Padilla, Robert M.; Cheema, Amrita K.; Mapstone, Mark E.; Fiandaca, Massimo S.; Federoff, Howard J.; Newport, Elissa L.

2015-01-01

Introduction: Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS) is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 h of upper extremity therapy either immediately upon rehab admission, 2–3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial. PMID

Critical Periods after Stroke Study: Translating animal stroke recovery experiments into a clinical trial

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Alexander W Dromerick

2015-04-01

Full Text Available Introduction: 795,000 Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 hours of upper extremity therapy either immediately upon rehab admission, 2-3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test at one year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial.

Middle cerebral artery occlusion in Macaca fascicularis: acute and chronic stroke evolution.

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D'Arceuil, Helen E; Duggan, Michael; He, Julian; Pryor, Johnny; de Crespigny, Alex

2006-04-01

An intravascular stroke model designed for magnetic resonance imaging was developed in Macaca fascicularis (M. fascicularis) to characterize serial stroke lesion evolution. This model produces a range of stroke lesion sizes which closely mimics human stroke evolution. This paper describes the care of animals undergoing this stroke procedure, the range of outcomes we experienced and the cause of mortality in this model. Anesthesia was induced with atropine and ketamine and maintained with isoflurane or propofol. Non-invasive blood pressure, oxygen saturation, heart rate, respiration rate, temperature and end tidal CO2 were monitored continuously. The stroke was created by occluding a distal branch of the middle cerebral artery. During catheter placement animals were heparinized and vasospasm was minimized using verapamil. Anesthetic induction and maintenance were smooth. Animals with small strokes showed very rapid recovery, were able to ambulate and self-feed within 2 hours of recovery. Animals with strokes of >or=4% of the hemispheric volume required lengthy observation during recovery and parenteral nutrition. Large strokes resulted in significant brain edema, herniation and brainstem compression. Intracerebral hemorrhage and or subarachnoid hemorrhage coupled with a stroke of any size was acutely fatal. In the absence of an effective acute stroke therapy, the spectrum of outcomes seen in our primate model is very similar to that observed in human stroke patients.

Stroke Lesions in a Large Upper Limb Rehabilitation Trial Cohort Rarely Match Lesions in Common Preclinical Models

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Edwardson, Matthew A.; Wang, Ximing; Liu, Brent; Ding, Li; Lane, Christianne J.; Park, Caron; Nelsen, Monica A.; Jones, Theresa A; Wolf, Steven L; Winstein, Carolee J; Dromerick, Alexander W.

2017-01-01

Background Stroke patients with mild-moderate upper extremity (UE) motor impairments and minimal sensory and cognitive deficits provide a useful model to study recovery and improve rehabilitation. Laboratory-based investigators use lesioning techniques for similar goals. Objective Determine whether stroke lesions in an UE rehabilitation trial cohort match lesions from the preclinical stroke recovery models used to drive translational research. Methods Clinical neuroimages from 297 participants enrolled in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study were reviewed. Images were characterized based on lesion type (ischemic or hemorrhagic), volume, vascular territory, depth (cortical gray matter, cortical white matter, subcortical), old strokes, and leukoaraiosis. Lesions were compared with those of preclinical stroke models commonly used to study upper limb recovery. Results Among the ischemic stroke participants, median infarct volume was 1.8 mL, with most lesions confined to subcortical structures (61%) including the anterior choroidal artery territory (30%) and the pons (23%). Of ICARE participants, stroke patients, but they represent a clinically and scientifically important subgroup. Compared to lesions in general stroke populations and widely-studied animal models of recovery, ICARE participants had smaller, more subcortically-based strokes. Improved preclinical-clinical translational efforts may require better alignment of lesions between preclinical and human stroke recovery models. PMID:28337932

Stroke survivors' endorsement of a "stress belief model" of stroke prevention predicts control of risk factors for recurrent stroke.

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Phillips, L Alison; Tuhrim, Stanley; Kronish, Ian M; Horowitz, Carol R

2014-01-01

Perceptions that stress causes and stress-reduction controls hypertension have been associated with poorer blood pressure (BP) control in hypertension populations. The current study investigated these "stress-model perceptions" in stroke survivors regarding prevention of recurrent stroke and the influence of these perceptions on patients' stroke risk factor control. Stroke and transient ischemic attack survivors (N=600) participated in an in-person interview in which they were asked about their beliefs regarding control of future stroke; BP and cholesterol were measured directly after the interview. Counter to expectations, patients who endorsed a "stress-model" but not a "medication-model" of stroke prevention were in better control of their stroke risk factors (BP and cholesterol) than those who endorsed a medication-model but not a stress-model of stroke prevention (OR for poor control=.54, Wald statistic=6.07, p=.01). This result was not explained by between group differences in patients' reported medication adherence. The results have implications for theory and practice, regarding the role of stress belief models and acute cardiac events, compared to chronic hypertension.

Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages

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Hsiao-Wen Lin

2009-03-01

Full Text Available Hsiao-Wen Lin, E-Jian LeeNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, TaiwanAbstract: Melatonin (N-acetyl-5-methoxy-tryptamine, a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood–brain barrier (BBB. Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.Keywords: cerebral ischemia, melatonin, stroke, neuroprotection

Effects of stroke education using an animated cartoon and a manga on elementary school children.

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Sakamoto, Yuki; Yokota, Chiaki; Miyashita, Fumio; Amano, Tatsuo; Shigehatake, Yuya; Oyama, Satoshi; Itagaki, Naruhiko; Okumura, Kosuke; Toyoda, Kazunori; Minematsu, Kazuo

2014-08-01

Stroke education for the youth is expected to reduce prehospital delay by informing the bystander of appropriate action to take and providing knowledge to prevent onset of stroke in future. Previously, we developed effective teaching materials consisting of an animated cartoon and a Manga for junior high school students. The aim of this study was to evaluate the feasibility and effectiveness of our educational materials for stroke education taught by schoolteachers to elementary school children. Using our teaching materials, a 30-minute lesson was given by trained general schoolteachers. Questionnaires on stroke knowledge (symptoms and risk factors) and action to take on identification of suspected stroke symptoms were filled out by school children before, immediately after, and at 3 months after completion of the lesson. A total of 219 children (aged 10 or 11 years) received the stroke lesson. Stroke knowledge significantly increased immediately after the lesson compared with before (symptoms, P Manga that was previously used for junior high school students was feasible for elementary school children. However, revision of the materials is required for better retention of stroke knowledge for children. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Efficacy of Alteplase in a Mouse Model of Acute Ischemic Stroke: A Retrospective Pooled Analysis.

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Orset, Cyrille; Haelewyn, Benoit; Allan, Stuart M; Ansar, Saema; Campos, Francesco; Cho, Tae Hee; Durand, Anne; El Amki, Mohamad; Fatar, Marc; Garcia-Yébenes, Isaac; Gauberti, Maxime; Grudzenski, Saskia; Lizasoain, Ignacio; Lo, Eng; Macrez, Richard; Margaill, Isabelle; Maysami, Samaneh; Meairs, Stephen; Nighoghossian, Norbert; Orbe, Josune; Paramo, Jose Antonio; Parienti, Jean-Jacques; Rothwell, Nancy J; Rubio, Marina; Waeber, Christian; Young, Alan R; Touzé, Emmanuel; Vivien, Denis

2016-05-01

The debate over the fact that experimental drugs proposed for the treatment of stroke fail in the translation to the clinical situation has attracted considerable attention in the literature. In this context, we present a retrospective pooled analysis of a large data set from preclinical studies, to examine the effects of early versus late administration of intravenous recombinant tissue-type plasminogen activator. We collected data from 26 individual studies from 9 international centers (13 researchers; 716 animals) that compared recombinant tissue-type plasminogen activator with controls, in a unique mouse model of thromboembolic stroke induced by an in situ injection of thrombin into the middle cerebral artery. Studies were classified into early (stroke in mice. The power analysis reveals that a multicenter trial would require 123 animals per group instead of 40 for a single-center trial. © 2016 American Heart Association, Inc.

Motor Cortex and Motor Cortical Interhemispheric Communication in Walking After Stroke: The Roles of Transcranial Magnetic Stimulation and Animal Models in Our Current and Future Understanding.

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Charalambous, Charalambos C; Bowden, Mark G; Adkins, DeAnna L

2016-01-01

Despite the plethora of human neurophysiological research, the bilateral involvement of the leg motor cortical areas and their interhemispheric interaction during both normal and impaired human walking is poorly understood. Using transcranial magnetic stimulation (TMS), we have expanded our understanding of the role upper-extremity motor cortical areas play in normal movements and how stroke alters this role, and probed the efficacy of interventions to improve post-stroke arm function. However, similar investigations of the legs have lagged behind, in part, due to the anatomical difficulty in using TMS to stimulate the leg motor cortical areas. Additionally, leg movements are predominately bilaterally controlled and require interlimb coordination that may involve both hemispheres. The sensitive, but invasive, tools used in animal models of locomotion hold great potential for increasing our understanding of the bihemispheric motor cortical control of walking. In this review, we discuss 3 themes associated with the bihemispheric motor cortical control of walking after stroke: (a) what is known about the role of the bihemispheric motor cortical control in healthy and poststroke leg movements, (b) how the neural remodeling of the contralesional hemisphere can affect walking recovery after a stroke, and (c) what is the effect of behavioral rehabilitation training of walking on the neural remodeling of the motor cortical areas bilaterally. For each theme, we discuss how rodent models can enhance the present knowledge on human walking by testing hypotheses that cannot be investigated in humans, and how these findings can then be back-translated into the neurorehabilitation of poststroke walking. © The Author(s) 2015.

Animal Robot Assisted-therapy for Rehabilitation of Patient with Post-Stroke Depression

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Zikril Zulkifli, Winal; Shamsuddin, Syamimi; Hwee, Lim Thiam

2017-06-01

Recently, the utilization of therapeutic animal robots has expanded. This research aims to explore robotics application for mental healthcare in Malaysia through human-robot interaction (HRI). PARO, the robotic seal PARO was developed to give psychological effects on humans. Major Depressive Disorder (MDD) is a common but severe mood disorder. This study focuses on the interaction protocol between PARO and patients with MDD. Initially, twelve rehabilitation patients gave subjective evaluation on their first interaction with PARO. Next, therapeutic interaction environment was set-up with PARO in it to act as an augmentation strategy with other psychological interventions for post-stroke depression. Patient was exposed to PARO for 20 minutes. The results of behavioural analysis complemented with information from HRI survey question. The analysis also observed that the individual interactors engaged with the robot in diverse ways based on their needs Results show positive reaction toward the acceptance of an animal robot. Next, therapeutic interaction is set-up for PARO to contribute as an augmentation strategy with other psychological interventions for post-stroke depression. The outcome is to reduce the stress level among patients through facilitated therapy session with PARO

Active Compounds of Rhubarb Root and Rhizome in Animal Model Experiments of Focal Cerebral Ischemia

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Ai-ju Liu

2015-01-01

Full Text Available Rhubarb root and rhizome (RRR has been clinically used for stroke at least 2000 years and is still used in modern times in both China and elsewhere worldwide. The objective of present study was to evaluate the efficacy of active compounds of RRR (ACRRR for experimental ischemic stroke. Studies of ACRRR in animal models of ischemic stroke were identified from 5 databases until April 2014. Study quality for each included article was evaluated according to the CAMARADES 10-item checklist. Outcome measures were neurological deficit score and infarct size. All the data were analyzed using RevMan 5.1 software. As a result, 20 studies were identified describing procedures involving 577 animals. The quality score of studies ranges from 2 to 6, and the median was 3.4. Six studies showed significant effects of ACRRR for improving infarct size compared with model group (P<0.01. Six studies indicated significant effects of ACRRR for improving the neurological deficit scores according to Zea longa criterion or eight-point criterion (P<0.01. In conclusion, these findings demonstrated a possible efficacy of ACRRR that have potential neuroprotective effect for experimental ischemic stroke. However, these apparently positive findings should be interpreted with caution because of the methodological flaws.

Neuroprotection for Stroke: Current Status and Future Perspectives

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Christoph Kleinschnitz

2012-09-01

Full Text Available Neuroprotection aims to prevent salvageable neurons from dying. Despite showing efficacy in experimental stroke studies, the concept of neuroprotection has failed in clinical trials. Reasons for the translational difficulties include a lack of methodological agreement between preclinical and clinical studies and the heterogeneity of stroke in humans compared to homogeneous strokes in animal models. Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria. However, there are a number of neuroprotective treatments under investigation in clinical trials such as hypothermia and ebselen. Moreover, promising neuroprotective treatments based on a deeper understanding of the complex pathophysiology of ischemic stroke such as inhibitors of NADPH oxidases and PSD-95 are currently evaluated in preclinical studies. Further concepts to improve translation include the investigation of neuroprotectants in multicenter preclinical Phase III-type studies, improved animal models, and close alignment between clinical trial and preclinical methodologies. Future successful translation will require both new concepts for preclinical testing and innovative approaches based on mechanistic insights into the ischemic cascade.

The role of sleep in recovery following ischemic stroke: A review of human and animal data

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Simone B. Duss

2017-01-01

Full Text Available Despite advancements in understanding the pathophysiology of stroke and the state of the art in acute management of afflicted patients as well as in subsequent neurorehabilitation training, stroke remains the most common neurological cause of long-term disability in adulthood. To enhance stroke patients’ independence and well-being it is necessary, therefore, to consider and develop new therapeutic strategies and approaches. We postulate that sleep might play a pivotal role in neurorehabilitation following stroke. Over the last two decades compelling evidence for a major function of sleep in neuroplasticity and neural network reorganization underlying learning and memory has evolved. Training and learning of new motor skills and knowledge can modulate the characteristics of subsequent sleep, which additionally can improve memory performance. While healthy sleep appears to support neuroplasticity resulting in improved learning and memory, disturbed sleep following stroke in animals and humans can impair stroke outcome. In addition, sleep disorders such as sleep disordered breathing, insomnia, and restless legs syndrome are frequent in stroke patients and associated with worse recovery outcomes. Studies investigating the evolution of post-stroke sleep changes suggest that these changes might also reflect neural network reorganization underlying functional recovery. Experimental and clinical studies provide evidence that pharmacological sleep promotion in rodents and treatment of sleep disorders in humans improves functional outcome following stroke. Taken together, there is accumulating evidence that sleep represents a “plasticity state” in the process of recovery following ischemic stroke. However, to test the key role of sleep and sleep disorders for stroke recovery and to better understand the underlying molecular mechanisms, experimental research and large-scale prospective studies in humans are necessary. The effects of hospital

Neuroserpin polymorphisms and stroke risk in a biracial population: the stroke prevention in young women study

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Stern Barney J

2007-10-01

Full Text Available Abstract Background Neuroserpin, primarily localized to CNS neurons, inhibits the adverse effects of tissue-type plasminogen activator (tPA on the neurovascular unit and has neuroprotective effects in animal models of ischemic stroke. We sought to evaluate the association of neuroserpin polymorphisms with risk for ischemic stroke among young women. Methods A population-based case-control study of stroke among women aged 15–49 identified 224 cases of first ischemic stroke (47.3% African-American and 211 age-matched control subjects (43.1% African-American. Neuroserpin single nucleotide polymorphisms (SNPs chosen through HapMap were genotyped in the study population and assessed for association with stroke. Results Of the five SNPs analyzed, the A allele (frequency; Caucasian = 0.56, African-American = 0.42 of SNP rs6797312 located in intron 1 was associated with stroke in an age-adjusted dominant model (AA and AT vs. TT among Caucasians (OR = 2.05, p = 0.023 but not African-Americans (OR = 0.71, p = 0.387. Models adjusting for other risk factors strengthened the association. Race-specific haplotype analyses, inclusive of SNP rs6797312, again demonstrated significant associations with stroke among Caucasians only. Conclusion This study provides the first evidence that neuroserpin is associated with early-onset ischemic stroke among Caucasian women.

Impact of Stroke Therapy Academic Industry Roundtable (STAIR) Guidelines on Peri-Anesthesia Care for Rat Models of Stroke: A Meta-Analysis Comparing the Years 2005 and 2015.

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Thomas, Aurelie; Detilleux, Johann; Flecknell, Paul; Sandersen, Charlotte

2017-01-01

Numerous studies using rats in stroke models have failed to translate into successful clinical trials in humans. The Stroke Therapy Academic Industry Roundtable (STAIR) has produced guidelines on the rodent stroke model for preclinical trials in order to promote the successful translation of animal to human studies. These guidelines also underline the importance of anaesthetic and monitoring techniques. The aim of this literature review is to document whether anaesthesia protocols (i.e., choice of agents, mode of ventilation, physiological support and monitoring) have been amended since the publication of the STAIR guidelines in 2009. A number of articles describing the use of a stroke model in adult rats from the years 2005 and 2015 were randomly selected from the PubMed database and analysed for the following parameters: country where the study was performed, strain of rats used, technique of stroke induction, anaesthetic agent for induction and maintenance, mode of intubation and ventilation, monitoring techniques, control of body temperature, vascular accesses, and administration of intravenous fluids and analgesics. For each parameter (stroke, induction, maintenance, monitoring), exact chi-square tests were used to determine whether or not proportions were significantly different across year and p values were corrected for multiple comparisons. An exact p-test was used for each parameter to compare the frequency distribution of each value followed by a Bonferroni test. The level of significant set at guidelines appear to have had no effect on the anaesthetic and monitoring techniques in rats undergoing experimental stroke induction, despite the publication of said guidelines in 2009.

Changes in neuronal properties and spinal reflexes during development of spasticity following spinal cord lesions and stroke: studies in animal models and patients.

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Hultborn, Hans

2003-05-01

It is a well-known fact that spinal reflexes may gradually change and often become enhanced following spinal cord lesions. Although these phenomena are known, the underlying mechanisms are still unknown and under investigation, mainly in animal models. Over the last twenty years, new methods have been developed that can reliably estimate the activity of specific spinal pathways in humans at rest and during voluntary movement. These methods now make it possible to describe components of the spinal pathophysiology in spasticity in humans following spinal lesions or stroke. We now know that spinal networks are capable of generating the basic pattern of locomotion in a large number of vertebrates, including the monkey--and in all likelihood, humans. Although spinal networks are capable of generating locomotor-like activity in the absence of afferent signals, functional gait is not possible without sensory feedback. The results of animal studies on the sensory control of and the transmitter systems involved in the spinal locomotor centers are now being used to improve rehabilitation of walking in persons with spinal cord injury and hemiplegia.

Fluoxetine Maintains a State of Heightened Responsiveness to Motor Training Early After Stroke in a Mouse Model.

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Ng, Kwan L; Gibson, Ellen M; Hubbard, Robert; Yang, Juemin; Caffo, Brian; O'Brien, Richard J; Krakauer, John W; Zeiler, Steven R

2015-10-01

Data from both humans and animal models suggest that most recovery from motor impairment after stroke occurs in a sensitive period that lasts only weeks and is mediated, in part, by an increased responsiveness to training. Here, we used a mouse model of focal cortical stroke to test 2 hypotheses. First, we investigated whether responsiveness to training decreases over time after stroke. Second, we tested whether fluoxetine, which can influence synaptic plasticity and stroke recovery, can prolong the period over which large training-related gains can be elicited after stroke. Mice were trained to perform a skilled prehension task to an asymptotic level of performance after which they underwent stroke induction in the caudal forelimb area. The mice were then retrained after a 1- or 7-day delay with and without fluoxetine. Recovery of prehension after a caudal forelimb area stroke was complete if training was initiated 1 day after stroke but incomplete if it was delayed by 7 days. In contrast, if fluoxetine was administered at 24 hours after stroke, then complete recovery of prehension was observed even with the 7-day training delay. Fluoxetine seemed to mediate its beneficial effect by reducing inhibitory interneuron expression in intact premotor cortex rather than through effects on infarct volume or cell death. There is a gradient of diminishing responsiveness to motor training over the first week after stroke. Fluoxetine can overcome this gradient and maintain maximal levels of responsiveness to training even 7 days after stroke. © 2015 American Heart Association, Inc.

Effect of helicopter transport on neurological outcomes in a mouse model of embolic stroke with reperfusion: AIR-MICE pilot study.

Science.gov (United States)

Leira, Enrique C; Zaheer, Asgar; Schnell, Thomas; Torner, James C; Olalde, Heena M; Pieper, Andrew A; Ortega-Gutierrez, Santiago; Nagaraja, Nandakumar; Marks, Nancy L; Adams, Harold P

2015-10-01

Patients often suffer a stroke at a significant distance from a center capable of delivering endovascular therapy, thus requiring rapid transport by helicopter emergency medical services while receiving a recombinant tissue plasminogen activator infusion that was initiated locally. But little is known about how a helicopter flight may impact the safety and efficacy of recombinant tissue plasminogen activator-induced reperfusion and patient outcomes. To establish a new animal method to address with fidelity the safety and overall effect of helicopter emergency medical services during thrombolysis. Prospective randomized open blinded end-point study of an actual helicopter flight exposure. Adult C57BL/6 male mice were treated with a 10 mg/kg recombinant tissue plasminogen activator infusion two-hours after an embolic middle cerebral artery occlusion. Mice were randomized in pairs to simultaneously receive the infusion during a local helicopter flight or in a ground hangar. Eighteen mice (nine pairs) were analyzed. The paired t-test analysis showed nonsignificant smaller infarction volumes in the helicopter-assigned animals (mean pair difference 33 mm(3) , P = 0·33). The amount of hemorrhagic transformation between the helicopter and ground groups was 4·08 vs. 4·56 μl, respectively (paired t-test, P = 0·45). This study shows that helicopter emergency medical services do not have an inherent adverse effect on outcome in a mouse model of ischemic stroke with reperfusion. These results endorse the safety of the practice of using helicopter emergency medical services in stroke patients. The observed potential synergistic effect of helicopter-induced factors, such as vibration and changes in altitude, with reperfusion merits further exploration in animal experimental models and in stroke patients. © 2015 World Stroke Organization.

Hemorrhagic Stroke in a Young Healthy Male Following Use of Pre-Workout Supplement Animal Rage XL.

Science.gov (United States)

Harris, Brandon F; Winn, Coty; Ableman, Thomas B

2017-09-01

So-called "pre-workout" supplements are substances marketed as natural dietary supplements with claims of helping athletes achieve more focused and intense workouts. The use of such products remains popular among American youth as a whole, but is especially high among active duty service members. Supplements are minimally regulated by the Food and Drug Administration (FDA), and unlike pharmaceuticals, supplements are often brought to market without any testing to show neither efficacy nor safety. Several case reports have documented serious adverse events and raise the question of whether supplement use was a causative factor. Reported events occurring after use of pre-workout supplements include, among others, ischemic stroke, hemorrhagic stroke, myocardial infarction, hepatitis, and death. Here, we present the case of a healthy 25-year-old active duty male who experienced a bilateral cerebellar hemorrhagic stroke occurring shortly after taking a supplement named Animal Rage XL. Hemorrhagic stroke occurring in a healthy 25-year-old male with no risk factors is exceedingly rare. This is the first known case of stroke temporally associated with this particular supplement, which is currently available for purchase at military exchanges. Additionally, several of the active ingredients in this supplement have been shown to cause hypertension, tachycardia, and vasospasm. All of these effects could increase the likelihood and severity of a hemorrhagic stroke. The investigated ingredients in this abstract include β-phenethylamine, creatine-monophosphate, and caffeine. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Intravenous grafts of amniotic fluid-derived stem cells induce endogenous cell proliferation and attenuate behavioral deficits in ischemic stroke rats.

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Naoki Tajiri

Full Text Available We recently reported isolation of viable rat amniotic fluid-derived stem (AFS cells [1]. Here, we tested the therapeutic benefits of AFS cells in a rodent model of ischemic stroke. Adult male Sprague-Dawley rats received a 60-minute middle cerebral artery occlusion (MCAo. Thirty-five days later, animals exhibiting significant motor deficits received intravenous transplants of rat AFS cells or vehicle. At days 60-63 post-MCAo, significant recovery of motor and cognitive function was seen in stroke animals transplanted with AFS cells compared to vehicle-infused stroke animals. Infarct volume, as revealed by hematoxylin and eosin (H&E staining, was significantly reduced, coupled with significant increments in the cell proliferation marker, Ki67, and the neuronal marker, MAP2, in the dentate gyrus (DG [2] and the subventricular zone (SVZ of AFS cell-transplanted stroke animals compared to vehicle-infused stroke animals. A significantly higher number of double-labeled Ki67/MAP2-positive cells and a similar trend towards increased Ki67/MAP2 double-labeling were observed in the DG and SVZ of AFS cell-transplanted stroke animals, respectively, compared to vehicle-infused stroke animals. This study reports the therapeutic potential of AFS cell transplantation in stroke animals, possibly via enhancement of endogenous repair mechanisms.

Risk of bias reporting in the recent animal focalcerebral ischaemia literature

DEFF Research Database (Denmark)

Bahor, Zsanett; Liao, Jing; Macleod, Malcolm

2017-01-01

Background: Findings from in vivo research may be less reliable where studies do not re-port measures to reduce risks of bias. The experimental stroke community has been at the forefront of implementing changes to improve reporting, but it is not known whether these efforts are associated...... analytic approaches to automatically ascertain re-porting of measures to reduce risk of bias from full-text articles describing animal experi-ments inducing middle cerebral artery occlusion (MCAO) or modelling lacunar stroke.Results: Compared with previous assessments, there were improvements...... was 67% (randomization), 91% (blinding) and 96% (sample size calculation).Discussion: There remains substantial opportunity for improvement in the reporting of an-imal research modelling stroke, particularly in the lacunar stroke literature. Further, auto-mated tools perform sufficiently well to identify...

Post-stroke angiotensin II type 2 receptor activation provides long-term neuroprotection in aged rats

DEFF Research Database (Denmark)

Bennion, Douglas M; Isenberg, Jacob D; Harmel, Allison T

2017-01-01

Activation of the angiotensin II type 2 receptor (AT2R) by administration of Compound 21 (C21), a selective AT2R agonist, induces neuroprotection in models of ischemic stroke in young adult animals. The mechanisms of this neuroprotective action are varied, and may include direct and indirect....... These findings demonstrate that the neuroprotection previously characterized only during earlier time points using stroke models in young animals is sustained long-term in aged rats, implying even greater clinical relevance for the study of AT2R agonists for the acute treatment of ischemic stroke in human....... Intraperitoneal injections of C21 (0.03mg/kg) after ischemic stroke induced by transient monofilament middle cerebral artery occlusion resulted in protective effects that were sustained for up to at least 3-weeks post-stroke. These included improved neurological function across multiple assessments...

Animal models

DEFF Research Database (Denmark)

Gøtze, Jens Peter; Krentz, Andrew

2014-01-01

In this issue of Cardiovascular Endocrinology, we are proud to present a broad and dedicated spectrum of reviews on animal models in cardiovascular disease. The reviews cover most aspects of animal models in science from basic differences and similarities between small animals and the human...

Modeling Dynamic Regulatory Processes in Stroke

Science.gov (United States)

McDermott, Jason E.; Jarman, Kenneth; Taylor, Ronald; Lancaster, Mary; Shankaran, Harish; Vartanian, Keri B.; Stevens, Susan L.; Stenzel-Poore, Mary P.; Sanfilippo, Antonio

2012-01-01

The ability to examine the behavior of biological systems in silico has the potential to greatly accelerate the pace of discovery in diseases, such as stroke, where in vivo analysis is time intensive and costly. In this paper we describe an approach for in silico examination of responses of the blood transcriptome to neuroprotective agents and subsequent stroke through the development of dynamic models of the regulatory processes observed in the experimental gene expression data. First, we identified functional gene clusters from these data. Next, we derived ordinary differential equations (ODEs) from the data relating these functional clusters to each other in terms of their regulatory influence on one another. Dynamic models were developed by coupling these ODEs into a model that simulates the expression of regulated functional clusters. By changing the magnitude of gene expression in the initial input state it was possible to assess the behavior of the networks through time under varying conditions since the dynamic model only requires an initial starting state, and does not require measurement of regulatory influences at each time point in order to make accurate predictions. We discuss the implications of our models on neuroprotection in stroke, explore the limitations of the approach, and report that an optimized dynamic model can provide accurate predictions of overall system behavior under several different neuroprotective paradigms. PMID:23071432

Non-Photorealistic Rendering in Chinese Painting of Animals

Institute of Scientific and Technical Information of China (English)

无

2002-01-01

A set of algorithms is proposed in this paper to automatically transform 3D animal models to Chinese painting style. Inspired by real painting process in Chinese painting of animals, we divide the whole rendering process into two parts: borderline stroke making and interior shading. In borderline stroke making process we first find 3D model silhouettes in real-time depending on the viewing direction of a user. After retrieving silhouette information from all model edges, a stroke linking mechanism is applied to link these independent edges into a long stroke. Finally we grow a plain thin silhouette line to a stylus stroke with various widths at each control point and a 2D brush model is combined with it to simulate a Chinese painting stroke. In the interior shading pipeline, three stages are used to convert a Gouraud-shading image to a Chinese painting style image: color quantization, ink diffusion and box filtering. The color quantization stage assigns all pixels in an image into four color levels and each level represents a color layer in a Chinese painting. Ink diffusion stage is used to transfer inks and water between different levels and to grow areas in an irregular way. The box filtering stage blurs sharp borders between different levels to embellish the appearance of final interior shading image. In addition to automatic rendering, an interactive Chinese painting system which is equipped with friendly input devices can be also combined to generate more artistic Chinese painting images manually.

Stem cell-like dog placenta cells afford neuroprotection against ischemic stroke model via heat shock protein upregulation.

Directory of Open Access Journals (Sweden)

Seongjin Yu

Full Text Available In this study, we investigated the dog placenta as a viable source of stem cells for stroke therapy. Immunocytochemical evaluation of phenotypic markers of dog placenta cells (DPCs cultured in proliferation and differentiation medium revealed that DPCs expressed both stem cell and neural cell markers, respectively. Co-culture with DPCs afforded neuroprotection of rat primary neural cells in a dose-dependent manner against oxygen-glucose deprivation. Subsequent in vivo experiments showed that transplantation of DPCs, in particular intravenous and intracerebral cell delivery, produced significant behavioral recovery and reduced histological deficits in ischemic stroke animals compared to those that received intra-arterial delivery of DPCs or control stroke animals. Furthermore, both in vitro and in vivo studies implicated elevated expression of heat shock protein 27 (Hsp27 as a potential mechanism of action underlying the observed therapeutic benefits of DPCs in stroke. This study supports the use of stem cells for stroke therapy and implicates a key role of Hsp27 signaling pathway in neuroprotection.

Spontaneous Reperfusion after In Situ Thromboembolic Stroke in Mice

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Cho, Tae-Hee; Bolbos, Radu; Langlois, Jean-Baptiste; Hermitte, Laure; Wiart, Marlène; Berthezène, Yves; Nighoghossian, Norbert

2012-01-01

Injection of thrombin into the middle cerebral artery (MCA) of mice has been proposed as a new model of thromboembolic stroke. The present study used sequential multiparametric Magnetic Resonance Imaging (MRI), including Magnetic Resonance Angiography (MRA), Diffusion-Weighted Imaging (DWI) and Perfusion-Weighted Imaging (PWI), to document MCA occlusion, PWI-DWI mismatch, and lesion development. In the first experiment, complete MCA occlusion and reproducible hypoperfusion were obtained in 85% of animals during the first hour after stroke onset. In the second experiment, 80% of animals showed partial to complete reperfusion during a three-hour follow-up. Spontaneous reperfusion thus contributed to the variability in ischemic volume in this model. The study confirmed the value of the model for evaluating new thrombolytic treatments, but calls for extended MRI follow-up at the acute stage in therapeutic studies. PMID:23166825

Hypertension and experimental stroke therapies

OpenAIRE

O'Collins, Victoria E; Donnan, Geoffrey A; Macleod, Malcolm R; Howells, David W

2013-01-01

Hypertension is an established target for long-term stroke prevention but procedures for management of hypertension in acute stroke are less certain. Here, we analyze basic science data to examine the impact of hypertension on candidate stroke therapies and of anti-hypertensive treatments on stroke outcome. Methods: Data were pooled from 3,288 acute ischemic stroke experiments (47,899 animals) testing the effect of therapies on infarct size (published 1978–2010). Data were combined using meta...

Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

Science.gov (United States)

Hu, Heng; Doll, Danielle N.; Sun, Jiahong; Lewis, Sara E.; Wimsatt, Jeffrey H.; Kessler, Matthew J.; Simpkins, James W.; Ren, Xuefang

2016-01-01

Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for

Potential therapeutic and protective effect of curcumin against stroke in the male albino stroke-induced model rats.

Science.gov (United States)

Zhang, Yuanyuan; Yan, Yi; Cao, Yi; Yang, Yongtao; Zhao, Qing; Jing, Rui; Hu, Jiayi; Bao, Juan

2017-08-15

The present study was carried out to understand the therapeutic effect of curcumin (CUR) against stroke in the experimental animal model. The study investigates the healing effect of CUR on mitochondrial dysfunction and inflammation. Male albino, Wistar strain rats were used for the induction of middle cerebral artery occlusion (MCAO), and reperfusion. Enzyme-linked immunosorbent assay (ELISA) was used for the determination of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the brain region. Western blot analysis was used to determine the protein expression levels of Bax, Bcl-2, p53, and Sirt1. The water level was determined in brain region by using standard method. Experimental results indicated that the use of CUR significantly reduced brain edema and water content. IL-6 and TNF-α were significantly reduced in the brain region following use of CUR. Mitochondrial membrane potential (MMP) also reduced significantly after CUR treatment. Protein expression of p53 and Bax were significantly reduced, whereas Bcl-2 and Sirt1 were increased following CUR treatment. Taking all these data together, it is suggested that the use of CUR may be a potential therapeutic agent for the treatment of stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

A systematic review and meta-analysis of the efficacy of piracetam and piracetam-like compounds in experimental stroke.

Science.gov (United States)

Wheble, Philippa C R; Sena, Emily S; Macleod, Malcolm R

2008-01-01

Piracetam was a candidate neuroprotective drug for acute stroke ineffective in clinical trial. Here we use systematic review and meta-analysis to describe the evidence supporting a protective effect of piracetam and its derivatives in animal models of stroke. We present a systematic review of reports describing the use of piracetam and its derivatives in animal models of focal ischaemia, where the outcome was measured as an infarct size or neurological score (Der Simonian and Laird random effects meta-analysis). Only 2 studies, published 10 years after the first clinical trial of piracetam had been initiated, described its efficacy in animal models of stroke. A further 4 studies described the efficacy of related compounds. Piracetam and its derivatives improved the outcome by 30.2% (95% CI = 16.1-44.4). The median study quality was 4/10 (inter-quartile range = 4-6). Piracetam and its derivatives demonstrate neuroprotective efficacy in experimental stroke, but our findings raise concerns about the amount of available data, the quality of the studies and publication bias. (c) 2007 S. Karger AG, Basel.

Impact of Stroke Therapy Academic Industry Roundtable (STAIR Guidelines on Peri-Anesthesia Care for Rat Models of Stroke: A Meta-Analysis Comparing the Years 2005 and 2015.

Directory of Open Access Journals (Sweden)

Aurelie Thomas

Full Text Available Numerous studies using rats in stroke models have failed to translate into successful clinical trials in humans. The Stroke Therapy Academic Industry Roundtable (STAIR has produced guidelines on the rodent stroke model for preclinical trials in order to promote the successful translation of animal to human studies. These guidelines also underline the importance of anaesthetic and monitoring techniques. The aim of this literature review is to document whether anaesthesia protocols (i.e., choice of agents, mode of ventilation, physiological support and monitoring have been amended since the publication of the STAIR guidelines in 2009. A number of articles describing the use of a stroke model in adult rats from the years 2005 and 2015 were randomly selected from the PubMed database and analysed for the following parameters: country where the study was performed, strain of rats used, technique of stroke induction, anaesthetic agent for induction and maintenance, mode of intubation and ventilation, monitoring techniques, control of body temperature, vascular accesses, and administration of intravenous fluids and analgesics. For each parameter (stroke, induction, maintenance, monitoring, exact chi-square tests were used to determine whether or not proportions were significantly different across year and p values were corrected for multiple comparisons. An exact p-test was used for each parameter to compare the frequency distribution of each value followed by a Bonferroni test. The level of significant set at < 0.05. Results show that there were very few differences in the anaesthetic and monitoring techniques used between 2005 and 2015. In 2015, significantly more studies were performed in China and significantly fewer studies used isoflurane and nitrous oxide. The most striking finding is that the vast majority of all the studies from both 2005 and 2015 did not report the use of ventilation; measurement of blood gases, end-tidal carbon dioxide

Drug-induced Hypothermia by 5HT1A Agonists Provide Neuroprotection in Experimental Stroke

DEFF Research Database (Denmark)

Johansen, Flemming Fryd; Hasseldam, Henrik; Nybro Smith, Matthias

2014-01-01

BACKGROUND: Drug-induced hypothermia reduces brain damage in animal stroke models and is an undiscovered potential in human stroke treatment. We studied hypothermia induced by the serotonergic agonists S14671 (1-[2-(2-thenoylamino)ethyl]-4[1-(7- methoxynaphtyl)]piperazine) and ipsapirone in a rat...... therapeutic hypothermia....

Recent Advances in Stem Cell-Based Therapeutics for Stroke

OpenAIRE

Napoli, Eleonora; Borlongan, Cesar V.

2016-01-01

Regenerative medicine for central nervous system disorders, including stroke, has challenged the non-regenerative capacity of the brain. Among the many treatment strategies tailored towards repairing the injured brain, stem cell-based therapeutics have been demonstrated as safe and effective in animal models of stroke, and are being tested in limited clinical trials. We address here key lab-to-clinic translational research that relate to efficacy, safety, and mechanism of action underlying st...

Stimulation of the sphenopalatine ganglion induces reperfusion and blood-brain barrier protection in the photothrombotic stroke model.

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Haviv Levi

Full Text Available The treatment of stroke remains a challenge. Animal studies showing that electrical stimulation of the sphenopalatine ganglion (SPG exerts beneficial effects in the treatment of stroke have led to the initiation of clinical studies. However, the detailed effects of SPG stimulation on the injured brain are not known.The effect of acute SPG stimulation was studied by direct vascular imaging, fluorescent angiography and laser Doppler flowmetry in the sensory motor cortex of the anaesthetized rat. Focal cerebral ischemia was induced by the rose bengal (RB photothrombosis method. In chronic experiments, SPG stimulation, starting 15 min or 24 h after photothrombosis, was given for 3 h per day on four consecutive days. Structural damage was assessed using histological and immunohistochemical methods. Cortical functions were assessed by quantitative analysis of epidural electro-corticographic (ECoG activity continuously recorded in behaving animals.Stimulation induced intensity- and duration-dependent vasodilation and increased cerebral blood flow in both healthy and photothrombotic brains. In SPG-stimulated rats both blood brain-barrier (BBB opening, pathological brain activity and lesion volume were attenuated compared to untreated stroke animals, with no apparent difference in the glial response surrounding the necrotic lesion.SPG-stimulation in rats induces vasodilation of cortical arterioles, partial reperfusion of the ischemic lesion, and normalization of brain functions with reduced BBB dysfunction and stroke volume. These findings support the potential therapeutic effect of SPG stimulation in focal cerebral ischemia even when applied 24 h after stroke onset and thus may extend the therapeutic window of currently administered stroke medications.

Efficacy of Alteplase® in a mouse model of acute ischemic stroke: a retrospective pooled analysis

Science.gov (United States)

Orset, Cyrille; Haelewyn, Benoit; Allan, Stuart M.; Ansar, Saema; Campos, Francesco; Cho, Tae Hee; Durand, Anne; El Amki, Mohamad; Fatar, Marc; Garcia-Yébenes, Isaac; Gauberti, Maxime; Grudzenski, Saskia; Lizasoain, Ignacio; Lo, Eng; Macrez, Richard; Margaill, Isabelle; Maysami, Samaneh; Meairs, Stephen; Nighoghossian, Norbert; Orbe, Josune; Paramo, Jose Antonio; Parienti, Jean-Jacques; Rothwell, Nancy J.; Rubio, Marina; Waeber, Christian; Young, Alan R.

2016-01-01

Background and purpose The debate over the fact that experimental drugs proposed for the treatment of stroke fail in the translation to the clinical situation, has attracted considerable attention in the literature. In this context, we present a retrospective pooled analysis of a large dataset from pre-clinical studies, in order to examine the effects of early versus late administration of intravenous recombinant tissue type plasminogen activator (rt-PA). Methods We collected data from 26 individual studies from 9 international centers (13 researchers, 716 animals) that compared rt-PA to controls, in a unique mouse model of thromboembolic stroke induced by an in situ injection of thrombin into the middle cerebral artery. Studies were classified into early (<3h) versus late (≥3h) drug administration. Final infarct volumes, assessed by histology or MRI, were compared in each study and the absolute differences were pooled in a random-effect meta-analysis. The influence of time of administration was tested. Results When compared to saline controls, early rt-PA administration was associated with a significant benefit (absolute difference = −6.63 mm3; 95%CI, −9.08 to −4.17; I2=76%) whereas late rt-PA treatment showed a deleterious effect (+5.06 mm3; 95%CI, +2.78 to +7.34; I2=42%, Pint<0.00001). Results remained unchanged following subgroup analyses. Conclusion Our results provide the basis needed for the design of future pre-clinical studies on recanalization therapies using this model of thromboembolic stroke in mice. The power analysis reveals that a multi-center trial would require 123 animals per group instead of 40 for a single center trial. PMID:27032444

Thrombotic stroke in the anesthetized monkey (Macaca mulatta): characterization by MRI - A pilot study

International Nuclear Information System (INIS)

Gauberti, Maxime; Gakuba, Clement; Orset, Cyrille; Obiang, Pauline; Guedin, Pierre; Balossier, Anne; Diependaele, Anne-Sophie; Young, Alan R.; Agin, Veronique; Chazalviel, Laurent; Vivien, Denis

2012-01-01

The lack of a relevant stroke model in large nonhuman primates hinders the development of innovative diagnostic/therapeutic approaches concerned with this cerebrovascular disease. Our objective was to develop a novel and clinically relevant model of embolic stroke in the anesthetized monkey that incorporates readily available clinical imaging techniques and that would allow the possibility of drug delivery including strategies of reperfusion. Thrombin was injected into the lumen of the middle cerebral artery (MCA) in 12 anesthetized (sevoflurane) male rhesus macaques (Macaca mulatta). Sequential MRI studies (including angiography, FLAIR, PWI, DWI, and gadolinium-enhanced T1W imaging) were performed in a 3 T clinical MRI. Physiological and biochemical parameters were monitored throughout the investigations. Once standardized, the surgical procedure induced transient occlusion of the middle cerebral artery in all operated animals. All animals studied showed spontaneous reperfusion, which occurred some time between 2 h and 7 days post-ictus. Eighty percent of the studied animals showed diffusion/perfusion mismatch. The ischemic lesions at 24 h spared both superficial and profound territories of the MCA. Some animals presented hemorrhagic transformation at 7 days post-ictus. In this study, we developed a pre-clinically relevant model of embolic stroke in the anesthetized nonhuman primate. (authors)

Scalp acupuncture attenuates neurological deficits in a rat model of hemorrhagic stroke.

Science.gov (United States)

Liu, Hao; Sun, Xiaowei; Zou, Wei; Leng, Mengtong; Zhang, Beng; Kang, Xiaoyu; He, Tao; Wang, Hui

2017-06-01

Hemorrhagic stroke accounts for approximately 15% of all stroke cases, and is associated with high morbidity and mortality. Limited human studies suggested that scalp acupuncture could facilitate functional recovery after cerebral hemorrhage. In the current study, we used an animal model of cerebral hemorrhage to examine the potential effects of scalp acupuncture. Adult male Sprague-Dawley rats received autologous blood (50μL) into the right caudate nucleus on the right side under pentobarbital anesthesia, and then received scalp acupuncture (DU20 through GB7 on the lesion side) or sham acupuncture (1cm to the right side of the acupoints) (n=10 per group). A group of rats receiving autologous blood into the caudate nucleus but no other intervention, as well as a group of rats receiving anesthesia but no blood injection to the brain (n=10 per group) were included as additional controls. Composite neuroscore, corner turn test, forelimb placing test, wire hang task and beam walking were used to evaluate the behavior of rats. Hematoxylin and Eosin (HE) staining was used to observe the histopathological changes. Western blot was used to detect the content of tumor necrosis factor alpha (TNF-α) and nuclear factor-KappaB (NFκB) protein expression. Scalp acupuncture attenuated neurological deficits (phemorrhagic stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.

The WZNW model on PSU(1, 1 vertical stroke 2)

International Nuclear Information System (INIS)

Goetz, G.

2006-10-01

According to the work of Berkovits, Vafa and Witten, the non-linear sigma model on the supergroup PSU(1,1 vertical stroke 2) is the essential building block for string theory on AdS 3 xS 3 xT 4 . Models associated with a non-vanishing value of the RR flux can be obtained through a psu(1,1 vertical stroke 2) invariant marginal deformation of the WZNW model on PSU(1,1 vertical stroke 2). We take this as a motivation to present a manifestly psu(1,1 vertical stroke 2) covariant construction of the model at the Wess-Zumino point, corresponding to a purely NSNS background 3-form flux. At this point the model possesses an enhanced psu(1,1 vertical stroke 2) current algebra symmetry whose representation theory, including explicit character formulas, is developed systematically in the first part of the paper. The space of vertex operators and a free fermion representation for their correlation functions is our main subject in the second part. Contrary to a widespread claim, bosonic and fermionic fields are necessarily coupled to each other. The interaction changes the supersymmetry transformations, with drastic consequences for the multiplets of localized normalizable states in the model. It is only this fact which allows us to decompose the full state space into multiplets of the global supersymmetry. We analyze these decompositions systematically as a preparation for a forthcoming study of the RR deformation. (orig.)

The WZNW model on PSU(1, 1 vertical stroke 2)

Energy Technology Data Exchange (ETDEWEB)

Goetz, G. [CEA Centre d' Etudes de Saclay, 91 - Gif-sur-Yvette (France). Service de Physique Theorique; Quella, T. [King' s College London (United Kingdom). Dept. of Mathematics]|[Amsterdam Univ. (Netherlands). KdV Institute for Mathematics; Schomerus, V. [CEA Centre d' Etudes de Saclay, 91 - Gif-sur-Yvette (France). Service de Physique Theorique]|[Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

2006-10-15

According to the work of Berkovits, Vafa and Witten, the non-linear sigma model on the supergroup PSU(1,1 vertical stroke 2) is the essential building block for string theory on AdS{sub 3}xS{sup 3}xT{sup 4}. Models associated with a non-vanishing value of the RR flux can be obtained through a psu(1,1 vertical stroke 2) invariant marginal deformation of the WZNW model on PSU(1,1 vertical stroke 2). We take this as a motivation to present a manifestly psu(1,1 vertical stroke 2) covariant construction of the model at the Wess-Zumino point, corresponding to a purely NSNS background 3-form flux. At this point the model possesses an enhanced psu(1,1 vertical stroke 2) current algebra symmetry whose representation theory, including explicit character formulas, is developed systematically in the first part of the paper. The space of vertex operators and a free fermion representation for their correlation functions is our main subject in the second part. Contrary to a widespread claim, bosonic and fermionic fields are necessarily coupled to each other. The interaction changes the supersymmetry transformations, with drastic consequences for the multiplets of localized normalizable states in the model. It is only this fact which allows us to decompose the full state space into multiplets of the global supersymmetry. We analyze these decompositions systematically as a preparation for a forthcoming study of the RR deformation. (orig.)

Modulation of brain plasticity in stroke: a novel model for neurorehabilitation.

Science.gov (United States)

Di Pino, Giovanni; Pellegrino, Giovanni; Assenza, Giovanni; Capone, Fioravante; Ferreri, Florinda; Formica, Domenico; Ranieri, Federico; Tombini, Mario; Ziemann, Ulf; Rothwell, John C; Di Lazzaro, Vincenzo

2014-10-01

Noninvasive brain stimulation (NIBS) techniques can be used to monitor and modulate the excitability of intracortical neuronal circuits. Long periods of cortical stimulation can produce lasting effects on brain function, paving the way for therapeutic applications of NIBS in chronic neurological disease. The potential of NIBS in stroke rehabilitation has been of particular interest, because stroke is the main cause of permanent disability in industrial nations, and treatment outcomes often fail to meet the expectations of patients. Despite promising reports from many clinical trials on NIBS for stroke recovery, the number of studies reporting a null effect remains a concern. One possible explanation is that the interhemispheric competition model--which posits that suppressing the excitability of the hemisphere not affected by stroke will enhance recovery by reducing interhemispheric inhibition of the stroke hemisphere, and forms the rationale for many studies--is oversimplified or even incorrect. Here, we critically review the proposed mechanisms of synaptic and functional reorganization after stroke, and suggest a bimodal balance-recovery model that links interhemispheric balancing and functional recovery to the structural reserve spared by the lesion. The proposed model could enable NIBS to be tailored to the needs of individual patients.

A Unified Model of Cloud-to-Ground Lightning Stroke

Science.gov (United States)

Nag, A.; Rakov, V. A.

2014-12-01

The first stroke in a cloud-to-ground lightning discharge is thought to follow (or be initiated by) the preliminary breakdown process which often produces a train of relatively large microsecond-scale electric field pulses. This process is poorly understood and rarely modeled. Each lightning stroke is composed of a downward leader process and an upward return-stroke process, which are usually modeled separately. We present a unified engineering model for computing the electric field produced by a sequence of preliminary breakdown, stepped leader, and return stroke processes, serving to transport negative charge to ground. We assume that a negatively-charged channel extends downward in a stepped fashion through the relatively-high-field region between the main negative and lower positive charge centers and then through the relatively-low-field region below the lower positive charge center. A relatively-high-field region is also assumed to exist near ground. The preliminary breakdown pulse train is assumed to be generated when the negatively-charged channel interacts with the lower positive charge region. At each step, an equivalent current source is activated at the lower extremity of the channel, resulting in a step current wave that propagates upward along the channel. The leader deposits net negative charge onto the channel. Once the stepped leader attaches to ground (upward connecting leader is presently neglected), an upward-propagating return stroke is initiated, which neutralizes the charge deposited by the leader along the channel. We examine the effect of various model parameters, such as step length and current propagation speed, on model-predicted electric fields. We also compare the computed fields with pertinent measurements available in the literature.

Branes in the GL(1 vertical stroke 1) WZNW-Model

Energy Technology Data Exchange (ETDEWEB)

Creutzig, T.; Schomerus, V. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Quella, T. [Amsterdam Univ. (Netherlands). KdV Inst. for Mathematics

2007-08-15

We initiate a systematic study of boundary conditions in conformal field theories with target space supersymmetry. The WZNW model on GL(1 vertical stroke 1) is used as a prototypical example for which we find the complete set of maximally symmetric branes. This includes a unique brane of maximal super-dimension 2 vertical stroke 2, a 2-parameter family of branes with super-dimension 0 vertical stroke 2 and an infinite set of fully localized branes possessing a single modulus. Members of the latter family can only exist along certain lines on the bosonic base, much like fractional branes at orbifold singularities. Our results establish that all essential algebraic features of Cardy-type boundary theories carry over to the non-rational logarithmic WZNW model on GL(1 vertical stroke 1). (orig.)

Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling

DEFF Research Database (Denmark)

Kammersgaard, L P; Rasmussen, B H; Jørgensen, Henrik Stig

2000-01-01

Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients...

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

Science.gov (United States)

Zhan, Xianbao; Wang, Fan; Bi, Yan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.

Science.gov (United States)

Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

2016-09-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. Copyright © 2016 the American Physiological Society.

Post-stroke angiotensin II type 2 receptor activation provides long-term neuroprotection in aged rats.

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Douglas M Bennion

Full Text Available Activation of the angiotensin II type 2 receptor (AT2R by administration of Compound 21 (C21, a selective AT2R agonist, induces neuroprotection in models of ischemic stroke in young adult animals. The mechanisms of this neuroprotective action are varied, and may include direct and indirect effects of AT2R activation. Our objectives were to assess the long-term protective effects of post-stroke C21 treatments in a clinically-relevant model of stroke in aged rats and to characterize the cellular localization of AT2Rs in the mouse brain of transgenic reporter mice following stroke. Intraperitoneal injections of C21 (0.03mg/kg after ischemic stroke induced by transient monofilament middle cerebral artery occlusion resulted in protective effects that were sustained for up to at least 3-weeks post-stroke. These included improved neurological function across multiple assessments and a significant reduction in infarct volume as assessed by magnetic resonance imaging. We also found AT2R expression to be on neurons, not astrocytes or microglia, in normal female and male mouse brains. Stroke did not induce altered cellular localization of AT2R when assessed at 7 and 14 days post-stroke. These findings demonstrate that the neuroprotection previously characterized only during earlier time points using stroke models in young animals is sustained long-term in aged rats, implying even greater clinical relevance for the study of AT2R agonists for the acute treatment of ischemic stroke in human disease. Further, it appears that this sustained neuroprotection is likely due to a mix of both direct and indirect effects stemming from selective activation of AT2Rs on neurons or other cells besides astrocytes and microglia.

Post-stroke angiotensin II type 2 receptor activation provides long-term neuroprotection in aged rats.

Science.gov (United States)

Bennion, Douglas M; Isenberg, Jacob D; Harmel, Allison T; DeMars, Kelly; Dang, Alex N; Jones, Chad H; Pignataro, Megan E; Graham, Justin T; Steckelings, U Muscha; Alexander, Jon C; Febo, Marcelo; Krause, Eric G; de Kloet, Annette D; Candelario-Jalil, Eduardo; Sumners, Colin

2017-01-01

Activation of the angiotensin II type 2 receptor (AT2R) by administration of Compound 21 (C21), a selective AT2R agonist, induces neuroprotection in models of ischemic stroke in young adult animals. The mechanisms of this neuroprotective action are varied, and may include direct and indirect effects of AT2R activation. Our objectives were to assess the long-term protective effects of post-stroke C21 treatments in a clinically-relevant model of stroke in aged rats and to characterize the cellular localization of AT2Rs in the mouse brain of transgenic reporter mice following stroke. Intraperitoneal injections of C21 (0.03mg/kg) after ischemic stroke induced by transient monofilament middle cerebral artery occlusion resulted in protective effects that were sustained for up to at least 3-weeks post-stroke. These included improved neurological function across multiple assessments and a significant reduction in infarct volume as assessed by magnetic resonance imaging. We also found AT2R expression to be on neurons, not astrocytes or microglia, in normal female and male mouse brains. Stroke did not induce altered cellular localization of AT2R when assessed at 7 and 14 days post-stroke. These findings demonstrate that the neuroprotection previously characterized only during earlier time points using stroke models in young animals is sustained long-term in aged rats, implying even greater clinical relevance for the study of AT2R agonists for the acute treatment of ischemic stroke in human disease. Further, it appears that this sustained neuroprotection is likely due to a mix of both direct and indirect effects stemming from selective activation of AT2Rs on neurons or other cells besides astrocytes and microglia.

Developing and Validating a Predictive Model for Stroke Progression

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L.E. Craig

2011-12-01

Full Text Available Background: Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Methods: Two patient cohorts were used for this study – the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863 was used to develop the model. Variables that were statistically significant (p 0.1 in turn. The second cohort (n = 216 was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Results: Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72–0.73] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50–0.92]. Conclusion: The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the

Developing and validating a predictive model for stroke progression.

Science.gov (United States)

Craig, L E; Wu, O; Gilmour, H; Barber, M; Langhorne, P

2011-01-01

Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Two patient cohorts were used for this study - the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863) was used to develop the model. Variables that were statistically significant (p p > 0.1) in turn. The second cohort (n = 216) was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72-0.73)] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50-0.92)]. The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the discrimination and calibration of the predictive model appear

Developing and Validating a Predictive Model for Stroke Progression

Science.gov (United States)

Craig, L.E.; Wu, O.; Gilmour, H.; Barber, M.; Langhorne, P.

2011-01-01

Background Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Methods Two patient cohorts were used for this study – the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863) was used to develop the model. Variables that were statistically significant (p 0.1) in turn. The second cohort (n = 216) was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Results Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72–0.73)] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50–0.92)]. Conclusion The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the discrimination and

Logical Analysis of Data (LAD model for the early diagnosis of acute ischemic stroke

Directory of Open Access Journals (Sweden)

Hoehn Gerard

2008-07-01

Full Text Available Abstract Background Strokes are a leading cause of morbidity and the first cause of adult disability in the United States. Currently, no biomarkers are being used clinically to diagnose acute ischemic stroke. A diagnostic test using a blood sample from a patient would potentially be beneficial in treating the disease. Results A classification approach is described for differentiating between proteomic samples of stroke patients and controls, and a second novel predictive model is developed for predicting the severity of stroke as measured by the National Institutes of Health Stroke Scale (NIHSS. The models were constructed by applying the Logical Analysis of Data (LAD methodology to the mass peak profiles of 48 stroke patients and 32 controls. The classification model was shown to have an accuracy of 75% when tested on an independent validation set of 35 stroke patients and 25 controls, while the predictive model exhibited superior performance when compared to alternative algorithms. In spite of their high accuracy, both models are extremely simple and were developed using a common set consisting of only 3 peaks. Conclusion We have successfully identified 3 biomarkers that can detect ischemic stroke with an accuracy of 75%. The performance of the classification model on the validation set and on cross-validation does not deteriorate significantly when compared to that on the training set, indicating the robustness of the model. As in the case of the LAD classification model, the results of the predictive model validate the function constructed on our support-set for approximating the severity scores of stroke patients. The correlation and root mean absolute error of the LAD predictive model are consistently superior to those of the other algorithms used (Support vector machines, C4.5 decision trees, Logistic regression and Multilayer perceptron.

UCAO (UNILATERAL CEREBRAL ARTERY OCCLUSSION METHOD INCREASES THE LEVEL OF MMP- 9 BRAIN TISSUE IN RATS MODEL OF ISCHEMIC STROKE

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M. Rasjad Indra

2016-07-01

Full Text Available Background. For the last 5 years, 15.4% of total population died because of stroke, which 42.9% of those are caused by ischemic stroke. UCAO (Unilateral Cerebral Artery Occlusion is a stroke induction method by ligating mice’s carotid artery for 45 minutes. Thus, giving a hypoxic condition similar to stroke attack in human. This method is less complicated and far more efficient. MMP-9 is a stroke marker which is assayed by ELISA from the blood of test animal. Objective. This research was conducted to prove UCAO (Unilateral Cerebral Artery Occlusion method is capable to raise MMP-9 concentration in mice’s blood. Methods. This research was an experimental laboratory research with post-test only controlled group design. 8 male rats (8-10 weeks were divided into 2 groups, control and treatment which would be inducted into stroke by UCAO method. A day after the treatment group had been induced to stroke, both group were tested to measure the MMP-9 blood concentration through ELISA. Results. In this research, UCAO method had increased MMP-9 blood concentration in treatment group, compared to the control group. It is proved by the statistic tests, Mann-Whitney and Kruskal-Wallis, which showed a significant increase in treatment group (p < 0.05. Conclusion. Based on this result, it can be concluded that UCAO method is accepted as a method to create an ischemic stroke mice model.

Delivering Knowledge of Stroke to Parents Through Their Children Using a Manga for Stroke Education in Elementary School.

Science.gov (United States)

Ishigami, Akiko; Yokota, Chiaki; Nishimura, Kunihiro; Ohyama, Satoshi; Tomari, Shinya; Hino, Tenyu; Arimizu, Takuro; Wada, Shinichi; Toyoda, Kazunori; Minematsu, Kazuo

2017-02-01

School-based intervention would be promising to spread stroke knowledge widely. This study aimed to clarify the effectiveness of our new educational aids that were developed for elementary school children to impart information about stroke to children and their parents in 2 different ways: with or without stroke lessons by a neurologist. We enrolled 562 children (aged 11 to 12 years) and their parents (n = 485). The students were divided into 2 groups: 323 received a lesson on stroke by a stroke neurologist without watching an animated cartoon (Group I), and 239 watched an animated cartoon without the lesson (Group II). All of the children took the manga home, and talked about stroke with their parents. Questionnaires on stroke knowledge were administered at baseline (BL), immediately after the lesson (IL), and 3 months (3M) after the lesson. There were significant increases in the adjusted mean scores for risk factors as well as stroke symptoms at 3M in both groups compared with BL scores, although the children in Group I scored significantly better than those in Group II at IL and 3M (P < .05). In both children and parents, the correct answer rates of the FAST mnemonic at 3M were around 90%, with no significant differences between groups. Stroke education for elementary school children using our educational aids provided knowledge of stroke symptoms to the children as well as their parents even without lessons on stroke, although a better understanding of stroke was obtained from lessons led by stroke neurologists. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Experimental acute thrombotic stroke in baboons

International Nuclear Information System (INIS)

Del Zoppo, G.J.; Copeland, B.R.; Harker, L.A.; Waltz, T.A.; Zyroff, J.; Hanson, S.R.; Battenberg, E.

1986-01-01

To study the effects of antithrombotic therapy in experimental stroke, we have characterized a baboon model of acute cerebrovascular thrombosis. In this model an inflatable silastic balloon cuff has been implanted by transorbital approach around the right middle cerebral artery (MCA), proximal to the take-off of the lenticulostriate arteries (LSA). Inflation of the balloon for 3 hours in six animals produced a stereotypic sustained stroke syndrome characterized by contralateral hemiparesis. An infarction volume of 3.2 +/- 1.5 cm3 in the ipsilateral corpus striatum was documented by computerized tomographic (CT) scanning at 10 days following stroke induction and 3.9 +/- 1.9 cm3 (n = 4) at 14 days by morphometric neuropathologic determinations of brain specimens fixed in situ by pressure-perfusion with 10% buffered formalin. Immediate pressure-perfusion fixation following deflation of the balloon was performed in 16 additional animals given Evans blue dye intravenously prior to the 3 hour MCA balloon occlusion. Light microscopy and transmission electron microscopy consistently confirmed the presence of thrombotic material occluding microcirculatory branches of the right LSA in the region of Evans blue stain, but not those of the contralateral corpus striatum. When autologous 111In-platelets were infused intravenously in four animals from the above group prior to the transient 3 hour occlusion of the right MCA, gamma scintillation camera imaging of each perfused-fixed whole brain demonstrated the presence of a single residual focus of 111In-platelet activity involving only the Evans blue-stained right corpus striatum. Focal right hemispheric activity was equivalent to 0.55 +/- 0.49 ml of whole blood, and the occlusion score derived from histologic examination of the microcirculation of the Evans blue-stained corpus striatum averaged 34.8 +/- 2.8

Soetomo score: score model in early identification of acute haemorrhagic stroke

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Moh Hasan Machfoed

2016-06-01

Full Text Available Aim of the study: On financial or facility constraints of brain imaging, score model is used to predict the occurrence of acute haemorrhagic stroke. Accordingly, this study attempts to develop a new score model, called Soetomo score. Material and methods: The researchers performed a cross-sectional study of 176 acute stroke patients with onset of ≤24 hours who visited emergency unit of Dr. Soetomo Hospital from July 14th to December 14th, 2014. The diagnosis of haemorrhagic stroke was confirmed by head computed tomography scan. There were seven predictors of haemorrhagic stroke which were analysed by using bivariate and multivariate analyses. Furthermore, a multiple discriminant analysis resulted in an equation of Soetomo score model. The receiver operating characteristic procedure resulted in the values of area under curve and intersection point identifying haemorrhagic stroke. Afterward, the diagnostic test value was determined. Results: The equation of Soetomo score model was (3 × loss of consciousness + (3.5 × headache + (4 × vomiting − 4.5. Area under curve value of this score was 88.5% (95% confidence interval = 83.3–93.7%. In the Soetomo score model value of ≥−0.75, the score reached the sensitivity of 82.9%, specificity of 83%, positive predictive value of 78.8%, negative predictive value of 86.5%, positive likelihood ratio of 4.88, negative likelihood ratio of 0.21, false negative of 17.1%, false positive of 17%, and accuracy of 83%. Conclusions: The Soetomo score model value of ≥−0.75 can identify acute haemorrhagic stroke properly on the financial or facility constrains of brain imaging.

Evaluation of Gene Therapy as an Intervention Strategy to Treat Brain Injury from Stroke

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Amanda J Craig

2016-05-01

Full Text Available Stroke is a leading cause of death and disability, with a lack of treatments available to prevent cell death, regenerate damaged cells and pathways, or promote neurogenesis. The extended period of hours to weeks over which tissue damage continues to occur makes this disorder a candidate for gene therapy. This review highlights the development of gene therapy in the area of stroke, with the evolution of viral administration, in experimental stroke models, from pre-injury to clinically relevant timeframes of hours to days post-stroke. The putative therapeutic proteins being examined include anti-apoptotic, pro-survival, anti-inflammatory, and guidance proteins, targeting multiple pathways within the complex pathology, with promising results. The balance of findings from animal models suggests that gene therapy provides a viable translational platform for treatment of ischaemic brain injury arising from stroke.

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

OpenAIRE

Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mai...

Animal models of dementia

DEFF Research Database (Denmark)

Olsson, I. Anna S.; Sandøe, Peter

2011-01-01

This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches...... are here distinguished. These serve as points of orientation in the following discussion of four more specific ethical questions: Does animal species matter? How effective is disease modelling in delivering the benefits claimed for it? What can be done to minimize potential harm to animals in research? Who...... bears responsibility for the use of animals in disease models?...

Development and Validation of a Predictive Model for Functional Outcome After Stroke Rehabilitation: The Maugeri Model.

Science.gov (United States)

Scrutinio, Domenico; Lanzillo, Bernardo; Guida, Pietro; Mastropasqua, Filippo; Monitillo, Vincenzo; Pusineri, Monica; Formica, Roberto; Russo, Giovanna; Guarnaschelli, Caterina; Ferretti, Chiara; Calabrese, Gianluigi

2017-12-01

Prediction of outcome after stroke rehabilitation may help clinicians in decision-making and planning rehabilitation care. We developed and validated a predictive tool to estimate the probability of achieving improvement in physical functioning (model 1) and a level of independence requiring no more than supervision (model 2) after stroke rehabilitation. The models were derived from 717 patients admitted for stroke rehabilitation. We used multivariable logistic regression analysis to build each model. Then, each model was prospectively validated in 875 patients. Model 1 included age, time from stroke occurrence to rehabilitation admission, admission motor and cognitive Functional Independence Measure scores, and neglect. Model 2 included age, male gender, time since stroke onset, and admission motor and cognitive Functional Independence Measure score. Both models demonstrated excellent discrimination. In the derivation cohort, the area under the curve was 0.883 (95% confidence intervals, 0.858-0.910) for model 1 and 0.913 (95% confidence intervals, 0.884-0.942) for model 2. The Hosmer-Lemeshow χ 2 was 4.12 ( P =0.249) and 1.20 ( P =0.754), respectively. In the validation cohort, the area under the curve was 0.866 (95% confidence intervals, 0.840-0.892) for model 1 and 0.850 (95% confidence intervals, 0.815-0.885) for model 2. The Hosmer-Lemeshow χ 2 was 8.86 ( P =0.115) and 34.50 ( P =0.001), respectively. Both improvement in physical functioning (hazard ratios, 0.43; 0.25-0.71; P =0.001) and a level of independence requiring no more than supervision (hazard ratios, 0.32; 0.14-0.68; P =0.004) were independently associated with improved 4-year survival. A calculator is freely available for download at https://goo.gl/fEAp81. This study provides researchers and clinicians with an easy-to-use, accurate, and validated predictive tool for potential application in rehabilitation research and stroke management. © 2017 American Heart Association, Inc.

Validation of simplified centre of mass models during gait in individuals with chronic stroke.

Science.gov (United States)

Huntley, Andrew H; Schinkel-Ivy, Alison; Aqui, Anthony; Mansfield, Avril

2017-10-01

The feasibility of using a multiple segment (full-body) kinematic model in clinical gait assessment is difficult when considering obstacles such as time and cost constraints. While simplified gait models have been explored in healthy individuals, no such work to date has been conducted in a stroke population. The aim of this study was to quantify the errors of simplified kinematic models for chronic stroke gait assessment. Sixteen individuals with chronic stroke (>6months), outfitted with full body kinematic markers, performed a series of gait trials. Three centre of mass models were computed: (i) 13-segment whole-body model, (ii) 3 segment head-trunk-pelvis model, and (iii) 1 segment pelvis model. Root mean squared error differences were compared between models, along with correlations to measures of stroke severity. Error differences revealed that, while both models were similar in the mediolateral direction, the head-trunk-pelvis model had less error in the anteroposterior direction and the pelvis model had less error in the vertical direction. There was some evidence that the head-trunk-pelvis model error is influenced in the mediolateral direction for individuals with more severe strokes, as a few significant correlations were observed between the head-trunk-pelvis model and measures of stroke severity. These findings demonstrate the utility and robustness of the pelvis model for clinical gait assessment in individuals with chronic stroke. Low error in the mediolateral and vertical directions is especially important when considering potential stability analyses during gait for this population, as lateral stability has been previously linked to fall risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structure constants of the OSP(1 vertical stroke 2) WZNW model

Energy Technology Data Exchange (ETDEWEB)

Hikida, Y.; Schomerus, V.

2007-11-15

We propose exact formulas for the 2- and 3-point functions of the WZNW model on the non-compact supergroup OSP(1 vertical stroke 2). Using the path integral approach that was recently developed in arXiv:0706.1030 we show how local correlation functions in the OSP(p vertical stroke 2) WZNW models can be obtained from those of N=p supersymmetric Liouville field theory for p=1,2. We then employ known results on correlators in N=1 Liouville theory to determine the structure constants of the OSP(1 vertical stroke 2) theory. (orig.)

Modelling Farm Animal Welfare

Science.gov (United States)

Collins, Lisa M.; Part, Chérie E.

2013-01-01

Simple Summary In this review paper we discuss the different modeling techniques that have been used in animal welfare research to date. We look at what questions they have been used to answer, the advantages and pitfalls of the methods, and how future research can best use these approaches to answer some of the most important upcoming questions in farm animal welfare. Abstract The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively) based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested. PMID:26487411

A unified engineering model of the first stroke in downward negative lightning

Science.gov (United States)

Nag, Amitabh; Rakov, Vladimir A.

2016-03-01

Each stroke in a negative cloud-to-ground lightning flash is composed of downward leader and upward return stroke processes, which are usually modeled individually. The first stroke leader is stepped and starts with preliminary breakdown (PB) which is often viewed as a separate process. We present the first unified engineering model for computing the electric field produced by a sequence of PB, stepped leader, and return stroke processes, serving to transport negative charge to ground. We assume that a negatively charged channel extends downward in a stepped fashion during both the PB and leader stages. Each step involves a current wave that propagates upward along the newly formed channel section. Once the leader attaches to ground, an upward propagating return stroke neutralizes the charge deposited along the channel. Model-predicted electric fields are in reasonably good agreement with simultaneous measurements at both near (hundreds of meters, electrostatic field component is dominant) and far (tens of kilometers, radiation field component is dominant) distances from the lightning channel. Relations between the features of computed electric field waveforms and model input parameters are examined. It appears that peak currents associated with PB pulses are similar to return stroke peak currents, and the observed variation of electric radiation field peaks produced by leader steps at different heights above ground is influenced by the ground corona space charge.

Neurosteroids and Ischemic Stroke: Progesterone a Promising Agent in Reducing the Brain Injury in Ischemic Stroke.

Science.gov (United States)

Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

2017-01-01

Progesterone (P4), a well-known neurosteroid, is produced by ovaries and placenta in females and by adrenal glands in both sexes. Progesterone is also synthesized by central nervous system (CNS) tissues to perform various vital neurological functions in the brain. Apart from performing crucial reproductive functions, it also plays a pivotal role in neurogenesis, regeneration, cognition, mood, inflammation, and myelination in the CNS. A substantial body of experimental evidence from animal models documents the neuroprotective role of P4 in various CNS injury models, including ischemic stroke. Extensive data have revealed that P4 elicits neuroprotection through multiple mechanisms and systems in an integrated manner to prevent neuronal and glial damage, thus reducing mortality and morbidity. Progesterone has been described as safe for use at the clinical level through different routes in several studies. Data regarding the neuroprotective role of P4 in ischemic stroke are of great interest due to their potential clinical implications. In this review, we succinctly discuss the biosynthesis of P4 and distribution of P4 receptors (PRs) in the brain. We summarize our work on the general mechanisms of P4 mediated via the modulation of different PR and neurotransmitters. Finally, we describe the neuroprotective mechanisms of P4 in ischemic stroke models and related clinical prospects.

Animal welfare and use of silkworm as a model animal.

Science.gov (United States)

Sekimizu, N; Paudel, A; Hamamoto, H

2012-08-01

Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare.

Modelling Farm Animal Welfare

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Chérie E. Part

2013-05-01

Full Text Available The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested.

Implication of Mauk Nursing Rehabilitation Model on Adjustment of Stroke Patients

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Zeinab Ebrahimpour mouziraji

2014-12-01

Full Text Available Objectives: Stroke is a neurological syndrome with sudden onset or gradual destruction of brain vessels, which may take 24 hours or more. Complications of stroke effect in the variation aspects of the individual. According to De Spulveda and Chang’s Studies, disability reduced the effective adjustment. This study aimed to overview the adjustment of stroke patients based on the main concepts of rehabilitation nursing Mauk model. Methods: In a quasi-experimental one group pre-posttest design study, data was collected in the neurology clinic of Imam Khomeini hospital and stroke patient rehabilitation centers in Tehran (Tabassom. Data collection included demographic and adjustment questionnaires of stroke patients. The intervention included seven sessions as Mauk model, each session with one hour training, for seven patients. Data analysis performed with SPSS software with paired t-test and was compared with previous results. Results: There were significant differences between the mean scores of patients with stroke adjustment questionnaire in the pre-test-post-test. But in the adjustment sub-scales, except for relationship with wife and Personal adjustment, in other areas, there is no statistically significant difference between the pre and posttest. Discussion: The results indicated that training has been affected on some aspects of adjustment of stroke patients in order to, as improving functions, complications and its limitations. Nurses can help then with implementing of plans such as patients education in this regard.

Queue-based modelling and detection of parameters involved in stroke outcome

DEFF Research Database (Denmark)

Vilic, Adnan; Petersen, John Asger; Wienecke, Troels

2017-01-01

We designed a queue-based model, and investigated which parameters are of importance when predicting stroke outcome. Medical record forms have been collected for 57 ischemic stroke patients, including medical history and vital sign measurement along with neurological scores for the first twenty...

The Role of Citicoline in Neuroprotection and Neurorepair in Ischemic Stroke

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Gustavo C. Román

2013-09-01

Full Text Available Advances in acute stroke therapy resulting from thrombolytic treatment, endovascular procedures, and stroke units have improved significantly stroke survival and prognosis; however, for the large majority of patients lacking access to advanced therapies stroke mortality and residual morbidity remain high and many patients become incapacitated by motor and cognitive deficits, with loss of independence in activities of daily living. Therefore, over the past several years, research has been directed to limit the brain lesions produced by acute ischemia (neuroprotection and to increase the recovery, plasticity and neuroregenerative processes that complement rehabilitation and enhance the possibility of recovery and return to normal functions (neurorepair. Citicoline has therapeutic effects at several stages of the ischemic cascade in acute ischemic stroke and has demonstrated efficiency in a multiplicity of animal models of acute stroke. Long-term treatment with citicoline is safe and effective, improving post-stroke cognitive decline and enhancing patients’ functional recovery. Prolonged citicoline administration at optimal doses has been demonstrated to be remarkably well tolerated and to enhance endogenous mechanisms of neurogenesis and neurorepair contributing to physical therapy and rehabilitation.

Dietary Polyphenols in the Prevention of Stroke

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A. Tressera-Rimbau

2017-01-01

Full Text Available Polyphenols have an important protective role against a number of diseases, such as atherosclerosis, brain dysfunction, stroke, cardiovascular diseases, and cancer. Cardiovascular diseases are the number one cause of death worldwide: more people die annually from cardiovascular diseases than from any other cause. The most important behavioural risk factors of heart disease and stroke are unhealthy diet, physical inactivity, tobacco use, and excess alcohol intake. The dietary consumption of polyphenols has shown to be inversely associated with morbidity and mortality by cardio- and cerebrovascular diseases. It is well-known that the protective effects of polyphenols in vivo depend on the grade how they are extracted from food and on their intestinal absorption, metabolism, and biological action with target tissues. The aim of this review was to summarise the relation between polyphenols of different plant sources and stroke in human intervention studies, animal models, and in vitro studies.

Dietary Polyphenols in the Prevention of Stroke

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Eder, M.

2017-01-01

Polyphenols have an important protective role against a number of diseases, such as atherosclerosis, brain dysfunction, stroke, cardiovascular diseases, and cancer. Cardiovascular diseases are the number one cause of death worldwide: more people die annually from cardiovascular diseases than from any other cause. The most important behavioural risk factors of heart disease and stroke are unhealthy diet, physical inactivity, tobacco use, and excess alcohol intake. The dietary consumption of polyphenols has shown to be inversely associated with morbidity and mortality by cardio- and cerebrovascular diseases. It is well-known that the protective effects of polyphenols in vivo depend on the grade how they are extracted from food and on their intestinal absorption, metabolism, and biological action with target tissues. The aim of this review was to summarise the relation between polyphenols of different plant sources and stroke in human intervention studies, animal models, and in vitro studies. PMID:29204249

OPLS statistical model versus linear regression to assess sonographic predictors of stroke prognosis.

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Vajargah, Kianoush Fathi; Sadeghi-Bazargani, Homayoun; Mehdizadeh-Esfanjani, Robab; Savadi-Oskouei, Daryoush; Farhoudi, Mehdi

2012-01-01

The objective of the present study was to assess the comparable applicability of orthogonal projections to latent structures (OPLS) statistical model vs traditional linear regression in order to investigate the role of trans cranial doppler (TCD) sonography in predicting ischemic stroke prognosis. The study was conducted on 116 ischemic stroke patients admitted to a specialty neurology ward. The Unified Neurological Stroke Scale was used once for clinical evaluation on the first week of admission and again six months later. All data was primarily analyzed using simple linear regression and later considered for multivariate analysis using PLS/OPLS models through the SIMCA P+12 statistical software package. The linear regression analysis results used for the identification of TCD predictors of stroke prognosis were confirmed through the OPLS modeling technique. Moreover, in comparison to linear regression, the OPLS model appeared to have higher sensitivity in detecting the predictors of ischemic stroke prognosis and detected several more predictors. Applying the OPLS model made it possible to use both single TCD measures/indicators and arbitrarily dichotomized measures of TCD single vessel involvement as well as the overall TCD result. In conclusion, the authors recommend PLS/OPLS methods as complementary rather than alternative to the available classical regression models such as linear regression.

Animal models of maternal nutrition and altered offspring bone structure – Bone development across the lifecourse

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SA Lanham

2011-11-01

Full Text Available It is widely accepted that the likelihood of offspring developing heart disease, stroke, or diabetes in later life, is influenced by the their in utero environment and maternal nutrition. There is increasing epidemiological evidence that osteoporosis in the offspring may also be influenced by the mother’s nutrition during pregnancy. This review provides evidence from a range of animal models that supports the epidemiological data; suggesting that lifelong bone development and growth in offspring is determined during gestation.

High-gradient operators in the psl(2 vertical stroke 2) Gross-Neveu model

International Nuclear Information System (INIS)

Cagnazzo, Alessandra; Schomerus, Volker; Tlapak, Vaclav

2014-10-01

It has been observed more than 25 years ago that sigma model perturbation theory suffers from strongly RG-relevant high-gradient operators. The phenomenon was first seen in 1-loop calculations for the O(N) vector model and it is known to persist at least to two loops. More recently, Ryu et al. suggested that a certain deformation of the psl(N vertical stroke N) WZNW-model at level k=1, or equivalently the psl(N vertical stroke N) Gross-Neveu model, could be free of RG-relevant high-gradient operators and they tested their suggestion to leading order in perturbation theory. In this note we establish the absence of strongly RG-relevant high-gradient operators in the psl(2 vertical stroke 2) Gross-Neveu model to all loops. In addition, we determine the spectrum for a large subsector of the model at infinite coupling and observe that all scaling weights become half-integer. Evidence for a conjectured relation with the CP 1 vertical stroke 2 sigma model is not found.

Splenectomy Does Not Improve Long-Term Outcome After Stroke.

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Zierath, Dannielle; Shen, Angela; Stults, Astiana; Olmstead, Theresa; Becker, Kyra J

2017-02-01

Immune responses to brain antigens after stroke contribute to poor outcome. We hypothesized that splenectomy would lessen the development of such responses and improve outcome. Male Lewis rats (275-350 g) underwent 2-hour middle cerebral artery occlusion immediately after splenectomy or sham splenectomy. Animals were survived to 4 weeks (672 hrs), and immune responses to myelin basic protein determined at euthanasia. Infarct volume was determined in a subset of animals euthanized at 72 hours. Behavioral outcomes were assessed to 672 hours. Splenectomy was associated with worse neurological scores early after stroke, but infarct size at 72 hours was similar in both groups. Behavioral outcomes and immune responses to myelin basic protein were also similar among splenectomized and sham-operated animals 672 hours after middle cerebral artery occlusion. Splenectomy did not alter the immune responses to brain antigens or improve outcome after stroke. Differences between this study and other studies of splenectomy and stroke are examined. © 2017 American Heart Association, Inc.

MR imaging of cerebral lesions accompanying stroke in stroke-prone spontaneously hypertensive rats

International Nuclear Information System (INIS)

Takahashi, Masaya; Fritz-Zieroth, B.; Yamaguchi, Motonori; Ogawa, Hiroshi; Tanaka, Tomoyo; Sasagawa, Sukenari; Chikugo, Taka-aki; Ohta, Yoshio; Okamoto, Kozo.

1992-01-01

Cerebral lesions accompanying stroke in male stroke-prone spontaneously hypertensive rats (SHRSP, n=10) were examined by both magnetic resonance imaging (MRI) and histological evaluation. T2-weighted MR images (T2-WI), taken 1-2 days after animals showed behavioral hyperactivity, indicated hyperintense regions in the occipital cortex, caudate putamen and/or thalamus. The areas of hyperintensity on T2-WI corresponded to neurodegenerative regions including edema, gliosis, and softening of the tissue. T1-weighted images (T1-WI) did not show any hyperintense regions. However T1-weighted images enhanced by the contrast media Gd-DTPA (Gd-T1-WI) showed hyperintense spots within some of the hyperintense areas on T2-WI, which exhibited neurodegenerative regions such as thrombus, angionecrosis and hemorrhage in addition to the edematous formation. The hyperintense areas on Gd-T1-WI were smaller than those on T2-WI. In some animals, hypointense spots on T2-, T1- and Gd-T1-WI were found within the hyperintense areas, which corresponded to clots. Extensive histological examination did not reveal any additional cerebral degeneration which had not been detected on the MR images. These findings indicate that MRI is useful for detecting and differentiating various types of cerebrovascular diseases in this model. (author)

MR imaging of cerebral lesions accompanying stroke in stroke-prone spontaneously hypertensive rats

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Takahashi, Masaya; Fritz-Zieroth, B.; Yamaguchi, Motonori (Nihon Schering K.K., Osaka (Japan)); Ogawa, Hiroshi; Tanaka, Tomoyo; Sasagawa, Sukenari; Chikugo, Taka-aki; Ohta, Yoshio; Okamoto, Kozo

1992-07-01

Cerebral lesions accompanying stroke in male stroke-prone spontaneously hypertensive rats (SHRSP, n=10) were examined by both magnetic resonance imaging (MRI) and histological evaluation. T2-weighted MR images (T2-WI), taken 1-2 days after animals showed behavioral hyperactivity, indicated hyperintense regions in the occipital cortex, caudate putamen and/or thalamus. The areas of hyperintensity on T2-WI corresponded to neurodegenerative regions including edema, gliosis, and softening of the tissue. T1-weighted images (T1-WI) did not show any hyperintense regions. However T1-weighted images enhanced by the contrast media Gd-DTPA (Gd-T1-WI) showed hyperintense spots within some of the hyperintense areas on T2-WI, which exhibited neurodegenerative regions such as thrombus, angionecrosis and hemorrhage in addition to the edematous formation. The hyperintense areas on Gd-T1-WI were smaller than those on T2-WI. In some animals, hypointense spots on T2-, T1- and Gd-T1-WI were found within the hyperintense areas, which corresponded to clots. Extensive histological examination did not reveal any additional cerebral degeneration which had not been detected on the MR images. These findings indicate that MRI is useful for detecting and differentiating various types of cerebrovascular diseases in this model. (author).

Risk Factors and Stroke Characteristic in Patients with Postoperative Strokes.

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Dong, Yi; Cao, Wenjie; Cheng, Xin; Fang, Kun; Zhang, Xiaolong; Gu, Yuxiang; Leng, Bing; Dong, Qiang

2017-07-01

Intravenous thrombolysis and intra-arterial thrombectomy are now the standard therapies for patients with acute ischemic stroke. In-house strokes have often been overlooked even at stroke centers and there is no consensus on how they should be managed. Perioperative stroke happens rather frequently but treatment protocol is lacking, In China, the issue of in-house strokes has not been explored. The aim of this study is to explore the current management of in-house stroke and identify the common risk factors associated with perioperative strokes. Altogether, 51,841 patients were admitted to a tertiary hospital in Shanghai and the records of those who had a neurological consult for stroke were reviewed. Their demographics, clinical characteristics, in-hospital complications and operations, and management plans were prospectively studied. Routine laboratory test results and risk factors of these patients were analyzed by multiple logistic regression model. From January 1, 2015, to December 31, 2015, over 1800 patients had neurological consultations. Among these patients, 37 had an in-house stroke and 20 had more severe stroke during the postoperative period. Compared to in-house stroke patients without a procedure or operation, leukocytosis and elevated fasting glucose levels were more common in perioperative strokes. In multiple logistic regression model, perioperative strokes were more likely related to large vessel occlusion. Patients with perioperative strokes had different risk factors and severity from other in-house strokes. For these patients, obtaining a neurological consultation prior to surgery may be appropriate in order to evaluate the risk of perioperative stroke. Copyright © 2017. Published by Elsevier Inc.

Animal models of tinnitus.

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Brozoski, Thomas J; Bauer, Carol A

2016-08-01

Presented is a thematic review of animal tinnitus models from a functional perspective. Chronic tinnitus is a persistent subjective sound sensation, emergent typically after hearing loss. Although the sensation is experientially simple, it appears to have central a nervous system substrate of unexpected complexity that includes areas outside of those classically defined as auditory. Over the past 27 years animal models have significantly contributed to understanding tinnitus' complex neurophysiology. In that time, a diversity of models have been developed, each with its own strengths and limitations. None has clearly become a standard. Animal models trace their origin to the 1988 experiments of Jastreboff and colleagues. All subsequent models derive some of their features from those experiments. Common features include behavior-dependent psychophysical determination, acoustic conditions that contrast objective sound and silence, and inclusion of at least one normal-hearing control group. In the present review, animal models have been categorized as either interrogative or reflexive. Interrogative models use emitted behavior under voluntary control to indicate hearing. An example would be pressing a lever to obtain food in the presence of a particular sound. In this type of model animals are interrogated about their auditory sensations, analogous to asking a patient, "What do you hear?" These models require at least some training and motivation management, and reflect the perception of tinnitus. Reflexive models, in contrast, employ acoustic modulation of an auditory reflex, such as the acoustic startle response. An unexpected loud sound will elicit a reflexive motor response from many species, including humans. Although involuntary, acoustic startle can be modified by a lower-level preceding event, including a silent sound gap. Sound-gap modulation of acoustic startle appears to discriminate tinnitus in animals as well as humans, and requires no training or

The SU(2 vertical stroke 3) spin chain sigma model

International Nuclear Information System (INIS)

Hernandez, R.; Lopez, E.

2005-01-01

The one-loop planar dilatation operator of N = 4 supersymmetric Yang-Mills is isomorphic to the hamiltonian of an integrable PSU(2,2 vertical stroke 4) spin chain. We construct the non-linear sigma model describing the continuum limit of the SU(2 vertical stroke 3) subsector of the N = 4 chain. We explicitly identify the spin chain sigma model with the one for a superstring moving in AdS 5 x S 5 with large angular momentum along the five-sphere. (Abstract Copyright [2005], Wiley Periodicals, Inc.)

Urinary Retention Associated with Stroke.

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Umemura, Takeru; Ohta, Hirotsugu; Yokota, Akira; Yarimizu, Shiroh; Nishizawa, Shigeru

Patients often exhibit urinary retention following a stroke. Various neuropathological and animal studies have implicated the medulla oblongata, pons, limbic system, frontal lobe as areas responsible for micturition control, although the exact area responsible for urinary retention after stroke is not clear. The purpose of this study was to identify the stroke area responsible for urinary retention by localizing the areas where strokes occur. We assessed 110 patients with cerebral infarction and 27 patients with cerebral hemorrhage (78 men, 59 women; mean age, 73.0 years) who had been admitted to our hospital between October, 2012 and September, 2013. We used computed tomography (CT) and magnetic resonance imaging (MRI) to investigate the stroke location, and evaluated whether post-stroke urinary retention occurred. Twelve (8.8%) of the 137 patients (7 men, 5 women; mean age, 78.8 years) exhibited urinary retention after a stroke. Stroke occurred in the right/left dominant hemisphere in 7 patients; nondominant hemisphere in 1; cerebellum in 3; and brainstem in 1. Strokes in the dominant hemisphere were associated with urinary retention (P = 0.0314), particularly in the area of the insula (P < 0.01). We concluded that stroke affecting the insula of the dominant hemisphere tends to cause urinary retention.

The site of embolization related to infarct size, oedema and clinical outcome in a rat stroke model - further translational stroke research

DEFF Research Database (Denmark)

Overgaard, Karsten; Rasmussen, Rune S; Johansen, Flemming F

2010-01-01

Reliable models are essential for translational stroke research to study the pathophysiology of ischaemic stroke in an effort to find therapies that may ultimately reduce oedema, infarction and mortality in the clinic. The purpose of this study was to investigate the relation between the site...

Hydrodynamic interactions in metachronal paddling: effects of varying stroke kinematics

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Samaee, Milad; Kasoju, Vishwa; Lai, Hong Kuan; Santhanakrishnan, Arvind

2017-11-01

Crustaceans such as shrimp and krill use a drag-based technique for propulsion, in which multiple pairs of limbs are paddled rhythmically from the tail to the head. Each limb is phase-shifted in time relative to its neighbor. Most studies of this type of metachronal swimming have focused on the jet formed in the animal's wake. However, synergistic hydrodynamic interactions between adjacent limbs in metachrony have received minimal attention. We used a dynamically scaled robotic model to experimentally investigate how variations in stroke kinematics impact inter-paddle hydrodynamic interactions and thrust generation. Physical models of limbs were fitted to the robot and paddled with two different motion profiles (MPs)-1) MP1: metachronal power stroke (PS) and metachronal recovery stroke (RS); and 2) MP2: metachronal PS and synchronous RS. Stroke frequency and amplitude were maintained constant across both MPs. Our results show that MP2 produced faster jets in the thrust-generating direction as compared to MP1. The necessity for a pause in MP2 after completion of PS by the paddles leading the motion, prior to executing the synchronous RS, aided in further downstream flow propagation. The effect of using asymmetric stroke kinematics on thrust generated will be discussed.

Animal models of sarcoidosis.

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Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M

2017-03-01

Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

A visible Chinese human-combined Monte Carlo simulation study on low-level light therapy of stroke

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Wang, Pengbo; Pan, Boan; Zhong, Fulin; Li, Ting

2017-02-01

Stroke is a devastating disease, which is the third leading cause of death and disability worldwide. Although the incidence of stroke increases progressively with age, morbidity among young and middle-aged adults is increasing annually. Medications nevertheless remain the bulwarks of stroke. The treatment is ineffective, speculative and has a long treatment cycle. The function of acupuncture and moxibustion, which are potential therapeutic tools for stroke, is still controversial. Recently, Low-level light therapy (LLLT) has been demonstrated potent in vivo efficacy for treatment of ischemic conditions of acute myocardial infraction and stroke in multiple validated animal models. Optimum LLLT treatment has a dominant influence on therapy of stroke. While more than a thousand clinical trials have been halted, only a few trials on animals have been reported. We addressed this issue by simulating near-infrared light propagation with accurate visible Chinese human head by Monte Carlo modeling. The visible human head embody region of atherosclerotic plaques in head. Through comparing the light propagation of different light illumination, we can get a precise, optimized and straightforward treatment. Here, we developed a LLLT helmet for treating stroke depend on near-infrared light. There are more than 30 LED arrays in in multi-layered 3D printed helmet. Each LED array has independent water-cooling module and can be adjusted to touch the head of different subjects based on Electro pneumatic module. Moreover, the software provides the setup of illumination parameters and 3D distribution of light fluence rate distribution in human brain.

Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke.

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Khodaparast, Navid; Hays, Seth A; Sloan, Andrew M; Fayyaz, Tabbassum; Hulsey, Daniel R; Rennaker, Robert L; Kilgard, Michael P

2014-09-01

Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into 3 groups: vagus nerve stimulation during rehabilitation (rehab), vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), prelesion training, postlesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed 1 week of recovery before postlesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All 17 trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to prelesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to prelesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared with rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. © The Author(s) 2014.

Animal Models of Diabetic Macrovascular Complications: Key Players in the Development of New Therapeutic Approaches

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Suvi E. Heinonen

2015-01-01

Full Text Available Diabetes mellitus is a lifelong, incapacitating metabolic disease associated with chronic macrovascular complications (coronary heart disease, stroke, and peripheral vascular disease and microvascular disorders leading to damage of the kidneys (nephropathy and eyes (retinopathy. Based on the current trends, the rising prevalence of diabetes worldwide will lead to increased cardiovascular morbidity and mortality. Therefore, novel means to prevent and treat these complications are needed. Under the auspices of the IMI (Innovative Medicines Initiative, the SUMMIT (SUrrogate markers for Micro- and Macrovascular hard end points for Innovative diabetes Tools consortium is working on the development of novel animal models that better replicate vascular complications of diabetes and on the characterization of the available models. In the past years, with the high level of genomic information available and more advanced molecular tools, a very large number of models has been created. Selecting the right model for a specific study is not a trivial task and will have an impact on the study results and their interpretation. This review gathers information on the available experimental animal models of diabetic macrovascular complications and evaluates their pros and cons for research purposes as well as for drug development.

[Cellular composition of lymphoid nodules in the trachea wall in rats with different resistance to emotional stress in a model of hemorrhagic stroke].

Science.gov (United States)

Klyueva, L A

2017-01-01

To reveal regularities of changes in cellular composition of lymphoid nodules in the tracheal wall in male Wistar rats resistant and not resistant to emotional stress in a model of hemorrhagic stroke. Lymphoid formations of the tracheal wall (an area near the bifurcation of the organ) were investigated in 98 male Wistar rats using histological methods. Significant changes in the cellular composition of lymphoid nodules were found. The pattern of changes depends on the stress resistance of rats and the period of the experiment. The active cell destruction in lymphoid nodules was noted both in stress resistant and stress susceptible animals. The changes in the structure of lymphoid nodules found in the experimental hemorrhagic stroke suggest a decrease in the local immune resistance, which is most pronounced in rats not resistant to stress, that may contribute to the development of severe inflammatory complications of stroke such as pneumonia.

A review of novel optical imaging strategies of the stroke pathology and stem cell therapy in stroke

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Markus eAswendt

2014-08-01

Full Text Available Transplanted stem cells can induce and enhance functional recovery in experimental stroke. Invasive analysis has been extensively used to provide detailed cellular and molecular characterization of the stroke pathology and engrafted stem cells. But post mortem analysis is not appropriate to reveal the time scale of the dynamic interplay between the cell graft, the ischemic lesion and the endogenous repair mechanisms. This review describes non-invasive imaging techniques which have been developed to provide complementary in vivo information. Recent advances were made in analyzing simultaneously different aspects of the cell graft (e.g. number of cells, viability state and cell fate, the ischemic lesion (e.g. blood brain barrier consistency, hypoxic and necrotic areas and the neuronal and vascular network. We focus on optical methods, which permit simple animal preparation, repetitive experimental conditions, relatively medium-cost instrumentation and are performed under mild anesthesia, thus nearly under physiological conditions. A selection of recent examples of optical intrinsic imaging, fluorescence imaging (FLI and bioluminescence imaging (BLI to characterize the stroke pathology and engrafted stem cells are discussed. Special attention is paid to novel optimal reporter genes/probes for genetic labeling and tracking of stem cells and appropriate transgenic animal models. Requirements, advantages and limitations of these imaging platforms are critically discussed and placed into the context of other non-invasive techniques, e.g. magnetic resonance imaging (MRI and positron emission tomography (PET, which can be joined with optical imaging in multimodal approaches.

Thrombolytic and anticoagulation treatment in a rat embolic stroke model

DEFF Research Database (Denmark)

Rasmussen, Rune Skovgaard; Overgaard, K; Meden, P

2003-01-01

OBJECTIVES: The effects of pentasaccharide (PENTA), given alone or combined with thrombolysis using recombinant tissue plasminogen activator (rt-PA), on infarct size and clinical outcome were evaluated in a rat embolic stroke model. MATERIALS AND METHODS: Ninety-two rats were embolized unilateral...... alone or combined with rt-PA did not significantly increase mortality or tendency for hemorrhage.......OBJECTIVES: The effects of pentasaccharide (PENTA), given alone or combined with thrombolysis using recombinant tissue plasminogen activator (rt-PA), on infarct size and clinical outcome were evaluated in a rat embolic stroke model. MATERIALS AND METHODS: Ninety-two rats were embolized unilaterally...

On the SU(2 vertical stroke 1) WZNW model and its statistical mechanics applications

Energy Technology Data Exchange (ETDEWEB)

Saleur, H [CEA Centre d' Etudes de Saclay, 91 - Gif-sur-Yvette (France). Service de Physique Theorique; [University of Southern California, Los Angeles, CA (United States). Dept. of Physics; Schomerus, V [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

2006-11-15

Motivated by a careful analysis of the Laplacian on the supergroup SU(2 vertical stroke 1) we formulate a proposal for the state space of the SU(2 vertical stroke 1) WZNW model. We then use properties of sl(2 vertical stroke 1) characters to compute the partition function of the theory. In the special case of level k=1 the latter is found to agree with the properly regularized partition function for the continuum limit of the integrable sl(2 vertical stroke 1)3- anti 3 super-spin chain. Some general conclusions applicable to other WZNW models (in particular the case k=-1/2) are also drawn. (orig.)

Neurochemical changes underpinning the development of adjunct therapies in recovery after stroke: A role for GABA?

Science.gov (United States)

Johnstone, Ainslie; Levenstein, Jacob M; Hinson, Emily L; Stagg, Charlotte J

2017-01-01

Stroke is a leading cause of long-term disability, with around three-quarters of stroke survivors experiencing motor problems. Intensive physiotherapy is currently the most effective treatment for post-stroke motor deficits, but much recent research has been targeted at increasing the effects of the intervention by pairing it with a wide variety of adjunct therapies, all of which aim to increase cortical plasticity, and thereby hope to maximize functional outcome. Here, we review the literature describing neurochemical changes underlying plasticity induction following stroke. We discuss methods of assessing neurochemicals in humans, and how these measurements change post-stroke. Motor learning in healthy individuals has been suggested as a model for stroke plasticity, and we discuss the support for this model, and what evidence it provides for neurochemical changes. One converging hypothesis from animal, healthy and stroke studies is the importance of the regulation of the inhibitory neurotransmitter GABA for the induction of cortical plasticity. We discuss the evidence supporting this hypothesis, before finally summarizing the literature surrounding the use of adjunct therapies such as non-invasive brain stimulation and SSRIs in post-stroke motor recovery, both of which have been show to influence the GABAergic system.

Animal Models in Burn Research

Science.gov (United States)

Abdullahi, A.; Amini-Nik, S.; Jeschke, M.G

2014-01-01

Burn injury is a severe form of trauma affecting more than two million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury; to elucidate the pathophysiology and explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review paper aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research. PMID:24714880

A comparison of different models of stroke on behaviour and brain morphology.

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Gonzalez, C L R; Kolb, B

2003-10-01

We compared the effects of three models of permanent ischemia, as well as cortical aspiration, on behaviour and brain morphology. Rats received a stroke either by devascularization or by two different procedures of medial cerebral artery occlusion (MCAO; small vs. large). Animals were trained in a reaching task, forepaw asymmetry, forepaw inhibition, sunflower seed task and tongue extension. Behaviour was assessed 1 week after the lesion and at 2-week intervals for a total of 9 weeks. One week after the surgery all animals were severely impaired on all tasks and although they improved over time they only reached preoperative base lines on tongue extension. Animals with small MCAOs performed better in reaching and sunflower tasks; no other behavioural differences were detected among the groups. Pyramidal cells in forelimb and cingulate areas as well as spiny neurons of the striatum were examined for dendritic branching and spine density using a Golgi-Cox procedure. Each lesion type had a different impact on cell morphology. Overall, different changes (atrophy or hypertrophy) were observed with each kind of lesion and these changes were specific for the region (forelimb, cingulate, striatum) and the condition (intact vs. damaged hemisphere). These results suggest that: (i) different lesions to the motor cortex produce subtle differences in behaviour, and (ii) the method used to induce the lesion produces striking differences in cortical and subcortical plasticity.

Herbal Medicine in Ischemic Stroke: Challenges and Prospective.

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Gaire, Bhakta Prasad

2018-04-01

Herbal medicines, mainly of plant source, are invaluable source for the discovery of new therapeutic agents for all sorts of human ailments. The complex pathogenesis of stroke and multifactorial effect of herbal medicine and their active constituents may suggest the promising future of natural medicine for stroke treatment. Anti-oxidant, anti-inflammatory, anti-apoptotic, neuroprotective and vascular protective effect of herbal medicines are believed to be efficacious in stroke treatment. Herbs typically have fewer reported side effects than allopathic medicine, and may be safer to use over longer period of time. Herbal medicines are believed to be more effective for the longstanding health complaints, such as stroke. Several medicinal plants and their active constituents show the promising results in laboratory research. However failure in transformation of laboratory animal research to the clinical trials has created huge challenge for the use of herbal medicine in stroke. Until and unless scientifically comprehensive evidence of the efficacy and safety of herbal medicine in ischemic stroke patients is available, efforts should be made to continue implementing treatment strategies of proven effectiveness. More consideration should be paid to natural compounds that can have extensive therapeutic time windows, perfect pharmacological targets with few side effects. Herbal medicine has excellent prospective for the treatment of ischemic stroke, but a lot of effort should be invested to transform the success of animal research to human use.

Family caregiver adjustment and stroke survivor impairment: A path analytic model.

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Pendergrass, Anna; Hautzinger, Martin; Elliott, Timothy R; Schilling, Oliver; Becker, Clemens; Pfeiffer, Klaus

2017-05-01

Depressive symptoms are a common problem among family caregivers of stroke survivors. The purpose of this study was to examine the association between care recipient's impairment and caregiver depression, and determine the possible mediating effects of caregiver negative problem-orientation, mastery, and leisure time satisfaction. The evaluated model was derived from Pearlin's stress process model of caregiver adjustment. We analyzed baseline data from 122 strained family members who were assisting stroke survivors in Germany for a minimum of 6 months and who consented to participate in a randomized clinical trial. Depressive symptoms were measured with the Center for Epidemiological Studies Depression Scale. The cross-sectional data were analyzed using path analysis. The results show an adequate fit of the model to the data, χ2(1, N = 122) = 0.17, p = .68; comparative fit index = 1.00; root mean square error of approximation: p caregiver depressive symptoms. Results indicate that caregivers at risk for depression reported a negative problem orientation, low caregiving mastery, and low leisure time satisfaction. The situation is particularly affected by the frequency of stroke survivor problematic behavior, and by the degree of their impairments in activities of daily living. The findings provide empirical support for the Pearlin's stress model and emphasize how important it is to target these mediators in health promotion interventions for family caregivers of stroke survivors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The development and implementation of stroke risk prediction model in National Health Insurance Service's personal health record.

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Lee, Jae-Woo; Lim, Hyun-Sun; Kim, Dong-Wook; Shin, Soon-Ae; Kim, Jinkwon; Yoo, Bora; Cho, Kyung-Hee

2018-01-01

The purpose of this study was to build a 10-year stroke prediction model and categorize a probability of stroke using the Korean national health examination data. Then it intended to develop the algorithm to provide a personalized warning on the basis of each user's level of stroke risk and a lifestyle correction message about the stroke risk factors. Subject to national health examinees in 2002-2003, the stroke prediction model identified when stroke was first diagnosed by following-up the cohort until 2013 and estimated a 10-year probability of stroke. It sorted the user's individual probability of stroke into five categories - normal, slightly high, high, risky, very risky, according to the five ranges of average probability of stroke in comparison to total population - less than 50 percentile, 50-70, 70-90, 90-99.9, more than 99.9 percentile, and constructed the personalized warning and lifestyle correction messages by each category. Risk factors in stroke risk model include the age, BMI, cholesterol, hypertension, diabetes, smoking status and intensity, physical activity, alcohol drinking, past history (hypertension, coronary heart disease) and family history (stroke, coronary heart disease). The AUC values of stroke risk prediction model from the external validation data set were 0.83 in men and 0.82 in women, which showed a high predictive power. The probability of stroke within 10 years for men in normal group (less than 50 percentile) was less than 3.92% and those in very risky group (top 0.01 percentile) was 66.2% and over. The women's probability of stroke within 10 years was less than 3.77% in normal group (less than 50 percentile) and 55.24% and over in very risky group. This study developed the stroke risk prediction model and the personalized warning and the lifestyle correction message based on the national health examination data and uploaded them to the personal health record service called My Health Bank in the health information website - Health

Modeling of Lightning Strokes Using Two-Peaked Channel-Base Currents

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V. Javor

2012-01-01

Full Text Available Lightning electromagnetic field is obtained by using “engineering” models of lightning return strokes and new channel-base current functions and the results are presented in this paper. Experimentally measured channel-base currents are approximated not only with functions having two-peaked waveshapes but also with the one-peaked function so as usually used in the literature. These functions are simple to be applied in any “engineering” or electromagnetic model as well. For the three “engineering” models: transmission line model (without the peak current decay, transmission line model with linear decay, and transmission line model with exponential decay with height, the comparison of electric and magnetic field components at different distances from the lightning channel-base is presented in the case of a perfectly conducting ground. Different heights of lightning channels are also considered. These results enable analysis of advantages/shortages of the used return stroke models according to the electromagnetic field features to be achieved, as obtained by measurements.

Extension of Tissue Plasminogen Activator Treatment Window by Granulocyte-Colony Stimulating Factor in a Thromboembolic Rat Model of Stroke

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Ike C. dela Peña

2018-05-01

Full Text Available When given beyond 4.5 h of stroke onset, tissue plasminogen activator (tPA induces deleterious side effects in the ischemic brain, notably, hemorrhagic transformation (HT. We examined the efficacy of granulocyte-colony stimulating factor (G-CSF in reducing delayed tPA-induced HT, cerebral infarction, and neurological deficits in a thromboembolic (TE stroke model, and whether the effects of G-CSF were sustained for longer periods of recovery. After stroke induction, rats were given intravenous saline (control, tPA (10 mg/kg, or G-CSF (300 μg/kg + tPA 6 h after stroke. We found that G-CSF reduced delayed tPA-associated HT by 47%, decreased infarct volumes by 33%, and improved motor and neurological deficits by 15% and 25%, respectively. It also prevented delayed tPA treatment-induced mortality by 46%. Immunohistochemistry showed 1.5- and 1.8-fold enrichment of the endothelial progenitor cell (EPC markers CD34+ and VEGFR2 in the ischemic cortex and striatum, respectively, and 1.7- and 2.8-fold increases in the expression of the vasculogenesis marker von Willebrand factor (vWF in the ischemic cortex and striatum, respectively, in G-CSF-treated rats compared with tPA-treated animals. Flow cytometry revealed increased mobilization of CD34+ cells in the peripheral blood of rats given G-CSF. These results corroborate the efficacy of G-CSF in enhancing the therapeutic time window of tPA for stroke treatment via EPC mobilization and enhancement of vasculogenesis.

Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

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Mohammad Reza Nikravesh

2011-11-01

Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

Minocycline treatment in acute stroke: an open-label, evaluator-blinded study.

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Lampl, Y; Boaz, M; Gilad, R; Lorberboym, M; Dabby, R; Rapoport, A; Anca-Hershkowitz, M; Sadeh, M

2007-10-02

Ischemic animal model studies have shown a neuroprotective effect of minocycline. To analyze the effect of minocycline treatment in human acute ischemic stroke. We performed an open-label, evaluator-blinded study. Minocycline at a dosage of 200 mg was administered orally for 5 days. The therapeutic window of time was 6 to 24 hours after onset of stroke. Data from NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) were evaluated. The primary objective was to compare changes from baseline to day 90 in NIHSS in the minocycline group vs placebo. One hundred fifty-two patients were included in the study. Seventy-four patients received minocycline treatment, and 77 received placebo. NIHSS and mRS were significantly lower and BI scores were significantly higher in minocycline-treated patients. This pattern was already apparent on day 7 and day 30 of follow-up. Deaths, myocardial infarctions, recurrent strokes, and hemorrhagic transformations during follow-up did not differ by treatment group. Patients with acute stroke had significantly better outcome with minocycline treatment compared with placebo. The findings suggest a potential benefit of minocycline in acute ischemic stroke.

Early post-stroke cognition in stroke rehabilitation patients predicts functional outcome at 13 months.

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Wagle, Jørgen; Farner, Lasse; Flekkøy, Kjell; Bruun Wyller, Torgeir; Sandvik, Leiv; Fure, Brynjar; Stensrød, Brynhild; Engedal, Knut

2011-01-01

To identify prognostic factors associated with functional outcome at 13 months in a sample of stroke rehabilitation patients. Specifically, we hypothesized that cognitive functioning early after stroke would predict long-term functional outcome independently of other factors. 163 stroke rehabilitation patients underwent a structured neuropsychological examination 2-3 weeks after hospital admittance, and their functional status was subsequently evaluated 13 months later with the modified Rankin Scale (mRS) as outcome measure. Three predictive models were built using linear regression analyses: a biological model (sociodemographics, apolipoprotein E genotype, prestroke vascular factors, lesion characteristics and neurological stroke-related impairment); a functional model (pre- and early post-stroke cognitive functioning, personal and instrumental activities of daily living, ADL, and depressive symptoms), and a combined model (including significant variables, with p value Stroke Scale; β = 0.402, p stroke cognitive functioning (Repeatable Battery of Neuropsychological Status, RBANS; β = -0.248, p = 0.001) and prestroke personal ADL (Barthel Index; β = -0.217, p = 0.002). Further linear regression analyses of which RBANS indexes and subtests best predicted long-term functional outcome showed that Coding (β = -0.484, p stroke cognitive functioning as measured by the RBANS is a significant and independent predictor of long-term functional post-stroke outcome. Copyright © 2011 S. Karger AG, Basel.

Stroke: working toward a prioritized world agenda.

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Hachinski, Vladimir; Donnan, Geoffrey A; Gorelick, Philip B; Hacke, Werner; Cramer, Steven C; Kaste, Markku; Fisher, Marc; Brainin, Michael; Buchan, Alastair M; Lo, Eng H; Skolnick, Brett E; Furie, Karen L; Hankey, Graeme J; Kivipelto, Miia; Morris, John; Rothwell, Peter M; Sacco, Ralph L; Smith, Sidney C; Wang, Yulun; Bryer, Alan; Ford, Gary A; Iadecola, Costantino; Martins, Sheila C O; Saver, Jeff; Skvortsova, Veronika; Bayley, Mark; Bednar, Martin M; Duncan, Pamela; Enney, Lori; Finklestein, Seth; Jones, Theresa A; Kalra, Lalit; Kleim, Jeff; Nitkin, Ralph; Teasell, Robert; Weiller, Cornelius; Desai, Bhupat; Goldberg, Mark P; Heiss, Wolf-Dieter; Saarelma, Osmo; Schwamm, Lee H; Shinohara, Yukito; Trivedi, Bhargava; Wahlgren, Nils; Wong, Lawrence K; Hakim, Antoine; Norrving, Bo; Prudhomme, Stephen; Bornstein, Natan M; Davis, Stephen M; Goldstein, Larry B; Leys, Didier; Tuomilehto, Jaakko

2010-01-01

The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (e.g., social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and

Stroke: Working toward a Prioritized World Agenda

Science.gov (United States)

Hachinski, Vladimir; Donnan, Geoffrey A.; Gorelick, Philip B.; Hacke, Werner; Cramer, Steven C.; Kaste, Markku; Fisher, Marc; Brainin, Michael; Buchan, Alastair M.; Lo, Eng H.; Skolnick, Brett E.; Furie, Karen L.; Hankey, Graeme J.; Kivipelto, Miia; Morris, John; Rothwell, Peter M.; Sacco, Ralph L.; Smith, Jr., Sidney C.; Wang, Yulun; Bryer, Alan; Ford, Gary A.; Iadecola, Costantino; Martins, Sheila C.O.; Saver, Jeff; Skvortsova, Veronika; Bayley, Mark; Bednar, Martin M.; Duncan, Pamela; Enney, Lori; Finklestein, Seth; Jones, Theresa A.; Kalra, Lalit; Kleim, Jeff; Nitkin, Ralph; Teasell, Robert; Weiller, Cornelius; Desai, Bhupat; Goldberg, Mark P.; Heiss, Wolf-Dieter; Saarelma, Osmo; Schwamm, Lee H.; Shinohara, Yukito; Trivedi, Bhargava; Wahlgren, Nils; Wong, Lawrence K.; Hakim, Antoine; Norrving, Bo; Prudhomme, Stephen; Bornstein, Natan M.; Davis, Stephen M.; Goldstein, Larry B.; Leys, Didier; Tuomilehto, Jaakko

2010-01-01

Background and Purpose The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent ‘silo’ mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (e.g., social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build

Stroke: working toward a prioritized world agenda.

Science.gov (United States)

Hachinski, Vladimir; Donnan, Geoffrey A; Gorelick, Philip B; Hacke, Werner; Cramer, Steven C; Kaste, Markku; Fisher, Marc; Brainin, Michael; Buchan, Alastair M; Lo, Eng H; Skolnick, Brett E; Furie, Karen L; Hankey, Graeme J; Kivipelto, Miia; Morris, John; Rothwell, Peter M; Sacco, Ralph L; Smith, Sidney C; Wang, Yulun; Bryer, Alan; Ford, Gary A; Iadecola, Costantino; Martins, Sheila C O; Saver, Jeff; Skvortsova, Veronika; Bayley, Mark; Bednar, Martin M; Duncan, Pamela; Enney, Lori; Finklestein, Seth; Jones, Theresa A; Kalra, Lalit; Kleim, Jeff; Nitkin, Ralph; Teasell, Robert; Weiller, Cornelius; Desai, Bhupat; Goldberg, Mark P; Heiss, Wolf-Dieter; Saarelma, Osmo; Schwamm, Lee H; Shinohara, Yukito; Trivedi, Bhargava; Wahlgren, Nils; Wong, Lawrence K; Hakim, Antoine; Norrving, Bo; Prudhomme, Stephen; Bornstein, Natan M; Davis, Stephen M; Goldstein, Larry B; Leys, Didier; Tuomilehto, Jaakko

2010-08-01

The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Preliminary work was performed by seven working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and

Circulating and brain BDNF levels in stroke rats. Relevance to clinical studies.

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Yannick Béjot

Full Text Available BACKGROUND: Whereas brain-derived neurotrophic factor (BDNF levels are measured in the brain in animal models of stroke, neurotrophin levels in stroke patients are measured in plasma or serum samples. The present study was designed to investigate the meaning of circulating BDNF levels in stroke patients. METHODS AND RESULTS: Unilateral ischemic stroke was induced in rats by the injection of various numbers of microspheres into the carotid circulation in order to mimic the different degrees of stroke severity observed in stroke patients. Blood was serially collected from the jugular vein before and after (4 h, 24 h and 8 d embolization and the whole brains were collected at 4, 24 h and 8 d post-embolization. Rats were then selected from their degree of embolization, so that the distribution of stroke severity in the rats at the different time points was large but similar. Using ELISA tests, BDNF levels were measured in plasma, serum and brain of selected rats. Whereas plasma and serum BDNF levels were not changed by stroke, stroke induced an increase in brain BDNF levels at 4 h and 24 h post-embolization, which was not correlated with stroke severity. Individual plasma BDNF levels did not correlate with brain levels at any time point after stroke but a positive correlation (r = 0.67 was observed between individual plasma BDNF levels and stroke severity at 4 h post-embolization. CONCLUSION: Circulating BDNF levels do not mirror brain BDNF levels after stroke, and severe stroke is associated with high plasma BDNF in the very acute stage.

Overview of Animal Models of Obesity

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Lutz, Thomas A.; Woods, Stephen C.

2012-01-01

This is a review of animal models of obesity currently used in research. We have focused upon more commonly utilized models since there are far too many newly created models to consider, especially those caused by selective molecular genetic approaches modifying one or more genes in specific populations of cells. Further, we will not discuss the generation and use of inducible transgenic animals (induced knock-out or knock-in) even though they often bear significant advantages compared to traditional transgenic animals; influences of the genetic modification during the development of the animals can be minimized. The number of these animal models is simply too large to be covered in this chapter. PMID:22948848

Dynamics of myelin content decrease in the rat stroke model

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Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

2017-08-01

The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

Erythropoietin in stroke therapy: friend or foe.

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Souvenir, Rhonda; Doycheva, Desislava; Zhang, John H; Tang, Jiping

2015-01-01

Recombinant human erythropoietin (rhEPO), over the past decade, was hailed as an auspicious therapeutic strategy for various types of brain injuries. The promising results from experiments conducted in animal models of stroke led to a hurried clinical trial that was swiftly aborted in Phase II. The multiple neuroprotective modalities of rhEPO failed to translate smoothly to human adult ischemic brain injury and provided limited aid to neonates. In light of the antithetical results, several questions were raised as to why and how this clinical trial failed. There was bolstering evidence from the preliminary studies that pointed to a bright future. Therefore, the objective of this review is to address these questions by discussing the signaling pathways of rhEPO that are reported to mediate the neuroprotective effect in various animal models of brain injury. Major biomedical bibliographical databases (MEDLINE, ISI, PubMed, and Cochrane Library) were searched with the use of keywords such as erythropoietin, stroke, neonatal hypoxia ischemia, intracerebral hemorrhage, etc. This article will discuss the confounding factors that influence the efficacy of rhEPO treatment hence challenging its clinical translatability. Lastly, rhEPO may still be a promising therapeutic candidate for neonates in spite of its shortcoming in clinical trial if caution is taken with the dose and duration of its administration.

Combining BMI stimulation and mathematical modeling for acute stroke recovery and neural repair

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Sara L Gonzalez Andino

2011-07-01

Full Text Available Rehabilitation is a neural plasticity-exploiting approach that forces undamaged neural circuits to undertake the functionality of other circuits damaged by stroke. It aims to partial restoration of the neural functions by circuit remodeling rather than by the regeneration of damaged circuits. The core hypothesis of the present paper is that - in stroke - Brain Machine Interfaces can be designed to target neural repair instead of rehabilitation. To support this hypothesis we first review existing evidence on the role of endogenous or externally applied electric fields on all processes involved in CNS repair. We then describe our own results to illustrate the neuroprotective and neuroregenerative effects of BMI- electrical stimulation on sensory deprivation-related degenerative processes of the CNS. Finally, we discuss three of the crucial issues involved in the design of neural repair-oriented BMIs: when to stimulate, where to stimulate and - the particularly important but unsolved issue of - how to stimulate. We argue that optimal parameters for the electrical stimulation can be determined from studying and modeling the dynamics of the electric fields that naturally emerge at the central and peripheral nervous system during spontaneous healing in both, experimental animals and human patients. We conclude that a closed-loop BMI that defines the optimal stimulation parameters from a priori developed experimental models of the dynamics of spontaneous repair and the on-line monitoring of neural activity might place BMIs as an alternative or complement to stem-cell transplantation or pharmacological approaches, intensively pursued nowadays.

Helsinki Stroke Model Is Transferrable With “Real-World” Resources and Reduced Stroke Thrombolysis Delay to 34 min in Christchurch

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Teddy Y. Wu

2018-04-01

Full Text Available BackgroundChristchurch hospital is a tertiary hospital in New Zealand supported by five general neurologists with after-hours services provided mainly by onsite non-neurology medical residents. We assessed the transferrability and impact of the Helsinki Stroke model on stroke thrombolysis door-to-needle time (DNT in Christchurch hospital.MethodsKey components of the Helsinki Stroke model were implemented first in 2015 with introduction of patient pre-notification and thrombolysis by the computed tomography (CT suite, followed by implementation of direct transfer to CT on ambulance stretcher in May 2017. Data from the prospective thrombolysis registry which began in 2012 were analyzed for the impact of these interventions on median DNT.ResultsBetween May and December 2017, 46 patients were treated with alteplase, 25 (54% patients were treated in-hours (08:00–17:00 non-public holiday weekdays and 21 (46% patients were treated after-hours. The in-hours, after-hours, and overall median (interquartile range DNTs were 34 (28–43, 47 (38–60, and 40 (30–51 minutes. The corresponding times in 2012–2014 prior to interventions were 87 (68–106, 86 (72–116, and 87 (71–112 minutes, representing median DNT reduction of 53, 39, and 47 minutes, respectively (p-values <0.01. The interventions also resulted in significant reductions in the overall median door-to-CT time (from 49 to 19 min, CT-to-needle time (32 to 20 min and onset-to-needle time (168 to 120 min.ConclusionThe Helsinki stroke model is transferrable with real-world resources and reduced stroke DNT in Christchurch by over 50%.

Validation of the Neurological Fatigue Index for stroke (NFI-Stroke

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Mills Roger J

2012-05-01

Full Text Available Abstract Background Fatigue is a common symptom in Stroke. Several self-report scales are available to measure this debilitating symptom but concern has been expressed about their construct validity. Objective To examine the reliability and validity of a recently developed scale for multiple sclerosis (MS fatigue, the Neurological Fatigue Index (NFI-MS, in a sample of stroke patients. Method Six patients with stroke participated in qualitative interviews which were analysed and the themes compared for equivalence to those derived from existing data on MS fatigue. 999 questionnaire packs were sent to those with a stroke within the past four years. Data from the four subscales, and the Summary scale of the NFI-MS were fitted to the Rasch measurement model. Results Themes identified by stroke patients were consistent with those identified by those with MS. 282 questionnaires were returned and respondents had a mean age of 67.3 years; 62% were male, and were on average 17.2 (SD 11.4, range 2–50 months post stroke. The Physical, Cognitive and Summary scales all showed good fit to the model, were unidimensional, and free of differential item functioning by age, sex and time. The sleep scales failed to show adequate fit in their current format. Conclusion Post stroke fatigue appears to be represented by a combination of physical and cognitive components, confirmed by both qualitative and quantitative processes. The NFI-Stroke, comprising a Physical and Cognitive subscale, and a 10-item Summary scale, meets the strictest measurement requirements. Fit to the Rasch model allows conversion of ordinal raw scores to a linear metric.

Pre-stroke use of statins on stroke outcome : a meta-analysis of observational studies

NARCIS (Netherlands)

Cordenier, Ann; De Smedt, Ann; Brouns, Raf; Uyttenboogaart, Maarten; De Raedt, Sylvie; Luijckx, Gert-Jan; De Keyser, Jacques

2011-01-01

Background: Animal pre-clinical studies suggest that statins may have neuroprotective effects in acute ischaemic stroke. Statins might also increase the risk of developing haemorrhagic transformation after thrombolytic treatment. Methods: We performed a systematic review and included studies that

Animal Models for Periodontal Disease

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Helieh S. Oz

2011-01-01

Full Text Available Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed.

Animal Models for Periodontal Disease

Science.gov (United States)

Oz, Helieh S.; Puleo, David A.

2011-01-01

Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis) in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed. PMID:21331345

Evaluation of animal models of neurobehavioral disorders

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Nordquist Rebecca E

2009-02-01

Full Text Available Abstract Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration. Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result. Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia. In a manner congruent to

Animal models.

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Walker, Ellen A

2010-01-01

As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.

Effects of stroke education of junior high school students on stroke knowledge of their parents: Tochigi project.

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Matsuzono, Kosuke; Yokota, Chiaki; Takekawa, Hidehiro; Okamura, Tomonori; Miyamatsu, Naomi; Nakayama, Hirofumi; Nishimura, Kunihiro; Ohyama, Satoshi; Ishigami, Akiko; Okumura, Kosuke; Toyoda, Kazunori; Miyamoto, Yoshihiro; Minematsu, Kazuo

2015-02-01

Educating the youth about stroke is a promising approach for spreading stroke knowledge. The aim of this study was to verify communication of stroke knowledge to parents by educating junior high school students about stroke. We enrolled 1127 junior high school students (age, 13-15 years) and their parents in the Tochigi prefecture, Japan. All students received a stroke lesson, watched an animated cartoon, and read the related Manga comic as educational aids. The students took back home the Manga and discussed what they learned with their parents. Questionnaires on stroke knowledge were given to all at baseline and immediately after the lesson. A total of 1125 students and 915 parents answered the questionnaires. In the students, the frequency of correct answers increased significantly for all questions on stroke symptoms except for headache, and for all questions on risk factors after the lesson. In the parents, the correct answer rates increased for stroke symptoms except for headache and numbness in one side of the body, and for all questions on risk factors except for hypertension. Ninety-one percent of students and 92.7% of parents correctly understood the Face, Arm, Speech, and Time (FAST) mnemonic after the lesson. Improvement of stroke knowledge immediately after the stroke lesson was observed in parents as well as their children, which indicated that our teaching materials using the Manga was effective in delivering the stroke knowledge to parents through their children. © 2014 American Heart Association, Inc.

Effect of Pre-nutrion of Flax Seed Oil (Linum Usitatissimum on the amount of Cerebral ischemic lesion and motor nerve disorders in animal model rat.

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SV Hosseini

2015-10-01

Full Text Available Background & aim: Stroke is the third death agent (factor in industrial countries after cardiovascular disease and cancer. With regard to high content of antioxidant materials in flax seed oil like &alpha-linolenic acid, lignan as well as phenolic combinations like secoisolarisirsinol (SDG, this study performed for studding relationship between of cerebral ischemic lesion and motor-nerve disorders in model of stroke in rat. Methods: in the study, 35 male mice from strain Wistar divided to 5 groups. The groups included control, sham and 3 experimental groups. They received doses 0.25, 0.5 and 0.75 ml/kg from flax seed oil orally. By gavage for 30 days two control and sham groups received aqua distillate (distil water. Two hours after the last gavaged dose, overly group with 7 pieces operated for measurement of the amount of cerebral lesion and motor-nerve disorders. (Middle Cerebral Artery Occlusion Model. Middle cerebral Artery Occlusion by the model resulted in local ischemic stroke in animal. Data analyzed by software SPSS, test ANOVA and disorders by test mann-Whitney. Findings: Average of records of motor-nerve disorders decreased significantly in group with dose 0.5 and 0.75 using flax seed oil (P<0.05. The amount of cerebral ischemic lesion in doses 0.5 and 0.75 than to control group is indicated meaning full different, but percent of the total cerebral lesion in control group in compared group with dose 0.25 is not indicated meaningful different. Percent of the amount of ischemic lesion in region penumbra in group 0.75 and 0.5 than to control group is indicated meaningful different, but percent of the amount of lesion in region penumbra in control group in compared region penumbra in group with dose 0.25 is not indicated meaning full different. Results: Findings of the study indicated that flax seed oil, particular in doses 0.5 and 0.75 resulted to decrease of the amount of cerebral ischemic lesion and decrease of motor-nerve disorders in

Potency of Animal Models in KANSEI Engineering

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Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki

Various species of animals have been used as animal models for neuroscience and provided critical information about the brain functions. Although it seems difficult to elucidate a highly advanced function of the human brain, animal models have potency to clarify the fundamental mechanisms of emotion, decision-making and social behavior. In this review, we will pick up common animal models and point to both the merits and demerits caused by the characteristics. We will also mention that wide-ranging approaches from animal models are advantageous to understand KANSEI as well as mind in humans.

An animal model for tinnitus.

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Jastreboff, P J; Brennan, J F; Sasaki, C T

1988-03-01

Subjective tinnitus remains obscure, widespread, and without apparent cure. In the absence of a suitable animal model, past investigations took place in humans, resulting in studies that were understandably restricted by the nature of human investigation. Within this context, the development of a valid animal model would be considered a major breakthrough in this field of investigation. Our results showed changes in the spontaneous activity of single neurons in the inferior colliculus, consistent with abnormally increased neuronal activity within the auditory pathways after manipulations known to produce tinnitus in man. A procedure based on a Pavlovian conditioned suppression paradigm was recently developed that allows us to measure tinnitus behaviorally in conscious animals. Accordingly, an animal model of tinnitus is proposed that permits tests of hypotheses relating to tinnitus generation, allowing the accommodation of interventional strategies for the treatment of this widespread auditory disorder.

Comprehensive stroke units: a review of comparative evidence and experience.

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Chan, Daniel K Y; Cordato, Dennis; O'Rourke, Fintan; Chan, Daniel L; Pollack, Michael; Middleton, Sandy; Levi, Chris

2013-06-01

Stroke unit care offers significant benefits in survival and dependency when compared to general medical ward. Most stroke units are either acute or rehabilitation, but comprehensive (combined acute and rehabilitation) model (comprehensive stroke unit) is less common. To examine different levels of evidence of comprehensive stroke unit compared to other organized inpatient stroke care and share local experience of comprehensive stroke units. Cochrane Library and Medline (1980 to December 2010) review of English language articles comparing stroke units to alternative forms of stroke care delivery, different types of stroke unit models, and differences in processes of care within different stroke unit models. Different levels of comparative evidence of comprehensive stroke units to other models of stroke units are collected. There are no randomized controlled trials directly comparing comprehensive stroke units to other stroke unit models (either acute or rehabilitation). Comprehensive stroke units are associated with reduced length of stay and greatest reduction in combined death and dependency in a meta-analysis study when compared to other stroke unit models. Comprehensive stroke units also have better length of stay and functional outcome when compared to acute or rehabilitation stroke unit models in a cross-sectional study, and better length of stay in a 'before-and-after' comparative study. Components of stroke unit care that improve outcome are multifactorial and most probably include early mobilization. A comprehensive stroke unit model has been successfully implemented in metropolitan and rural hospital settings. Comprehensive stroke units are associated with reductions in length of stay and combined death and dependency and improved functional outcomes compared to other stroke unit models. A comprehensive stroke unit model is worth considering as the preferred model of stroke unit care in the planning and delivery of metropolitan and rural stroke services

XX. Animal models of pneumocystosis

DEFF Research Database (Denmark)

Dei-Cas, E.; Brun-Pascaud, M.; Bille-Hansen, Vivi

1998-01-01

As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... a source of parasites taxonomically related to P. carinii sp. f hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown......, are important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis...

In-hospital risk prediction for post-stroke depression: development and validation of the Post-stroke Depression Prediction Scale.

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de Man-van Ginkel, Janneke M; Hafsteinsdóttir, Thóra B; Lindeman, Eline; Ettema, Roelof G A; Grobbee, Diederick E; Schuurmans, Marieke J

2013-09-01

The timely detection of post-stroke depression is complicated by a decreasing length of hospital stay. Therefore, the Post-stroke Depression Prediction Scale was developed and validated. The Post-stroke Depression Prediction Scale is a clinical prediction model for the early identification of stroke patients at increased risk for post-stroke depression. The study included 410 consecutive stroke patients who were able to communicate adequately. Predictors were collected within the first week after stroke. Between 6 to 8 weeks after stroke, major depressive disorder was diagnosed using the Composite International Diagnostic Interview. Multivariable logistic regression models were fitted. A bootstrap-backward selection process resulted in a reduced model. Performance of the model was expressed by discrimination, calibration, and accuracy. The model included a medical history of depression or other psychiatric disorders, hypertension, angina pectoris, and the Barthel Index item dressing. The model had acceptable discrimination, based on an area under the receiver operating characteristic curve of 0.78 (0.72-0.85), and calibration (P value of the U-statistic, 0.96). Transforming the model to an easy-to-use risk-assessment table, the lowest risk category (sum score, depression, which increased to 82% in the highest category (sum score, >21). The clinical prediction model enables clinicians to estimate the degree of the depression risk for an individual patient within the first week after stroke.

Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke

NARCIS (Netherlands)

R. Saxena (Ruchi); A.D. Wijnhoud (Annemarie); H. Carton; W. Hacke (Werner); M. Kaste; R.J. Przybelski; K.N. Stern; P.J. Koudstaal (Peter Jan)

1999-01-01

textabstractBACKGROUND AND PURPOSE: Diaspirin cross-linked hemoglobin (DCLHb) is a purified, cell-free human hemoglobin solution. In animal stroke models its use led to a significant reduction in the extent of brain injury. The primary objective of this study was to evaluate the safety of DCLHb in

Intracranial Pressure Elevation 24 Hours after Ischemic Stroke in Aged Rats is Prevented by Early, Short Hypothermia Treatment

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Lucy Anne Murtha

2016-05-01

Full Text Available Stroke is predominantly a senescent disease, yet most preclinical studies investigate treatment in young animals. We recently demonstrated that short-duration hypothermia-treatment completely prevented the dramatic intracranial pressure (ICP rise seen post-stroke in young rats. Here, our aim was to investigate whether a similar ICP rise occurs in aged rats and to determine whether short-duration hypothermia is an effective treatment in aged animals. Experimental Middle Cerebral Artery occlusion (MCAo - 3 hour occlusion was performed on male Wistar rats aged 19-20 months. At one hour after stroke-onset, rats were randomized to 2.5 hours hypothermia-treatment (32.5 °C or normothermia (37 °C. ICP was monitored at baseline, for 3.5 hours post-occlusion, and at 24 hours post-stroke. Infarct and edema volumes were calculated from histology. Baseline pre-stroke ICP was 11.2 ± 3.3 mmHg across all animals. Twenty-four hours post-stroke, ICP was significantly higher in normothermic animals compared to hypothermia-treated animals (27.4 ± 18.2 mmHg vs. 8.0 ± 5.0 mmHg, p = 0.03. Infarct and edema volumes were not significantly different between groups. These data demonstrate ICP may also increase 24 hours post-stroke in aged rats, and that short-duration hypothermia treatment has a profound and sustained preventative effect. These findings may have important implications for the use of hypothermia in clinical trials of aged stroke patients.

Aging alters the immunological response to ischemic stroke.

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Ritzel, Rodney M; Lai, Yun-Ju; Crapser, Joshua D; Patel, Anita R; Schrecengost, Anna; Grenier, Jeremy M; Mancini, Nickolas S; Patrizz, Anthony; Jellison, Evan R; Morales-Scheihing, Diego; Venna, Venugopal R; Kofler, Julia K; Liu, Fudong; Verma, Rajkumar; McCullough, Louise D

2018-05-11

The peripheral immune system plays a critical role in aging and in the response to brain injury. Emerging data suggest inflammatory responses are exacerbated in older animals following ischemic stroke; however, our understanding of these age-related changes is poor. In this work, we demonstrate marked differences in the composition of circulating and infiltrating leukocytes recruited to the ischemic brain of old male mice after stroke compared to young male mice. Blood neutrophilia and neutrophil invasion into the brain were increased in aged animals. Relative to infiltrating monocyte populations, brain-invading neutrophils had reduced phagocytic potential, and produced higher levels of reactive oxygen species and extracellular matrix-degrading enzymes (i.e., MMP-9), which were further exacerbated with age. Hemorrhagic transformation was more pronounced in aged versus young mice relative to infarct size. High numbers of myeloperoxidase-positive neutrophils were found in postmortem human brain samples of old (> 71 years) acute ischemic stroke subjects compared to non-ischemic controls. Many of these neutrophils were found in the brain parenchyma. A large proportion of these neutrophils expressed MMP-9 and positively correlated with hemorrhage and hyperemia. MMP-9 expression and hemorrhagic transformation after stroke increased with age. These changes in the myeloid response to stroke with age led us to hypothesize that the bone marrow response to stroke is altered with age, which could be important for the development of effective therapies targeting the immune response. We generated heterochronic bone marrow chimeras as a tool to determine the contribution of peripheral immune senescence to age- and stroke-induced inflammation. Old hosts that received young bone marrow (i.e., Young → Old) had attenuation of age-related reductions in bFGF and VEGF and showed improved locomotor activity and gait dynamics compared to isochronic (Old → Old) controls

[Application of Competing Risks Model in Predicting Smoking Relapse Following Ischemic Stroke].

Science.gov (United States)

Hou, Li-Sha; Li, Ji-Jie; Du, Xu-Dong; Yan, Pei-Jing; Zhu, Cai-Rong

2017-07-01

To determine factors associated with smoking relapse in men who survived from their first stroke. Data were collected through face to face interviews with stroke patients in the hospital, and then repeated every three months via telephone over the period from 2010 to 2014. Kaplan-Meier method and competing risk model were adopted to estimate and predict smoking relapse rates. The Kaplan-Meier method estimated a higher relapse rate than the competing risk model. The four-year relapse rate was 43.1% after adjustment of competing risk. Exposure to environmental tobacco smoking outside of home and workplace (such as bars and restaurants) ( P =0.01), single ( P <0.01), and prior history of smoking at least 20 cigarettes per day ( P =0.02) were significant predictors of smoking relapse. When competing risks exist, competing risks model should be used in data analyses. Smoking interventions should give priorities to those without a spouse and those with a heavy smoking history. Smoking ban in public settings can reduce smoking relapse in stroke patients.

Stroke risk perception among participants of a stroke awareness campaign

Science.gov (United States)

Kraywinkel, Klaus; Heidrich, Jan; Heuschmann, Peter U; Wagner, Markus; Berger, Klaus

2007-01-01

Background Subjective risk factor perception is an important component of the motivation to change unhealthy life styles. While prior studies assessed cardiovascular risk factor knowledge, little is known about determinants of the individual perception of stroke risk. Methods Survey by mailed questionnaire among 1483 participants of a prior public stroke campaign in Germany. Participants had been informed about their individual stroke risk based on the Framingham stroke risk score. Stroke risk factor knowledge, perception of lifetime stroke risk and risk factor status were included in the questionnaire, and the determinants of good risk factor knowledge and high stroke risk perception were identified using logistic regression models. Results Overall stroke risk factor knowledge was good with 67–96% of the participants recognizing established risk factors. The two exceptions were diabetes (recognized by 49%) and myocardial infarction (57%). Knowledge of a specific factor was superior among those affected by it. 13% of all participants considered themselves of having a high stroke risk, 55% indicated a moderate risk. All major risk factors contributed significantly to the perception of being at high stroke risk, but the effects of age, sex and education were non-significant. Poor self-rated health was additionally associated with high individual stroke risk perception. Conclusion Stroke risk factor knowledge was high in this study. The self perception of an increased stroke risk was associated with established risk factors as well as low perception of general health. PMID:17371603

Rose Bengal Photothrombosis by Confocal Optical Imaging In Vivo: A Model of Single Vessel Stroke.

Science.gov (United States)

Talley Watts, Lora; Zheng, Wei; Garling, R Justin; Frohlich, Victoria C; Lechleiter, James Donald

2015-06-23

In vivo imaging techniques have increased in utilization due to recent advances in imaging dyes and optical technologies, allowing for the ability to image cellular events in an intact animal. Additionally, the ability to induce physiological disease states such as stroke in vivo increases its utility. The technique described herein allows for physiological assessment of cellular responses within the CNS following a stroke and can be adapted for other pathological conditions being studied. The technique presented uses laser excitation of the photosensitive dye Rose Bengal in vivo to induce a focal ischemic event in a single blood vessel. The video protocol demonstrates the preparation of a thin-skulled cranial window over the somatosensory cortex in a mouse for the induction of a Rose Bengal photothrombotic event keeping injury to the underlying dura matter and brain at a minimum. Surgical preparation is initially performed under a dissecting microscope with a custom-made surgical/imaging platform, which is then transferred to a confocal microscope equipped with an inverted objective adaptor. Representative images acquired utilizing this protocol are presented as well as time-lapse sequences of stroke induction. This technique is powerful in that the same area can be imaged repeatedly on subsequent days facilitating longitudinal in vivo studies of pathological processes following stroke.

Development and validation of clinical prediction models for mortality, functional outcome and cognitive impairment after stroke: a study protocol.

Science.gov (United States)

Fahey, Marion; Rudd, Anthony; Béjot, Yannick; Wolfe, Charles; Douiri, Abdel

2017-08-18

Stroke is a leading cause of adult disability and death worldwide. The neurological impairments associated with stroke prevent patients from performing basic daily activities and have enormous impact on families and caregivers. Practical and accurate tools to assist in predicting outcome after stroke at patient level can provide significant aid for patient management. Furthermore, prediction models of this kind can be useful for clinical research, health economics, policymaking and clinical decision support. 2869 patients with first-ever stroke from South London Stroke Register (SLSR) (1995-2004) will be included in the development cohort. We will use information captured after baseline to construct multilevel models and a Cox proportional hazard model to predict cognitive impairment, functional outcome and mortality up to 5 years after stroke. Repeated random subsampling validation (Monte Carlo cross-validation) will be evaluated in model development. Data from participants recruited to the stroke register (2005-2014) will be used for temporal validation of the models. Data from participants recruited to the Dijon Stroke Register (1985-2015) will be used for external validation. Discrimination, calibration and clinical utility of the models will be presented. Patients, or for patients who cannot consent their relatives, gave written informed consent to participate in stroke-related studies within the SLSR. The SLSR design was approved by the ethics committees of Guy's and St Thomas' NHS Foundation Trust, Kings College Hospital, Queens Square and Westminster Hospitals (London). The Dijon Stroke Registry was approved by the Comité National des Registres and the InVS and has authorisation of the Commission Nationale de l'Informatique et des Libertés. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Animal models for rotator cuff repair.

Science.gov (United States)

Lebaschi, Amir; Deng, Xiang-Hua; Zong, Jianchun; Cong, Guang-Ting; Carballo, Camila B; Album, Zoe M; Camp, Christopher; Rodeo, Scott A

2016-11-01

Rotator cuff (RC) injuries represent a significant source of pain, functional impairment, and morbidity. The large disease burden of RC pathologies necessitates rapid development of research methodologies to treat these conditions. Given their ability to model anatomic, biomechanical, cellular, and molecular aspects of the human RC, animal models have played an indispensable role in reducing injury burden and advancing this field of research for many years. The development of animal models in the musculoskeletal (MSK) research arena is uniquely different from that in other fields in that the similarity of macrostructures and functions is as critical to replicate as cellular and molecular functions. Traditionally, larger animals have been used because of their anatomic similarity to humans and the ease of carrying out realistic surgical procedures. However, refinement of current molecular methods, introduction of novel research tools, and advancements in microsurgical techniques have increased the applicability of small animal models in MSK research. In this paper, we review RC animal models and emphasize a murine model that may serve as a valuable instrument for future RC tendon repair investigations. © 2016 New York Academy of Sciences.

Greater stroke severity predominates over all other factors for the worse outcome of cardioembolic stroke.

Science.gov (United States)

Hong, Keun-Sik; Lee, Juneyoung; Bae, Hee-Joon; Lee, Ji Sung; Kang, Dong-Wha; Yu, Kyung-Ho; Han, Moon-Ku; Cho, Yong-Jin; Song, Pamela; Park, Jong-Moo; Oh, Mi-Sun; Koo, Jaseong; Lee, Byung-Chul

2013-11-01

Cardioembolic (CE) strokes are more disabling and more fatal than non-CE strokes. Multiple prognostic factors have been recognized, but the magnitude of their relative contributions has not been well explored. Using a prospective stroke outcome database, we compared the 3-month outcomes of CE and non-CE strokes. We assessed the relative contribution of each prognostic factor of initial stroke severity, poststroke complications, and baseline characteristics with multivariable analyses and model fitness improvement using -2 log-likelihood and Nagelkerke R2. This study included 1233 patients with acute ischemic stroke: 193 CE strokes and 1040 non-CE strokes. Compared with the non-CE group, CE group had less modified Rankin Scale (mRS) 0-2 outcomes (47.2% versus 68.5%; odds ratio [95% confidence interval], .41 [.30-.56]), less mRS 0-1 outcomes (33.7% versus 53.5%; .44 [.32-.61]), more mRS 5-6 outcomes (32.1% versus 10.9%; 3.88 [2.71-5.56]), and higher mortality (19.2% versus 5.2%; 4.33 [2.76-6.80]) at 3 months. When adjusting either baseline characteristics or poststroke complications, the outcome differences between the 2 groups remained significant. However, adjusting initial National Institute of Health Stroke Scale (NIHSS) score alone abolished all outcome differences except for mortality. For mRS 0-2 outcomes, the decrement of -2 log-likelihood and the Nagelkerke R2 of the model adjusting initial NIHSS score alone approached 70.2% and 76.7% of the fully adjusting model. Greater stroke severity predominates over all other factors for the worse outcome of CE stroke. Primary prevention and more efficient acute therapy for stroke victims should be given top priorities to reduce the burden of CE strokes. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Immunomodulators and microRNAs as neurorestorative therapy for ischemic stroke

Directory of Open Access Journals (Sweden)

Bridget Martinez

2017-01-01

Full Text Available Most of all strokes are ischemic due to occlusion of a vessel, and comprise two main types, thrombotic and embolic. Inflammation and immune response play an important role in the outcome of ischemic stroke. Pharmaceutical and cell-based therapies with immunomodulatory properties could be of benefit in treating ischemic stroke. Possible changes in microRNAs brought about by immunomodulatory treatments may be important. The pharmaceutical studies described in this review have identified several differentially regulated miRNAs associated with disregulation of mRNA targets or the upregulation of several neuroprotective genes, thereby highlighting the potential neuroprotective roles of specific miRNAs such as miR-762, -1892, -200a, -145. MiR-124, -711, -145 are the strongly associated miRNAs predicted to mediate anti-inflammatory pathways and microglia/macrophage M2-like activation phenotype. The cell-based therapy studies reviewed have mainly utilized mesenchymal stem cells or human umbilical cord blood cells and shown to improve functional and neurological outcomes in stroke animals. MiR-145 and miR-133b were implicated in nerve cell remodeling and functional recovery after stroke. Human umbilical cord blood cells decreased proinflammatory factors and promoted M2 macrophage polarization in stroke diabetic animals.

Animal models of cardiovascular diseases.

Science.gov (United States)

Zaragoza, Carlos; Gomez-Guerrero, Carmen; Martin-Ventura, Jose Luis; Blanco-Colio, Luis; Lavin, Begoña; Mallavia, Beñat; Tarin, Carlos; Mas, Sebastian; Ortiz, Alberto; Egido, Jesus

2011-01-01

Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.

Derivation and external validation of a case mix model for the standardized reporting of 30-day stroke mortality rates.

Science.gov (United States)

Bray, Benjamin D; Campbell, James; Cloud, Geoffrey C; Hoffman, Alex; James, Martin; Tyrrell, Pippa J; Wolfe, Charles D A; Rudd, Anthony G

2014-11-01

Case mix adjustment is required to allow valid comparison of outcomes across care providers. However, there is a lack of externally validated models suitable for use in unselected stroke admissions. We therefore aimed to develop and externally validate prediction models to enable comparison of 30-day post-stroke mortality outcomes using routine clinical data. Models were derived (n=9000 patients) and internally validated (n=18 169 patients) using data from the Sentinel Stroke National Audit Program, the national register of acute stroke in England and Wales. External validation (n=1470 patients) was performed in the South London Stroke Register, a population-based longitudinal study. Models were fitted using general estimating equations. Discrimination and calibration were assessed using receiver operating characteristic curve analysis and correlation plots. Two final models were derived. Model A included age (<60, 60-69, 70-79, 80-89, and ≥90 years), National Institutes of Health Stroke Severity Score (NIHSS) on admission, presence of atrial fibrillation on admission, and stroke type (ischemic versus primary intracerebral hemorrhage). Model B was similar but included only the consciousness component of the NIHSS in place of the full NIHSS. Both models showed excellent discrimination and calibration in internal and external validation. The c-statistics in external validation were 0.87 (95% confidence interval, 0.84-0.89) and 0.86 (95% confidence interval, 0.83-0.89) for models A and B, respectively. We have derived and externally validated 2 models to predict mortality in unselected patients with acute stroke using commonly collected clinical variables. In settings where the ability to record the full NIHSS on admission is limited, the level of consciousness component of the NIHSS provides a good approximation of the full NIHSS for mortality prediction. © 2014 American Heart Association, Inc.

Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors.

Science.gov (United States)

Andersen, Klaus Kaae; Olsen, Tom Skyhøj; Dehlendorff, Christian; Kammersgaard, Lars Peter

2009-06-01

Stroke patients with hemorrhagic (HS) and ischemic strokes were compared with regard to stroke severity, mortality, and cardiovascular risk factors. A registry started in 2001, with the aim of registering all hospitalized stroke patients in Denmark, now holds information for 39,484 patients. The patients underwent an evaluation including stroke severity (Scandinavian Stroke Scale), CT, and cardiovascular risk factors. They were followed-up from admission until death or censoring in 2007. Independent predictors of death were identified by means of a survival model based on 25,123 individuals with a complete data set. Of the patients 3993 (10.1%) had HS. Stroke severity was almost linearly related to the probability of having HS (2% in patients with the mildest stroke and 30% in those with the most severe strokes). Factors favoring ischemic strokes vs HS were diabetes, atrial fibrillation, previous myocardial infarction, previous stroke, and intermittent arterial claudication. Smoking and alcohol consumption favored HS, whereas age, sex, and hypertension did not herald stroke type. Compared with ischemic strokes, HS was associated with an overall higher mortality risk (HR, 1.564; 95% CI, 1.441-1.696). The increased risk was, however, time-dependent; initially, risk was 4-fold, after 1 week it was 2.5-fold, and after 3 weeks it was 1.5-fold. After 3 months stroke type did not correlate to mortality. Strokes are generally more severe in patients with HS. Within the first 3 months after stroke, HS is associated with a considerable increase of mortality, which is specifically associated with the hemorrhagic nature of the lesion.

External Validation of a Case-Mix Adjustment Model for the Standardized Reporting of 30-Day Stroke Mortality Rates in China.

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Yu, Ping; Pan, Yuesong; Wang, Yongjun; Wang, Xianwei; Liu, Liping; Ji, Ruijun; Meng, Xia; Jing, Jing; Tong, Xu; Guo, Li; Wang, Yilong

2016-01-01

A case-mix adjustment model has been developed and externally validated, demonstrating promise. However, the model has not been thoroughly tested among populations in China. In our study, we evaluated the performance of the model in Chinese patients with acute stroke. The case-mix adjustment model A includes items on age, presence of atrial fibrillation on admission, National Institutes of Health Stroke Severity Scale (NIHSS) score on admission, and stroke type. Model B is similar to Model A but includes only the consciousness component of the NIHSS score. Both model A and B were evaluated to predict 30-day mortality rates in 13,948 patients with acute stroke from the China National Stroke Registry. The discrimination of the models was quantified by c-statistic. Calibration was assessed using Pearson's correlation coefficient. The c-statistic of model A in our external validation cohort was 0.80 (95% confidence interval, 0.79-0.82), and the c-statistic of model B was 0.82 (95% confidence interval, 0.81-0.84). Excellent calibration was reported in the two models with Pearson's correlation coefficient (0.892 for model A, pcase-mix adjustment model could be used to effectively predict 30-day mortality rates in Chinese patients with acute stroke.

Cerebrolysin and aquaporin 4 inhibition improve pathological and motor recovery after ischemic stroke.

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Catalin, Bogdan; Rogoveanu, O C; Pirici, Ionica; Balseanu, Tudor Adrian; Stan, Adina; Tudorica, Valerica; Balea, Maria; Mindrila, Ion; Albu, Carmen Valeria; Mohamed, Guleed; Pirici, Daniel; Muresanu, Dafin Fior

2018-04-25

Edema represents one of the earliest negative markers of survival and consecutive neurological deficit following stroke. The mixture of cellular and vasogenic edema makes treating this condition complicated, and to date, there is no pathogenically oriented drug treatment for edema, which leaves parenteral administration of a hypertonic solution as the only non-surgical alternative. New insights into water metabolism in the brain have opened the way for molecular targeted treatment, with aquaporin 4 channels (AQP4) taking center stage. We aimed here to assess the effect of inhibiting AQP4 together with the administration of a neurotropic factor (Cerebrolysin) in ischemic stroke. Using a permanent medial cerebral artery occlusion rat model, we administrated a single dose of the AQP4 inhibitor TGN-020 (100 mg/kg) at 15 minutes after ischemia followed by daily Cerebrolysin dosing (5ml/kg) for seven days. Rotarod motor testing and neuropathology examinations were next performed. We showed first that the combination treatment animals have a better motor function preservation at seven days after permanent ischemia. We have also identified distinct cellular contributions that represent the bases of behavior testing, such as less astrocyte scarring and a larger neuronal-survival phenotype rate in animals treated with both compounds than in animals treated with Cerebrolysin alone or untreated animals. Our data shows that water diffusion inhibition and Cerebrolysin administration after focal ischemic stroke reduces infarct size, leading to a higher neuronal survival in the peri-core glial scar region. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Animal models for testing anti-prion drugs.

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Fernández-Borges, Natalia; Elezgarai, Saioa R; Eraña, Hasier; Castilla, Joaquín

2013-01-01

Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence of different animal models for testing anti-prion compounds. Wild type, over-expressing transgenic mice and other more sophisticated animal models have been used to evaluate a diversity of compounds which some of them were previously tested in different in vitro experimental models. The complexity of prion diseases will require more pre-screening studies, reliable sporadic (or spontaneous) animal models and accurate chemical modifications of the selected compounds before having an effective therapy against human prion diseases. This review is intended to put on display the more relevant animal models that have been used in the search of new antiprion therapies and describe some possible procedures when handling chemical compounds presumed to have anti-prion activity prior to testing them in animal models.

Stroke: advances in medical therapy and acute stroke intervention.

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Barrett, Kevin M; Lal, Brajesh K; Meschia, James F

2015-10-01

Evidence-based therapeutic options for stroke continue to emerge based on results from well-designed clinical studies. Ischemic stroke far exceeds hemorrhagic stroke in terms of prevalence and incidence, both in the USA and worldwide. The public health effect of reducing death and disability related to ischemic stroke justifies the resources that have been invested in identifying safe and effective treatments. The emergence of novel oral anticoagulants for ischemic stroke prevention in atrial fibrillation has introduced complexity to clinical decision making for patients with this common cardiac arrhythmia. Some accepted ischemic stroke preventative strategies, such as carotid revascularization for asymptomatic carotid stenosis, require reassessment, given advances in risk factor management, antithrombotic therapy, and surgical techniques. Intra-arterial therapy, particularly with stent retrievers after intravenous tissue plasminogen activator, has recently been demonstrated to improve functional outcomes and will require investment in system-based care models to ensure that effective treatments are received by patients in a timely fashion. The purpose of this review is to describe recent advances in medical and surgical approaches to ischemic stroke prevention and acute treatment. Results from recently published clinical trials will be highlighted along with ongoing clinical trials addressing key questions in ischemic stroke management and prevention where equipoise remains.

Animal Models of Hemophilia

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Sabatino, Denise E.; Nichols, Timothy C.; Merricks, Elizabeth; Bellinger, Dwight A.; Herzog, Roland W.; Monahan, Paul E.

2013-01-01

The X-linked bleeding disorder hemophilia is caused by mutations in coagulation factor VIII (hemophilia A) or factor IX (hemophilia B). Unless prophylactic treatment is provided, patients with severe disease (less than 1% clotting activity) typically experience frequent spontaneous bleeds. Current treatment is largely based on intravenous infusion of recombinant or plasma-derived coagulation factor concentrate. More effective factor products are being developed. Moreover, gene therapies for sustained correction of hemophilia are showing much promise in pre-clinical studies and in clinical trials. These advances in molecular medicine heavily depend on availability of well-characterized small and large animal models of hemophilia, primarily hemophilia mice and dogs. Experiments in these animals represent important early and intermediate steps of translational research aimed at development of better and safer treatments for hemophilia, such a protein and gene therapies or immune tolerance protocols. While murine models are excellent for studies of large groups of animals using genetically defined strains, canine models are important for testing scale-up and for longer-term follow-up as well as for studies that require larger blood volumes. PMID:22137432

Animal models of exercise and obesity.

Science.gov (United States)

Kasper, Christine E

2013-01-01

Animal models have been invaluable in the conduct of nursing research for the past 40 years. This review will focus on specific animal models that can be used in nursing research to study the physiologic phenomena of exercise and obesity when the use of human subjects is either scientifically premature or inappropriate because of the need for sampling tissue or the conduct of longitudinal studies of aging. There exists an extensive body of literature reporting the experimental use of various animal models, in both exercise science and the study of the mechanisms of obesity. Many of these studies are focused on the molecular and genetic mechanisms of organ system adaptation and plasticity in response to exercise, obesity, or both. However, this review will narrowly focus on the models useful to nursing research in the study of exercise in the clinical context of increasing performance and mobility, atrophy and bedrest, fatigue, and aging. Animal models of obesity focus on those that best approximate clinical pathology.

External Validation of a Case-Mix Adjustment Model for the Standardized Reporting of 30-Day Stroke Mortality Rates in China.

Directory of Open Access Journals (Sweden)

Ping Yu

Full Text Available A case-mix adjustment model has been developed and externally validated, demonstrating promise. However, the model has not been thoroughly tested among populations in China. In our study, we evaluated the performance of the model in Chinese patients with acute stroke.The case-mix adjustment model A includes items on age, presence of atrial fibrillation on admission, National Institutes of Health Stroke Severity Scale (NIHSS score on admission, and stroke type. Model B is similar to Model A but includes only the consciousness component of the NIHSS score. Both model A and B were evaluated to predict 30-day mortality rates in 13,948 patients with acute stroke from the China National Stroke Registry. The discrimination of the models was quantified by c-statistic. Calibration was assessed using Pearson's correlation coefficient.The c-statistic of model A in our external validation cohort was 0.80 (95% confidence interval, 0.79-0.82, and the c-statistic of model B was 0.82 (95% confidence interval, 0.81-0.84. Excellent calibration was reported in the two models with Pearson's correlation coefficient (0.892 for model A, p<0.001; 0.927 for model B, p = 0.008.The case-mix adjustment model could be used to effectively predict 30-day mortality rates in Chinese patients with acute stroke.

Animal Models of Cardiovascular Diseases

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Carlos Zaragoza

2011-01-01

Full Text Available Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.

A Comparison of Different Engineering Models for Computation of Lightning Magnetic Field of Negative First Strokes

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V. Javor

2012-11-01

Full Text Available A comparison of different engineering models results for a lightning magnetic field of negative first strokes is presented in this paper. A new function for representing double-peaked channel-base current is used for lightning stroke modeling. This function includes the initial and subsidiary peak in a current waveform. For experimentally measured currents, a magnetic field is calculated for the three engineering models: transmission line (TL model, TL model with linear decay (MTLL, and TL model with exponential decay (MTLE.

Dynamic Variables Fail to Predict Fluid Responsiveness in an Animal Model With Pericardial Effusion.

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Broch, Ole; Renner, Jochen; Meybohm, Patrick; Albrecht, Martin; Höcker, Jan; Haneya, Assad; Steinfath, Markus; Bein, Berthold; Gruenewald, Matthias

2016-10-01

The reliability of dynamic and volumetric variables of fluid responsiveness in the presence of pericardial effusion is still elusive. The aim of the present study was to investigate their predictive power in a porcine model with hemodynamic relevant pericardial effusion. A single-center animal investigation. Twelve German domestic pigs. Pigs were studied before and during pericardial effusion. Instrumentation included a pulmonary artery catheter and a transpulmonary thermodilution catheter in the femoral artery. Hemodynamic variables like cardiac output (COPAC) and stroke volume (SVPAC) derived from pulmonary artery catheter, global end-diastolic volume (GEDV), stroke volume variation (SVV), and pulse-pressure variation (PPV) were obtained. At baseline, SVV, PPV, GEDV, COPAC, and SVPAC reliably predicted fluid responsiveness (area under the curve 0.81 [p = 0.02], 0.82 [p = 0.02], 0.74 [p = 0.07], 0.74 [p = 0.07], 0.82 [p = 0.02]). After establishment of pericardial effusion the predictive power of dynamic variables was impaired and only COPAC and SVPAC and GEDV allowed significant prediction of fluid responsiveness (area under the curve 0.77 [p = 0.04], 0.76 [p = 0.05], 0.83 [p = 0.01]) with clinically relevant changes in threshold values. In this porcine model, hemodynamic relevant pericardial effusion abolished the ability of dynamic variables to predict fluid responsiveness. COPAC, SVPAC, and GEDV enabled prediction, but their threshold values were significantly changed. Copyright © 2016 Elsevier Inc. All rights reserved.

Animal models: an important tool in mycology.

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Capilla, Javier; Clemons, Karl V; Stevens, David A

2007-12-01

Animal models of fungal infections are, and will remain, a key tool in the advancement of the medical mycology. Many different types of animal models of fungal infection have been developed, with murine models the most frequently used, for studies of pathogenesis, virulence, immunology, diagnosis, and therapy. The ability to control numerous variables in performing the model allows us to mimic human disease states and quantitatively monitor the course of the disease. However, no single model can answer all questions and different animal species or different routes of infection can show somewhat different results. Thus, the choice of which animal model to use must be made carefully, addressing issues of the type of human disease to mimic, the parameters to follow and collection of the appropriate data to answer those questions being asked. This review addresses a variety of uses for animal models in medical mycology. It focuses on the most clinically important diseases affecting humans and cites various examples of the different types of studies that have been performed. Overall, animal models of fungal infection will continue to be valuable tools in addressing questions concerning fungal infections and contribute to our deeper understanding of how these infections occur, progress and can be controlled and eliminated.

Animal Models of Calcific Aortic Valve Disease

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Krista L. Sider

2011-01-01

Full Text Available Calcific aortic valve disease (CAVD, once thought to be a degenerative disease, is now recognized to be an active pathobiological process, with chronic inflammation emerging as a predominant, and possibly driving, factor. However, many details of the pathobiological mechanisms of CAVD remain to be described, and new approaches to treat CAVD need to be identified. Animal models are emerging as vital tools to this end, facilitated by the advent of new models and improved understanding of the utility of existing models. In this paper, we summarize and critically appraise current small and large animal models of CAVD, discuss the utility of animal models for priority CAVD research areas, and provide recommendations for future animal model studies of CAVD.

CCD-camera-based diffuse optical tomography to study ischemic stroke in preclinical rat models

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Lin, Zi-Jing; Niu, Haijing; Liu, Yueming; Su, Jianzhong; Liu, Hanli

2011-02-01

Stroke, due to ischemia or hemorrhage, is the neurological deficit of cerebrovasculature and is the third leading cause of death in the United States. More than 80 percent of stroke patients are ischemic stroke due to blockage of artery in the brain by thrombosis or arterial embolism. Hence, development of an imaging technique to image or monitor the cerebral ischemia and effect of anti-stoke therapy is more than necessary. Near infrared (NIR) optical tomographic technique has a great potential to be utilized as a non-invasive image tool (due to its low cost and portability) to image the embedded abnormal tissue, such as a dysfunctional area caused by ischemia. Moreover, NIR tomographic techniques have been successively demonstrated in the studies of cerebro-vascular hemodynamics and brain injury. As compared to a fiberbased diffuse optical tomographic system, a CCD-camera-based system is more suitable for pre-clinical animal studies due to its simpler setup and lower cost. In this study, we have utilized the CCD-camera-based technique to image the embedded inclusions based on tissue-phantom experimental data. Then, we are able to obtain good reconstructed images by two recently developed algorithms: (1) depth compensation algorithm (DCA) and (2) globally convergent method (GCM). In this study, we will demonstrate the volumetric tomographic reconstructed results taken from tissuephantom; the latter has a great potential to determine and monitor the effect of anti-stroke therapies.

Animal models of attention-deficit hyperactivity disorder

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Sagvolden Terje

2005-07-01

Full Text Available Abstract Although animals cannot be used to study complex human behaviour such as language, they do have similar basic functions. In fact, human disorders that have animal models are better understood than disorders that do not. ADHD is a heterogeneous disorder. The relatively simple nervous systems of rodent models have enabled identification of neurobiological changes that underlie certain aspects of ADHD behaviour. Several animal models of ADHD suggest that the dopaminergic system is functionally impaired. Some animal models have decreased extracellular dopamine concentrations and upregulated postsynaptic dopamine D1 receptors (DRD1 while others have increased extracellular dopamine concentrations. In the latter case, dopamine pathways are suggested to be hyperactive. However, stimulus-evoked release of dopamine is often decreased in these models, which is consistent with impaired dopamine transmission. It is possible that the behavioural characteristics of ADHD result from impaired dopamine modulation of neurotransmission in cortico-striato-thalamo-cortical circuits. There is considerable evidence to suggest that the noradrenergic system is poorly controlled by hypofunctional α2-autoreceptors in some models, giving rise to inappropriately increased release of norepinephrine. Aspects of ADHD behaviour may result from an imbalance between increased noradrenergic and decreased dopaminergic regulation of neural circuits that involve the prefrontal cortex. Animal models of ADHD also suggest that neural circuits may be altered in the brains of children with ADHD. It is therefore of particular importance to study animal models of the disorder and not normal animals. Evidence obtained from animal models suggests that psychostimulants may not be acting on the dopamine transporter to produce the expected increase in extracellular dopamine concentration in ADHD. There is evidence to suggest that psychostimulants may decrease motor activity by

Measuring of vertical stroke Vub vertical stroke in the forthcoming decade

International Nuclear Information System (INIS)

Kim, C.S.

1997-01-01

I first introduce the importance of measuring V ub precisely. Then, from a theoretician's point of view, I review (a) past history, (b) present trials, and (c) possible future alternatives on measuring vertical stroke V ub vertical stroke and/or vertical stroke V ub /V cb vertical stroke. As of my main topic, I introduce a model-independent method, which predicts Γ(B→X u lν)/Γ(B→X c lν)≡(γ u /γ c ) x vertical stroke V ub /V cb vertical stroke 2 ≅(1.83±0.28) x vertical stroke V ub /V cb vertical stroke 2 and vertical stroke V ub /V cb vertical stroke ≡(γ c /γ u ) 1/2 x [B(B→X u lν)/B(B→ X c lν]) 1/2 ≅(0.74±0.06) x [B(B→X u lν/)B(B→X c lν)] 1/2 , based on the heavy quark effective theory I also explore the possible experimental options to separate B→X u lν from the dominant B→X c lν: the measurement of inclusive hadronic invariant mass distributions, and the 'D-π' (and 'K-π') separation conditions I also clarify the relevant experimental backgrounds. (orig.)

Regulation of Hypertension for Secondary Prevention of Stroke: The Possible 'Bridging Function' of Acupuncture.

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Zheng, Haizhen; Han, Yuhui; Du, Yuzheng; Shi, Xuemin; Huang, Huiyuan; Yu, Xiaoyang; Tan, Xiaochan; Hu, Chunxiao; Wang, Yue; Zhou, Shiyuan

2018-01-01

Worldwide, stroke is the leading cause of mortality and disability, with hypertension being an independent risk factor for a secondary stroke. Acupuncture for the treatment of hypertension gains more attention in alternative and complementary medicine, but the results are inconsistent. Few studies regarding the secondary prevention of stroke by managing hypertension with acupuncture have been carried out as there are some problems regarding the antihypertensive drug status in the secondary prevention of stroke. Still, the potential of acupuncture in regulating the blood pressure for secondary stroke prevention deserves our focus. This review is based on papers recorded in the PubMed, Embase, and Web of Science databases, from their inception until March 28, 2017, and retrieved with the following search terms: hypertension and acupuncture, limited in spontaneously hypertensive rats (SHRs), stress-induced (or cold-induced) hypertensive or pre-hypertensive models. We find that, in these hypertensive animals, acupuncture could mainly influence factors related to the nervous system, oxidative stress, the endocrine system, cardiovascular function, and hemorheology, which are closely associated with the stroke outcome. This trend may give us a hint that acupuncture might well participate in the secondary prevention of stroke through these pathways when used in the management of hypertension. © 2018 S. Karger GmbH, Freiburg.

Stroke and Drug Delivery--In Vitro Models of the Ischemic Blood-Brain Barrier

DEFF Research Database (Denmark)

Tornabene, Erica; Brodin, Birger

2016-01-01

of permeation pathways across the barrier in ischemic and postischemic brain endothelium is important for development of new medical treatments. The blood-brain barrier, that is, the endothelial monolayer lining the brain capillaries, changes properties during an ischemic event. In vitro models of the blood-brain......Stroke is a major cause of death and disability worldwide. Both cerebral hypoperfusion and focal cerebral infarcts are caused by a reduction of blood flow to the brain, leading to stroke and subsequent brain damage. At present, only few medical treatments of stroke are available, with the Food...... and Drug Administration-approved tissue plasminogen activator for treatment of acute ischemic stroke being the most prominent example. A large number of potential drug candidates for treatment of ischemic brain tissue have been developed and subsequently failed in clinical trials. A deeper understanding...

Demethylation of Circulating Estrogen Receptor Alpha Gene in Cerebral Ischemic Stroke.

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Hsiu-Fen Lin

Full Text Available Estrogen is involved in neuron plasticity and can promote neuronal survival in stroke. Its actions are mostly exerted via estrogen receptor alpha (ERα. Previous animal studies have shown that ERα is upregulated by DNA demethylation following ischemic injury. This study investigated the methylation levels in the ERα promoter in the peripheral blood of ischemic stroke patients.The study included 201 ischemic stroke patients, and 217 age- and sex-comparable healthy controls. The quantitative methylation level in the 14 CpG sites of the ERα promoter was measured by pyrosequencing in each participant. Multivariate regression model was used to adjust for stroke traditional risk factors. Stroke subtypes and sex-specific analysis were also conducted.The results demonstrated that the stroke cases had a lower ERα methylation level than controls in all 14 CpG sites, and site 13 and site 14 had significant adjusted p-values of 0.035 and 0.026, respectively. Stroke subtypes analysis showed that large-artery atherosclerosis and cardio-embolic subtypes had significantly lower methylation levels than the healthy controls at CpG site 5, site 9, site 12, site 13 and site 14 with adjusted p = 0.039, 0.009, 0.025, 0.046 and 0.027 respectively. However, the methylation level for the patients with small vessel subtype was not significant. We combined the methylation data from the above five sites for further sex-specific analysis. The results showed that the significant association only existed in women (adjusted p = 0.011, but not in men (adjusted p = 0.300.Female stroke cases have lower ERα methylation levels than those in the controls, especially in large-artery and cardio-embolic stroke subtypes. The study implies that women suffering from ischemic stroke of specific subtype may undergo different protective mechanisms to reduce the brain injury.

Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke.

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Orbe, J; Alexandru, N; Roncal, C; Belzunce, M; Bibiot, P; Rodriguez, J A; Meijers, J C M; Georgescu, A; Paramo, J A

2015-08-01

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fibrinolysis. Whereas TAFI deficiency may lead to a haemorrhagic tendency, data from TAFI knockout mice (TAFI-/-) are controversial and no differences have been reported in these animals after ischemic stroke. There are also no data regarding the role of circulating microparticles (MPs) in TAFI-/-. to examine the effect of tPA on the rate of intracranial haemorrhage (ICH) and on MPs generated in a model of ischemic stroke in TAFI-/- mice. Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10mg/Kg) on the infarct size and haemorrhage in the absence of TAFI. Immunofluorescence for Fluoro-Jade C was performed on frozen brain slides to analyse neuronal degeneration after ischemia. MPs were isolated from mouse blood and their concentrations calculated by flow cytometry. Compared with saline, tPA significantly increased the infarct size in TAFI-/- mice (p<0.05). Although plasma fibrinolytic activity (fibrin plate assay) was higher in these animals, no macroscopic or microscopic ICH was detected. A positive signal for apoptosis and degenerating neurons was observed in the infarct area, being significantly higher in tPA treated TAFI-/- mice (p<0.05). Interestingly, higher numbers of MPs were found in TAFI-/- plasma as compared to wild type, after stroke (p<0.05). TAFI deficiency results in increased brain damage in a model of thrombolysis after ischemic stroke, which was not associated with bleeding but with neuronal degeneration and MP production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes

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Kelly-Cobbs, Aisha I.; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H.; Ogbi, Safia N.; Fagan, Susan C.

2013-01-01

Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. PMID:23335797

Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis.

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Han-Jin Cui

Full Text Available Intracerebral hemorrhage (ICH is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition. Iron-mediated free radical injury is associated with secondary damage following ICH. Deferoxamine (DFX, a ferric-iron chelator, is a candidate drug for the treatment of ICH. We performed a systematic review of studies involving the administration of DFX following ICH. In total, 20 studies were identified that described the efficacy of DFX in animal models of ICH and assessed changes in the brain water content, neurobehavioral score, or both. DFX reduced the brain water content by 85.7% in animal models of ICH (-0.86, 95% CI: -.48- -0.23; P < 0.01; 23 comparisons, and improved the neurobehavioral score by -1.08 (95% CI: -1.23- -0.92; P < 0.01; 62 comparisons. DFX was most efficacious when administered 2-4 h after ICH at a dose of 10-50 mg/kg depending on species, and this beneficial effect remained for up to 24 h postinjury. The efficacy was higher with phenobarbital anesthesia, intramuscular injection, and lysed erythrocyte infusion, and in Fischer 344 rats or aged animals. Overall, although DFX was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality, and the limited number of studies conducting clinical trials.

PET measurement of FK506 concentration in a monkey model of stroke

International Nuclear Information System (INIS)

Murakami, Yoshihiro; Takamatsu, Hiroyuki; Noda, Akihiro; Osoda, Kazuhiko; Nishimura, Shintaro

2007-01-01

Introduction: The immunosuppressive agent FK506 (tacrolimus) has neuroprotective properties in an experimental model of cerebral ischemia. To improve the accuracy of clinical studies in acute stroke, a clinical dose setting should be based on the brain concentration, but not on the blood concentration of agents in humans. We have already established a measurement method using PET for FK506 concentration in the normal monkey brain, which could be applicable for human study; however, under ischemic conditions, in this study, we aimed to examine the brain concentration of FK506 in a monkey model of stroke. Methods: Studies were performed on six male cynomolgus monkeys (Macaca fascicularis) and a middle cerebral artery (MCA) occlusion model was used. Regional cerebral blood flow (rCBF) was measured by an intravenous injection of [ 15 O]H 2 O 165 min after MCA occlusion. FK506 (0.1 mg/kg) containing [ 11 C]FK506 was intravenously injected into the monkeys 180 min after MCA occlusion, and dynamic PET images were acquired for 30 min after administration. FK506 concentrations in the brain were calculated in moles per liter (M) units using the specific activity of injected FK506. Results: MCA occlusion produced ischemia, confirmed by rCBF measurement before the administration of [ 11 C]FK506. Fifteen minutes after FK506 (0.1 mg/kg) administration, the concentrations in the contralateral and ipsilateral cortex were 22.4±6.4 and 19.7±4.0 ng/g, respectively. Conclusion: We successfully measured the brain concentration of FK506 in a monkey model of stroke. The difference between the contralateral and ipsilateral concentrations of FK506 was not significant. This characteristic that FK506 readily penetrates ischemic tissue as well as normal tissue might explain the neuroprotective effect of FK506 in the ischemic brain and is suitable for the treatment of stroke patients

Modelling group dynamic animal movement

DEFF Research Database (Denmark)

Langrock, Roland; Hopcraft, J. Grant C.; Blackwell, Paul G.

2014-01-01

makes its movement decisions relative to the group centroid. The basic idea is framed within the flexible class of hidden Markov models, extending previous work on modelling animal movement by means of multi-state random walks. While in simulation experiments parameter estimators exhibit some bias......, to date, practical statistical methods which can include group dynamics in animal movement models have been lacking. We consider a flexible modelling framework that distinguishes a group-level model, describing the movement of the group's centre, and an individual-level model, such that each individual......Group dynamic movement is a fundamental aspect of many species' movements. The need to adequately model individuals' interactions with other group members has been recognised, particularly in order to differentiate the role of social forces in individual movement from environmental factors. However...

Stroke maximizing and high efficient hysteresis hybrid modeling for a rhombic piezoelectric actuator

Science.gov (United States)

Shao, Shubao; Xu, Minglong; Zhang, Shuwen; Xie, Shilin

2016-06-01

Rhombic piezoelectric actuator (RPA), which employs a rhombic mechanism to amplify the small stroke of PZT stack, has been widely used in many micro-positioning machineries due to its remarkable properties such as high displacement resolution and compact structure. In order to achieve large actuation range along with high accuracy, the stroke maximizing and compensation for the hysteresis are two concerns in the use of RPA. However, existing maximization methods based on theoretical model can hardly accurately predict the maximum stroke of RPA because of approximation errors that are caused by the simplifications that must be made in the analysis. Moreover, despite the high hysteresis modeling accuracy of Preisach model, its modeling procedure is trivial and time-consuming since a large set of experimental data is required to determine the model parameters. In our research, to improve the accuracy of theoretical model of RPA, the approximation theory is employed in which the approximation errors can be compensated by two dimensionless coefficients. To simplify the hysteresis modeling procedure, a hybrid modeling method is proposed in which the parameters of Preisach model can be identified from only a small set of experimental data by using the combination of discrete Preisach model (DPM) with particle swarm optimization (PSO) algorithm. The proposed novel hybrid modeling method can not only model the hysteresis with considerable accuracy but also significantly simplified the modeling procedure. Finally, the inversion of hysteresis is introduced to compensate for the hysteresis non-linearity of RPA, and consequently a pseudo-linear system can be obtained.

Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives.

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Pasupuleti, Mohan Kumar; Molahally, Subramanya Shetty; Salwaji, Supraja

2016-01-01

Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives

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Mohan Kumar Pasupuleti

2016-01-01

Full Text Available Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

Predicting recovery of cognitive function soon after stroke: differential modeling of logarithmic and linear regression.

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Suzuki, Makoto; Sugimura, Yuko; Yamada, Sumio; Omori, Yoshitsugu; Miyamoto, Masaaki; Yamamoto, Jun-ichi

2013-01-01

Cognitive disorders in the acute stage of stroke are common and are important independent predictors of adverse outcome in the long term. Despite the impact of cognitive disorders on both patients and their families, it is still difficult to predict the extent or duration of cognitive impairments. The objective of the present study was, therefore, to provide data on predicting the recovery of cognitive function soon after stroke by differential modeling with logarithmic and linear regression. This study included two rounds of data collection comprising 57 stroke patients enrolled in the first round for the purpose of identifying the time course of cognitive recovery in the early-phase group data, and 43 stroke patients in the second round for the purpose of ensuring that the correlation of the early-phase group data applied to the prediction of each individual's degree of cognitive recovery. In the first round, Mini-Mental State Examination (MMSE) scores were assessed 3 times during hospitalization, and the scores were regressed on the logarithm and linear of time. In the second round, calculations of MMSE scores were made for the first two scoring times after admission to tailor the structures of logarithmic and linear regression formulae to fit an individual's degree of functional recovery. The time course of early-phase recovery for cognitive functions resembled both logarithmic and linear functions. However, MMSE scores sampled at two baseline points based on logarithmic regression modeling could estimate prediction of cognitive recovery more accurately than could linear regression modeling (logarithmic modeling, R(2) = 0.676, PLogarithmic modeling based on MMSE scores could accurately predict the recovery of cognitive function soon after the occurrence of stroke. This logarithmic modeling with mathematical procedures is simple enough to be adopted in daily clinical practice.

Simulation Modeling and Optimization of Uniflow Scavenging System Parameters on Opposed-Piston Two-Stroke Engines

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Fukang Ma

2018-04-01

Full Text Available Based on the introduction of opposed-piston two-stroke (OP2S gasoline direct injection (GDI engines, the OP2S-GDI engine working principle and scavenging process were analyzed. GT-Power software was employed to model the working process based on the structural style and principle of OP2S-GDI engine. The tracer gas method and OP2S-GDI engine experiment were employed for model validation at full load of 6000 rpm. The OP2S-GDI engine scavenging system parameters were optimized, including intake port height stroke ratio, intake port circumference ratio, exhaust port height stroke ratio, exhaust port circumference ratio, and opposed-piston motion phase difference. At the same time, the effect of the port height stroke ratio and opposed-piston motion phase difference on effective compression ratio and expansion ratio were considered, and the indicated work was employed as the optimization objective. A three-level orthogonal experiment was applied in the calculation process to reduce the calculation work. The influence and correlation coefficient on the scavenging efficiency and delivery ratio were investigated by the orthogonal experiment analysis of intake and exhaust port height stroke ratio and circular utilization. The effect of the scavenging system parameters on delivery ratio, scavenging efficiency and indicated work were calculated to obtain the best parameters. The results show that intake port height stroke ratio is the main factor for the delivery ratio, while exhaust port height stroke ratio is the main factor to engine delivery ratio and scavenging efficiency.

Small Animal Models for Evaluating Filovirus Countermeasures.

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Banadyga, Logan; Wong, Gary; Qiu, Xiangguo

2018-05-11

The development of novel therapeutics and vaccines to treat or prevent disease caused by filoviruses, such as Ebola and Marburg viruses, depends on the availability of animal models that faithfully recapitulate clinical hallmarks of disease as it is observed in humans. In particular, small animal models (such as mice and guinea pigs) are historically and frequently used for the primary evaluation of antiviral countermeasures, prior to testing in nonhuman primates, which represent the gold-standard filovirus animal model. In the past several years, however, the filovirus field has witnessed the continued refinement of the mouse and guinea pig models of disease, as well as the introduction of the hamster and ferret models. We now have small animal models for most human-pathogenic filoviruses, many of which are susceptible to wild type virus and demonstrate key features of disease, including robust virus replication, coagulopathy, and immune system dysfunction. Although none of these small animal model systems perfectly recapitulates Ebola virus disease or Marburg virus disease on its own, collectively they offer a nearly complete set of tools in which to carry out the preclinical development of novel antiviral drugs.

Combination therapy of ifenprodil with piroxicam may be an effective therapeutic intervention in cerebral stroke: a hypothesis.

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Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana

2012-10-01

Owing to the intricate and multifaceted pathology of cerebral stroke, multiple drug therapy had long been suggested for effective stroke treatment. Therefore, the development of a potential new combination of drug is necessitated which can bring about desirable improved neuroprotection targeting different pathways against ischemic stroke. In this context, we hypothesize the combination effect of Piroxicam, a Non steroidal anti inflammatory drug with Ifenprodil, a NR2b selective NMDAR antagonist in animal model of cerebral ischemia. A few past studies have enumerated the neuroprotective roles of Piroxicam and Ifenprodil administered in singlet against cerebral ischemia in animal model, hence we hypothesized that by using Piroxicam and Ifenprodil in combination would provide additive neuroprotection than either of the agents used alone. In this article, we discuss our hypothesis regarding the possibility of Piroxicam and Ifenprodil as a potent combination which may have a positive therapeutic role in treatment of cerebral ischemia through its anti-inflammatory, anti-apoptotic and anti-oxidative characteristics of Piroxicam with Ifenprodil which has been proved to have neuroprotective, anticonvulsant and antinociceptive effects and has potentials for the treatment of several neuropsychiatric disorders, such as Parkinson's disease alcoholism and drug addiction. Copyright © 2012 Elsevier Ltd. All rights reserved.

Short-Lived Human Umbilical Cord-Blood-Derived Neural Stem Cells Influence the Endogenous Secretome and Increase the Number of Endogenous Neural Progenitors in a Rat Model of Lacunar Stroke.

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Jablonska, Anna; Drela, Katarzyna; Wojcik-Stanaszek, Luiza; Janowski, Miroslaw; Zalewska, Teresa; Lukomska, Barbara

2016-11-01

Stroke is the leading cause of severe disability, and lacunar stroke is related to cognitive decline and hemiparesis. There is no effective treatment for the majority of patients with stroke. Thus, stem cell-based regenerative medicine has drawn a growing body of attention due to the capabilities for trophic factor expression and neurogenesis enhancement. Moreover, it was shown in an experimental autoimmune encephalomyelitis (EAE) model that even short-lived stem cells can be therapeutic, and we have previously observed that phenomenon indirectly. Here, in a rat model of lacunar stroke, we investigated the molecular mechanisms underlying the positive therapeutic effects of short-lived human umbilical cord-blood-derived neural stem cells (HUCB-NSCs) through the distinct measurement of exogenous human and endogenous rat trophic factors. We have also evaluated neurogenesis and metalloproteinase activity as cellular components of therapeutic activity. As expected, we observed an increased proliferation and migration of progenitors, as well as metalloproteinase activity up to 14 days post transplantation. These changes were most prominent at the 7-day time point when we observed 30 % increases in the number of bromodeoxyuridine (BrdU)-positive cells in HUCB-NSC transplanted animals. The expression of human trophic factors was present until 7 days post transplantation, which correlated well with the survival of the human graft. For these 7 days, the level of messenger RNA (mRNA) in the analyzed trophic factors was from 300-fold for CNTF to 10,000-fold for IGF, much higher compared to constitutive expression in HUCB-NSCs in vitro. What is interesting is that there was no increase in the expression of rat trophic factors during the human graft survival, compared to that in non-transplanted animals. However, there was a prolongation of a period of increased trophic expression until 14 days post transplantation, while, in non-transplanted animals, there was a

Considerations for the optimization of induced white matter injury preclinical models

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Abdullah Shafique Ahmad

2015-08-01

Full Text Available The white matter injury in relation to acute neurologic conditions, especially stroke, has remained obscure until recently. Current advances in the imaging technologies in the field of stroke have confirmed that white matter injury plays an important role in the prognosis of stroke and suggest that white matter protection is essential for functional recovery and post-stroke rehabilitation. However, due to the lack of a reproducible animal model of white matter injury, the pathophysiology and mechanisms of this injury are not well studied. Moreover, producing selective white matter injury in animals, especially in rodents, has proven to be challenging. Problems associated with inducing selective white matter ischemic injury in the rodent derive from differences in the architecture of the brain, most particularly the ratio of white matter to gray matter in rodents compared to humans, the agents used to induce the injury, and the location of the injury. Aging, gender differences, and comorbidities further add to this complexity. This review provides a brief account of the techniques commonly used to induce general white matter injury in animal models (stroke and non-stroke related and highlights relevance, optimization issues, and translational potentials associated with this particular form of injury.

Aerodynamic efficiency of flapping flight: analysis of a two-stroke model.

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Wang, Z Jane

2008-01-01

To seek the simplest efficient flapping wing motions and understand their relation to steady flight, a two-stroke model in the quasi-steady limit was analyzed. It was found that a family of two-stroke flapping motions have aerodynamic efficiency close to, but slightly lower than, the optimal steady flight. These two-stroke motions share two common features: the downstroke is a gliding motion and the upstroke has an angle of attack close to the optimal of the steady flight of the same wing. With the reduced number of parameters, the aerodynamic cost function in the parameter space can be visualized. This was examined for wings of different lift and drag characteristics at Reynolds numbers between 10(2) and 10(6). The iso-surfaces of the cost function have a tube-like structure, implying that the solution is insensitive to a specific direction in the parameter space. Related questions in insect flight that motivated this work are discussed.

Social defeat models in animal science: What we have learned from rodent models.

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Toyoda, Atsushi

2017-07-01

Studies on stress and its impacts on animals are very important in many fields of science, including animal science, because various stresses influence animal production and animal welfare. In particular, the social stresses within animal groups have profound impact on animals, with the potential to induce abnormal behaviors and health problems. In humans, social stress induces several health problems, including psychiatric disorders. In animal stress models, social defeat models are well characterized and used in various research fields, particularly in studies concerning mental disorders. Recently, we have focused on behavior, nutrition and metabolism in rodent models of social defeat to elucidate how social stresses affect animals. In this review, recent significant progress in studies related to animal social defeat models are described. In the field of animal science, these stress models may contribute to advances in the development of functional foods and in the management of animal welfare. © 2017 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

Osteoarthritis: new insights in animal models.

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Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human 'idiopathic' OA, with late onset and slow progression, it is perhaps wise not to be overly enthusiastic about animal models that show severe chondrodysplasia and very early OA. Advantage by using genetically engineered mouse models, in comparison with other surgically induced models, is that molecular etiology is known. Find potential molecular markers for the onset of the disease and pay attention to the role of gender and environmental factors should be very helpful in the study of mice that acquire premature OA. Surgically induced destabilization of joint is the most widely used induction method. These models allow the temporal control of disease induction and follow predictable progression of the disease. In animals, ACL transection and meniscectomy show a speed of onset and severity of disease higher than in humans after same injury.

Modeling the Cost Effectiveness of Neuroimaging-Based Treatment of Acute Wake-Up Stroke.

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Ankur Pandya

Full Text Available Thrombolytic treatment (tissue-type plasminogen activator [tPA] is only recommended for acute ischemic stroke patients with stroke onset time 4.5 hours, 46.3% experienced a good stroke outcome. Lifetime discounted QALYs and costs were 5.312 and $88,247 for the no treatment strategy and 5.342 and $90,869 for the MRI-based strategy, resulting in an ICER of $88,000/QALY. Results were sensitive to variations in patient- and provider-specific factors such as sleep duration, hospital travel and door-to-needle times, as well as onset probability distribution, MRI specificity, and mRS utility values.Our model-based findings suggest that an MRI-based treatment strategy for this population could be cost-effective and quantifies the impact that patient- and provider-specific factors, such as sleep duration, hospital travel and door-to-needle times, could have on the optimal decision for wake-up stroke patients.

Animal models of osteoporosis - necessity and limitations

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Turner A. Simon

2001-06-01

Full Text Available There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep are a promising model for various reasons: they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and the sheep's bones are large enough to evaluate orthopaedic implants. Most animal models have used females and osteoporosis in the male has been largely ignored. Recently, interest in development of appropriate prosthetic devices which would stimulate osseointegration into osteoporotic, appendicular, axial and mandibular bone has intensified. Augmentation of osteopenic lumbar vertebrae with bioactive ceramics (vertebroplasty is another area that will require testing in the appropriate animal model. Using experimental animal models for the study of these different facets of osteoporosis minimizes some of the difficulties associated with studying the disease in humans, namely time and behavioral variability among test subjects. New experimental drug therapies and orthopaedic implants can potentially be tested on large numbers of animals subjected to a level of experimental control impossible in human clinical research.

Animal models for microbicide safety and efficacy testing.

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Veazey, Ronald S

2013-07-01

Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

Human neural stem cells over-expressing VEGF provide neuroprotection, angiogenesis and functional recovery in mouse stroke model.

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Hong J Lee

Full Text Available 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.

Four-Stroke, Internal Combustion Engine Performance Modeling

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Wagner, Richard C.

In this thesis, two models of four-stroke, internal combustion engines are created and compared. The first model predicts the intake and exhaust processes using isentropic flow equations augmented by discharge coefficients. The second model predicts the intake and exhaust processes using a compressible, time-accurate, Quasi-One-Dimensional (Q1D) approach. Both models employ the same heat release and reduced-order modeling of the cylinder charge. Both include friction and cylinder loss models so that the predicted performance values can be compared to measurements. The results indicate that the isentropic-based model neglects important fluid mechanics and returns inaccurate results. The Q1D flow model, combined with the reduced-order model of the cylinder charge, is able to capture the dominant intake and exhaust fluid mechanics and produces results that compare well with measurement. Fluid friction, convective heat transfer, piston ring and skirt friction and temperature-varying specific heats in the working fluids are all shown to be significant factors in engine performance predictions. Charge blowby is shown to play a lesser role.

Proper housing conditions in experimental stroke studies – special emphasis on environmental enrichment

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Satu eMering

2015-03-01

Full Text Available Environmental enrichment provides laboratory animals with novelty and extra space, allowing different forms of multisensory stimulation ranging from social grouping to enhanced motor activity. At the extreme end of the spectrum, one can have a super-enriched environment. Environmental enrichment is believed to result in improved cognitive and sensorimotor functions both in naïve rodents and in animals with brain lesions such as those occurring after a stroke. Robust behavioral effects in animals which have suffered a stroke are probably related not only to neuronal plasticity in the perilesional cortex but also in remote brain areas. There is emerging evidence to suggest that testing restorative therapies in an enriched environment can maximize treatment effects, e.g., the perilesional milieu seems to be more receptive to concomitant pharmacotherapy and/or cell therapy. This review provides an updated overview on the effect of an enriched environment in stroke animals from the practical points to be considered when planning experiments to the mechanisms explaining why combined therapies can contribute to behavioral improvement in a synergistic manner.

Animal Models of Chemotherapy-induced Mucositis

DEFF Research Database (Denmark)

Sangild, Per T; Shen, René Liang; Pontoppidan, Peter Erik Lotko

2018-01-01

constitution). Here, we briefly describe CIM pathophysiology, particularly the basic knowledge that has been obtained from CIM animal models. These model studies have indicated potential new preventive and ameliorating interventions, including supplementation with natural bioactive diets (e.g. milk fractions...... easier make clinically-relevant treatment regimens possible. In synergy, animal models improve the basic pathophysiological understanding of CIM and provide new ideas for treatment that are required to make competent decisions in clinical practice....

Stroke after coronary artery bypass grafting. Is there place for a stroke-risk stratification model?

NARCIS (Netherlands)

Noyez, L.; Swieten, H.A. van

2009-01-01

AIM: Preoperative carotid screening is common in the prevention of perioperative stroke. The authors describe our experience with selective screening of patients with a recent (<1 year) neurological event. Because many variables are related with the development of perioperative stroke we

Therapeutic Effect of Ligustilide-Stimulated Adipose-Derived Stem Cells in a Mouse Thromboembolic Stroke Model.

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Chi, Kang; Fu, Ru-Huei; Huang, Yu-Chuen; Chen, Shih-Yin; Lin, Shinn-Zong; Huang, Pi-Chun; Lin, Po-Cheng; Chang, Fu-Kuei; Liu, Shih-Ping

2016-01-01

Stroke is a result of cerebral ischemia that triggers a cascade of both physiological and biochemical events. No effective treatment is available for stroke; however, stem cells have the potential to rescue tissue from the effects of stroke. Adipose-derived stem cells (ADSCs) are an abundant source of adult stem cells; therefore, ADSC therapy can be considered as a future strategy for regenerative medicine. However, more research is required to improve the effectiveness of transplanted ADSCs as a treatment for stroke in the mouse stroke model. Ligustilide, isolated from the herb Angelica sinensis, exhibits a protective effect on neurons and inhibits inflammation. We also demonstrated that ligustilide treatment increases the expression levels of homing factors such as SDF-1 and CXCR4. In the present study, we evaluated the therapeutic effects of ADSC transplantation and ligustilide treatment in a mouse thromboembolic stroke model by behavioral tests, including beam walking, locomotor activity, and rotarod analysis. ADSCs pretreated with ligustilide were transplanted into the brains of stroke mice. The results showed that the therapeutic effect of ADSCs pretreated with ligustilide was better than that of ADSCs without ligustilide pretreatment. There was no difference between the recovery of mice treated by ADSC transplantation combined with subcutaneous ligustilide injection and that of mice treated only with ADSCs. The TUNEL assay showed fewer apoptotic cells in the brains of mice transplanted with ADSCs pretreated with ligustilide as well as in those without pretreatment. In summary, pretreatment of ADSCs with ligustilide improves the therapeutic efficacy of ADSC transplantation. The results of this study will help improve stem cell therapies being developed for future clinical applications.

Animal models for dengue vaccine development and testing.

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Na, Woonsung; Yeom, Minjoo; Choi, Il-Kyu; Yook, Heejun; Song, Daesub

2017-07-01

Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.

Bounds on the Cabibbo-Kobayashi-Maskawa matrix elements vertical strokeVtdvertical stroke and vertical strokeVtsvertical stroke from experiments on B0-anti B0 mixings

International Nuclear Information System (INIS)

Ali, A.; Eijk, B. van; Have, I. ten

1987-01-01

We present a theoretical analysis of the process panti p → μ ± μ ± X, μ ± X', μ + μ - X' due to heavy flavour production and decays, based on perturbative quantum chromodynamics, QCD. We find reasonable agreement for the inclusive rates and distributions between the UA1 measurement and our calculations, with the exception of the dimuon ratio R(±±/+--), which is found typically a factor ≅ 1.8 smaller than the UA1 data. We interpret this excess in terms of B s 0 -anti B s 0 mixing and obtain a lower bound on the mixing probability, ρ s > 0.14. In the standard model this implies a lower bound on the Cabibbo-Kobayashi-Maskawa matrix element vertical strokeV ts vertical stroke given the top quark mass. The lower bound on vertical strokeV ts vertical stroke and the upper bound on vertical strokeV td vertical stroke, obtained from the (upper bound) B d 0 -anti B d 0 mixing probability, ρ d , from e + e - experiments are worked out. (orig.)

Comparison of Multi-Tensor Diffusion Models' Performance for White Matter Integrity Estimation in Chronic Stroke

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Olena G. Filatova

2018-04-01

Full Text Available Better insight into white matter (WM alterations after stroke onset could help to understand the underlying recovery mechanisms and improve future interventions. MR diffusion imaging enables to assess such changes. Our goal was to investigate the relation of WM diffusion characteristics derived from diffusion models of increasing complexity with the motor function of the upper limb. Moreover, we aimed to evaluate the variation of such characteristics across different WM structures of chronic stroke patients in comparison to healthy subjects. Subjects were scanned with a two b-value diffusion-weighted MRI protocol to exploit multiple diffusion models: single tensor, single tensor with isotropic compartment, bi-tensor model, bi-tensor with isotropic compartment. From each model we derived the mean tract fractional anisotropy (FA, mean (MD, radial (RD and axial (AD diffusivities outside the lesion site based on a WM tracts atlas. Asymmetry of these measures was correlated with the Fugl-Meyer upper extremity assessment (FMA score and compared between patient and control groups. Eighteen chronic stroke patients and eight age-matched healthy individuals participated in the study. Significant correlation of the outcome measures with the clinical scores of stroke recovery was found. The lowest correlation of the corticospinal tract FAasymmetry and FMA was with the single tensor model (r = −0.3, p = 0.2 whereas the other models reported results in the range of r = −0.79 ÷ −0.81 and p = 4E-5 ÷ 8E-5. The corticospinal tract and superior longitudinal fasciculus showed most alterations in our patient group relative to controls. Multiple compartment models yielded superior correlation of the diffusion measures and FMA compared to the single tensor model.

Animal models of pancreatic cancer for drug research.

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Kapischke, Matthias; Pries, Alexandra

2008-10-01

The operative and conservative results of therapy in pancreatic ductal adenocarcinoma remain appallingly poor. This underlines the demand for further research for effective anticancer drugs. The various animal models remain the essential method for the determination of efficacy of substances during preclinical phase. Unfortunately, most of these tested substances showed a good efficacy in pancreatic carcinoma in the animal model but were not confirmed during the clinical phase. The available literature in PubMed, Medline, Ovid and secondary literature was searched regarding the available animal models for drug testing against pancreatic cancer. The models were analyzed regarding their pros and cons in anticancer drug testing. The different modifications of the orthotopic model (especially in mice) seem at present to be the best model for anticancer testing in pancreatic carcinoma. The value of genetically engineered animal model (GEM) and syngeneic models is on debate. A good selection of the model concerning the questions supposed to be clarified may improve the comparability of the results of animal experiments compared to clinical trials.

Animal models of cardiac cachexia.

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Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

2016-09-15

Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Latest animal models for anti-HIV drug discovery.

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Sliva, Katja

2015-02-01

HIV research is limited by the fact that lentiviruses are highly species specific. The need for appropriate models to promote research has led to the development of many elaborate surrogate animal models. This review looks at the history of animal models for HIV research. Although natural animal lentivirus infections and chimeric viruses such as chimera between HIV and simian immunodeficiency virus and simian-tropic HIV are briefly discussed, the main focus is on small animal models, including the complex design of the 'humanized' mouse. The review also traces the historic evolution and milestones as well as depicting current models and future prospects for HIV research. HIV research is a complex and challenging task that is highly manpower-, money- and time-consuming. Besides factors such as hypervariability and latency, the lack of appropriate animal models that exhibit and recapitulate the entire infectious process of HIV, is one of the reasons behind the failure to eliminate the lentivirus from the human population. This obstacle has led to the exploitation and further development of many sophisticated surrogate animal models for HIV research. While there is no animal model that perfectly mirrors and mimics HIV infections in humans, there are a variety of host species and viruses that complement each other. Combining the insights from each model, and critically comparing the results obtained with data from human clinical trials should help expand our understanding of HIV pathogenesis and drive future drug development.

Animal models for auditory streaming

Science.gov (United States)

Itatani, Naoya

2017-01-01

Sounds in the natural environment need to be assigned to acoustic sources to evaluate complex auditory scenes. Separating sources will affect the analysis of auditory features of sounds. As the benefits of assigning sounds to specific sources accrue to all species communicating acoustically, the ability for auditory scene analysis is widespread among different animals. Animal studies allow for a deeper insight into the neuronal mechanisms underlying auditory scene analysis. Here, we will review the paradigms applied in the study of auditory scene analysis and streaming of sequential sounds in animal models. We will compare the psychophysical results from the animal studies to the evidence obtained in human psychophysics of auditory streaming, i.e. in a task commonly used for measuring the capability for auditory scene analysis. Furthermore, the neuronal correlates of auditory streaming will be reviewed in different animal models and the observations of the neurons’ response measures will be related to perception. The across-species comparison will reveal whether similar demands in the analysis of acoustic scenes have resulted in similar perceptual and neuronal processing mechanisms in the wide range of species being capable of auditory scene analysis. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044022

5-year survival and rehospitalization due to stroke recurrence among patients with hemorrhagic or ischemic strokes in Singapore.

Science.gov (United States)

Sun, Yan; Lee, Sze Haur; Heng, Bee Hoon; Chin, Vivien S

2013-10-03

Stroke is the 4th leading cause of death and 1st leading cause of disability in Singapore. However the information on long-term post stroke outcomes for Singaporean patients was limited. This study aimed to investigate the post stroke outcomes of 5-year survival and rehospitalization due to stroke recurrence for hemorrhagic and ischemic stroke patients in Singapore. The outcomes were stratified by age, ethnic group, gender and stroke types. The causes of death and stroke recurrence were also explored in the study. A multi-site retrospective cohort study. Patients admitted for stroke at any of the three hospitals in the National Healthcare Group of Singapore were included in the study. All study patients were followed up to 5 years. Kaplan-Meier was applied to study the time to first event, death or rehospitalization due to stroke recurrence. Cox proportional hazard model was applied to study the time to death with adjustment for stroke type, age, sex, ethnic group, and admission year. Cumulative incidence model with competing risk was applied for comparing the risks of rehospitalization due to stroke recurrence with death as the competing risk. Totally 12,559 stroke patients were included in the study. Among them, 59.3% survived for 5 years; 18.4% were rehospitalized due to stroke recurrence in 5 years. The risk of stroke recurrence and mortality increased with age in all stroke types. Gender, ethnic group and admitting year were not significantly associated with the risk of mortality or stroke recurrence in hemorrhagic stroke. Male or Malay patient had higher risk of stroke recurrence and mortality in ischemic stroke. Hemorrhagic stroke had higher early mortality while ischemic stroke had higher recurrence and late mortality. The top cause of death among died stroke patients was cerebrovascular diseases, followed by pneumonia and ischemic heart diseases. The recurrent stroke was most likely to be the same type as the initial stroke among rehospitalized stroke

The necessity of animal models in pain research.

Science.gov (United States)

Mogil, Jeffrey S; Davis, Karen D; Derbyshire, Stuart W

2010-10-01

There exists currently a fair degree of introspection in the pain research community about the value of animal research. This review represents a defense of animal research in pain. We discuss the inherent advantage of animal models over human research as well as the crucial complementary roles animal studies play vis-à-vis human imaging and genetic studies. Finally, we discuss recent developments in animal models of pain that should improve the relevance and translatability of findings using laboratory animals. We believe that pain research using animal models is a continuing necessity-to understand fundamental mechanisms, identify new analgesic targets, and inform, guide and follow up human studies-if novel analgesics are to be developed for the treatment of chronic pain. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Animal models of papillomavirus pathogenesis.

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Campo, M Saveria

2002-11-01

Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less

Animal models of preeclampsia; uses and limitations.

LENUS (Irish Health Repository)

McCarthy, F P

2012-01-31

Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality and has an unknown etiology. The limited progress made regarding new treatments to reduce the incidence and severity of preeclampsia has been attributed to the difficulties faced in the development of suitable animal models for the mechanistic research of this disease. In addition, animal models need hypotheses on which to be based and the slow development of testable hypotheses has also contributed to this poor progress. The past decade has seen significant advances in our understanding of preeclampsia and the development of viable reproducible animal models has contributed significantly to these advances. Although many of these models have features of preeclampsia, they are still poor overall models of the human disease and limited due to lack of reproducibility and because they do not include the complete spectrum of pathophysiological changes associated with preeclampsia. This review aims to provide a succinct and comprehensive assessment of current animal models of preeclampsia, their uses and limitations with particular attention paid to the best validated and most comprehensive models, in addition to those models which have been utilized to investigate potential therapeutic interventions for the treatment or prevention of preeclampsia.

Frequencies of circulating B- and T-lymphocytes as indicators for stroke outcomes

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Wang Y

2017-10-01

Full Text Available Yanling Wang,1 Jihong Liu,1 Xuemei Wang,1 Zongjian Liu,2 Fengwu Li,1 Fenghua Chen,3 Xiaokun Geng,1 Zhili Ji,2 Huishan Du,1 Xiaoming Hu1,3 1Department of Neurology, China-America Institute of Neuroscience, 2Central Laboratory, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Neurology, Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Background: Stroke has high mortality and morbidity. Biomarkers are required for to predict stroke outcomes, which could help clinicians to provide rationale approaches for patient management. The dynamic changes in circulating immune cells have been reported in stroke patients and animal models of stroke.Aim: The aim of this study was to explore biomarkers to predict stroke outcomes by investigating the relationship between the frequencies of circulating immune cells and stroke outcomes.Methods: In all, 50 acute ischemic stroke (AIS patients were enrolled. Their blood samples were collected upon hospital admission and on day 1 and day 7 after stroke, and the leukocyte subsets were analyzed by flow cytometry. The dynamic changes in some types of immune cells in the AIS course and their correlation with clinical parameters were analyzed. Blood samples from 123 age- and gender-matched healthy subjects were used as controls.Results: The proportions of T-lymphocytes and NK cells in stroke patients were significantly lower than in healthy controls. The frequencies of B- and T-lymphocytes were negatively correlated with stroke severity at onset, including neurological deficits as assessed by National Institutes of Health Stroke Scale (NIHSS, and infarct volume as measured by the diffusion-weighted images (DWIs of magnetic resonance (MR. Logistic regression analysis showed that modified Rankin scale (mRs scores, a score system for the long-term neurological dysfunctions, were negatively correlated

Gradually Increased Training Intensity Benefits Rehabilitation Outcome after Stroke by BDNF Upregulation and Stress Suppression

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Jing Sun

2014-01-01

Full Text Available Physical training is necessary for effective rehabilitation in the early poststroke period. Animal studies commonly use fixed training intensity throughout rehabilitation and without adapting it to the animals' recovered motor ability. This study investigated the correlation between training intensity and rehabilitation efficacy by using a focal ischemic stroke rat model. Eighty male Sprague-Dawley rats were induced with middle cerebral artery occlusion/reperfusion surgery. Sixty rats with successful stroke were then randomly assigned into four groups: control (CG, n=15, low intensity (LG, n=15, gradually increased intensity (GIG, n=15, and high intensity (HG, n=15. Behavioral tests were conducted daily to evaluate motor function recovery. Stress level and neural recovery were evaluated via plasma corticosterone and brain-derived neurotrophic factor (BDNF concentration, respectively. GIG rats significantly (P<0.05 recovered motor function and produced higher hippocampal BDNF (112.87 ± 25.18 ng/g. GIG and LG rats exhibited similar stress levels (540.63 ± 117.40 nM/L and 508.07 ± 161.30 nM/L, resp., which were significantly lower (P<0.05 than that (716.90 ± 156.48 nM/L of HG rats. Training with gradually increased intensity achieved better recovery with lower stress. Our observations indicate that a training protocol that includes gradually increasing training intensity should be considered in both animal and clinical studies for better stroke recovery.

Animation of 3D Model of Human Head

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V. Michalcin

2007-04-01

Full Text Available The paper deals with the new algorithm of animation of 3D model of the human head in combination with its global motion. The designed algorithm is very fast and with low calculation requirements, because it does not need the synthesis of the input videosequence for estimation of the animation parameters as well as the parameters of global motion. The used 3D model Candide generates different expressions using its animation units which are controlled by the animation parameters. These ones are estimated on the basis of optical flow without the need of extracting of the feature points in the frames of the input videosequence because they are given by the selected vertices of the animation units of the calibrated 3D model Candide. The established multiple iterations inside the designed animation algorithm of 3D model of the human head between two successive frames significantly improved its accuracy above all for the large motion.

Animation Augmented Reality Book Model (AAR Book Model) to Enhance Teamwork

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Chujitarom, Wannaporn; Piriyasurawong, Pallop

2017-01-01

This study aims to synthesize an Animation Augmented Reality Book Model (AAR Book Model) to enhance teamwork and to assess the AAR Book Model to enhance teamwork. Samples are five specialists that consist of one animation specialist, two communication and information technology specialists, and two teaching model design specialists, selected by…

Theophylline as an add-on to thrombolytic therapy in acute ischaemic stroke (TEA-Stroke)

DEFF Research Database (Denmark)

Modrau, Boris; Hjort, Niels; Østergaard, Leif

2016-01-01

the collateral supply in acute ischaemic brain tissue and thus facilitate reperfusion despite proximal vessel occlusion. The primary study objective is to evaluate whether theophylline is safe and efficient in acute ischaemic stroke patients as an add-on to thrombolytic therapy.MethodsThe TEA-Stroke Trial...... models, clinical case series and randomized clinical trials are controversial. A Cochrane analysis from 2004 concluded that there was not enough evidence to assess whether theophylline is safe and improves outcomes in patients with acute ischaemic stroke. The TEA-Stroke Trial will clarify whether...

Animal models of cerebral arterial gas embolism

NARCIS (Netherlands)

Weenink, Robert P.; Hollmann, Markus W.; van Hulst, Robert A.

2012-01-01

Cerebral arterial gas embolism is a dreaded complication of diving and invasive medical procedures. Many different animal models have been used in research on cerebral arterial gas embolism. This review provides an overview of the most important characteristics of these animal models. The properties

Stem Cell-Based Therapies for Ischemic Stroke

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Lei Hao

2014-01-01

Full Text Available In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs, inducible pluripotent stem cells (iPSCs, neural stem cells (NSCs, and mesenchymal stem cell (MSCs might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future.

Quantifying Selection Bias in National Institute of Health Stroke Scale Data Documented in an Acute Stroke Registry.

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Thompson, Michael P; Luo, Zhehui; Gardiner, Joseph; Burke, James F; Nickles, Adrienne; Reeves, Mathew J

2016-05-01

As a measure of stroke severity, the National Institutes of Health Stroke Scale (NIHSS) is an important predictor of patient- and hospital-level outcomes, yet is often undocumented. The purpose of this study is to quantify and correct for potential selection bias in observed NIHSS data. Data were obtained from the Michigan Stroke Registry and included 10 262 patients with ischemic stroke aged ≥65 years discharged from 23 hospitals from 2009 to 2012, of which 74.6% of patients had documented NIHSS. We estimated models predicting NIHSS documentation and NIHSS score and used the Heckman selection model to estimate a correlation coefficient (ρ) between the 2 model error terms, which quantifies the degree of selection bias in the documentation of NIHSS. The Heckman model found modest, but significant, selection bias (ρ=0.19; 95% confidence interval: 0.09, 0.29; P2 points, which could significantly alter the risk profile of hospitals treating patients with ischemic stroke and subsequent hospital risk-adjusted outcomes. © 2016 American Heart Association, Inc.

Towards a reliable animal model of migraine

DEFF Research Database (Denmark)

Olesen, Jes; Jansen-Olesen, Inger

2012-01-01

The pharmaceutical industry shows a decreasing interest in the development of drugs for migraine. One of the reasons for this could be the lack of reliable animal models for studying the effect of acute and prophylactic migraine drugs. The infusion of glyceryl trinitrate (GTN) is the best validated...... and most studied human migraine model. Several attempts have been made to transfer this model to animals. The different variants of this model are discussed as well as other recent models....

Dietary patterns are associated with incident stroke and contribute to excess risk of stroke in Black Americans

Science.gov (United States)

Judd, Suzanne E; Gutiérrez, Orlando M.; Newby, PK; Howard, George; Howard, Virginia J; Locher, Julie L; Kissela, Brett M; Shikany, James M

2014-01-01

Background and Purpose Black Americans and residents of the Southeastern United States, are at increased risk of stroke. Diet is one of many potential factors proposed that might explain these racial and regional disparities. Methods Between 2003–2007, the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study enrolled 30,239 black and white Americans aged 45 years or older. Dietary patterns were derived using factor analysis and foods from food frequency data. Incident strokes were adjudicated using medical records by a team of physicians. Cox proportional hazards models were used to examine risk of stroke. Results Over 5.7 years, 490 incident strokes were observed. In a multivariable-adjusted analysis, greater adherence to the Plant-based pattern was associated with lower stroke risk (HR=0.71; 95% CI=0.56–0.91; ptrend=0.005). This association was attenuated after addition of income, education, total energy intake, smoking, and sedentary behavior. Participants with a higher adherence to the Southern pattern experienced a 39% increased risk of stroke (HR=1.39; 95% CI=1.05, 1.84), with a significant (p = 0.009) trend across quartiles. Including Southern pattern in the model mediated the black-white risk of stroke by 63%. Conclusions These data suggest that adherence to a Southern style diet may increase the risk of stroke while adherence to a more plant-based diet may reduce stroke risk. Given the consistency of finding a dietary impact on stroke risk across studies, discussing nutrition patterns during risk screening may be an important step in reducing stroke. PMID:24159061

Advances in Animal Models of Hepatitis B Virus Infection

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Zhang Hang

2015-12-01

Full Text Available Hepatitis B virus (HBV infection seriously affects human health. Stable and reliable animal models of HBV infection bear significance in studying pathogenesis of this health condition and development of intervention measures. HBV exhibits high specificity for hosts, and chimpanzee is long used as sole animal model of HBV infection. However, use of chimpanzees is strictly constrained because of ethical reasons. Many methods were used to establish small-animal models of HBV infection. Tupaia is the only nonprimate animal that can be infected by HBV. Use of HBV-related duck hepatitis virus and marmot hepatitis virus infection model contributed to evaluation of mechanism of HBV replication and HBV treatment methods. In recent years, development of human–mouse chimeric model provided possibility of using common experimental animals to carry out HBV research. These models feature their own advantages and disadvantages and can be complementary in some ways. This study provides an overview of current and commonly used animal models of HBV infection.

CITICOLIN IN THE TREATMENT OF STROKE AND VASCULAR COGNITIVE DISORDERS

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Vladimir Anatol'evich Parfenov

2009-01-01

Full Text Available Citicolin (ceraxon is used as a neuroprotector in the treatment of acute stroke and vascular cognitive disorders. Experimental animal studies have demonstrated that citicolin reduces the extent of cerebral infarct and increases the degree of functional recovery. A few clinical trials have provided evidence for the efficacy of intravenous or oral citicolin used within the first 24 hours of ischemic stroke or cerebral hemorrhage in recovery of neurological functions. Citicolin is effective in memory and behavioral disorders in elderly patients with chronic cerebrovascular diseases. The use of citicolin has been found to be safe in stroke and vascular cognitive disorders

Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis.

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Mei-Xue Dong

Full Text Available Recombinant tissue plasminogen activator (rtPA is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA on cerebral infarction besides its thrombolysis property in mechanical animal stroke.Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger's test were obtained to detect publication bias.We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate.This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA.

Web-based tool for dynamic functional outcome after acute ischemic stroke and comparison with existing models.

Science.gov (United States)

Ji, Ruijun; Du, Wanliang; Shen, Haipeng; Pan, Yuesong; Wang, Penglian; Liu, Gaifen; Wang, Yilong; Li, Hao; Zhao, Xingquan; Wang, Yongjun

2014-11-25

Acute ischemic stroke (AIS) is one of the leading causes of death and adult disability worldwide. In the present study, we aimed to develop a web-based risk model for predicting dynamic functional status at discharge, 3-month, 6-month, and 1-year after acute ischemic stroke (Dynamic Functional Status after Acute Ischemic Stroke, DFS-AIS). The DFS-AIS was developed based on the China National Stroke Registry (CNSR), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Good functional outcome was defined as modified Rankin Scale (mRS) score ≤ 2 at discharge, 3-month, 6-month, and 1-year after AIS, respectively. Independent predictors of each outcome measure were obtained using multivariable logistic regression. The area under the receiver operating characteristic curve (AUROC) and plot of observed and predicted risk were used to assess model discrimination and calibration. A total of 12,026 patients were included and the median age was 67 (interquartile range: 57-75). The proportion of patients with good functional outcome at discharge, 3-month, 6-month, and 1-year after AIS was 67.9%, 66.5%, 66.9% and 66.9%, respectively. Age, gender, medical history of diabetes mellitus, stroke or transient ischemic attack, current smoking and atrial fibrillation, pre-stroke dependence, pre-stroke statins using, admission National Institutes of Health Stroke Scale score, admission blood glucose were identified as independent predictors of functional outcome at different time points after AIS. The DFS-AIS was developed from sets of predictors of mRS ≤ 2 at different time points following AIS. The DFS-AIS demonstrated good discrimination in the derivation and validation cohorts (AUROC range: 0.837-0.845). Plots of observed versus predicted likelihood showed excellent calibration in the derivation and validation cohorts (all r = 0.99, P discrimination for good functional outcome and mortality at discharge, 3-month, 6

Large animal models for vaccine development and testing.

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Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A

2015-01-01

The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Hip Hop Stroke: Study Protocol for a Randomized Controlled Trial to Address Stroke Literacy.

Science.gov (United States)

Williams, Olajide; Leighton-Herrmann, Ellyn; DeSorbo, Alexandra; Hecht, Mindy; Hedmann, Monique; Huq, Saima; Gerin, William; Chinchilli, Vernon; Ogedegbe, Gbenga; Noble, James

2015-10-01

Stroke is the fifth leading cause of death and the leading cause of serious long-term adult disability in the US. Acute stroke treatments with intravenous thrombolysis and endovascular therapy are proven to reduce disability, however a critical limitation on their effectiveness is the narrow time window for administration, which is 4.5 hours and 6 hours respectively from the onset of symptoms. Our overarching goal is to reduce pre-hospital delays to acute stroke treatments in economically disadvantaged minority communities where the greatest delays exist, using Hip Hop Stroke. Hip Hop Stroke (HHS) is a school-based, child-mediated, culturally-tailored stroke communication multimedia intervention developed using validated models of behavior change and designed to improve stroke literacy (knowledge of stroke symptoms, the urgent need to call 911, and prevention measures) of 4 th , 5 th and 6 th grade students and their parents residing in poor urban communities. Children in the intervention arm will receive the HHS intervention, while those in the attentional control arm will receive standardized nutrition education based on the USDA's MyPyramid program. Children will be trained and motivated to share stroke information with their parents or other adult caregiver. Both children and parents will complete a stroke knowledge assessment at baseline, immediately following the program, and at 3-months post-program. The primary outcome is the effect of the child mediation on parental stroke literacy. Stroke literate children, a captive audience in school systems, may represent a viable channel for spreading stroke information into households of poor urban communities where mass media stroke campaigns have shown the lowest penetration. These children may also call 911 when witnessing a stroke in their homes or communities. The HHS program may highlight the potential role of children in the chain of stroke recovery as a strategy for reducing prehospital delays to acute stroke

Elements of episodic-like memory in animal models.

Science.gov (United States)

Crystal, Jonathon D

2009-03-01

Representations of unique events from one's past constitute the content of episodic memories. A number of studies with non-human animals have revealed that animals remember specific episodes from their past (referred to as episodic-like memory). The development of animal models of memory holds enormous potential for gaining insight into the biological bases of human memory. Specifically, given the extensive knowledge of the rodent brain, the development of rodent models of episodic memory would open new opportunities to explore the neuroanatomical, neurochemical, neurophysiological, and molecular mechanisms of memory. Development of such animal models holds enormous potential for studying functional changes in episodic memory in animal models of Alzheimer's disease, amnesia, and other human memory pathologies. This article reviews several approaches that have been used to assess episodic-like memory in animals. The approaches reviewed include the discrimination of what, where, and when in a radial arm maze, dissociation of recollection and familiarity, object recognition, binding, unexpected questions, and anticipation of a reproductive state. The diversity of approaches may promote the development of converging lines of evidence on the difficult problem of assessing episodic-like memory in animals.

Prediction of Major Vascular Events after Stroke

DEFF Research Database (Denmark)

Ovbiagele, Bruce; Goldstein, Larry B.; Amarenco, Pierre

2014-01-01

BACKGROUND: Identifying patients with recent stroke or transient ischemic attack (TIA) at high risk of major vascular events (MVEs; stroke, myocardial infarction, or vascular death) may help optimize the intensity of secondary preventive interventions. We evaluated the relationships between...... the baseline Framingham Coronary Risk Score (FCRS) and a novel risk prediction model and with the occurrence of MVEs after stroke or TIA in subjects enrolled in the Stroke Prevention by Aggressive Reduction in Cholesterol Level (SPARCL) trial. METHODS: Data from the 4731 subjects enrolled in the SPARCL study...... were analyzed. Hazard ratios (HRs) from Cox regression models were used to determine the risk of subsequent MVEs based on the FCRS predicting 20% or more 10-year coronary heart disease risk. The novel risk model was derived based on multivariable modeling with backward selection. Model discrimination...

Chimeric animal models in human stem cell biology.

Science.gov (United States)

Glover, Joel C; Boulland, Jean-Luc; Halasi, Gabor; Kasumacic, Nedim

2009-01-01

The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the chicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

National Trends in Patients Hospitalized for Stroke and Stroke Mortality in France, 2008 to 2014.

Science.gov (United States)

Lecoffre, Camille; de Peretti, Christine; Gabet, Amélie; Grimaud, Olivier; Woimant, France; Giroud, Maurice; Béjot, Yannick; Olié, Valérie

2017-11-01

Stroke is the leading cause of death in women and the third leading cause in men in France. In young adults (ie, stroke was observed at a local scale between 1985 and 2011. After the implementation of the 2010 to 2014 National Stroke Action Plan, this study investigates national trends in patients hospitalized by stroke subtypes, in-hospital mortality, and stroke mortality between 2008 and 2014. Hospitalization data were extracted from the French national hospital discharge databases and mortality data from the French national medical causes of death database. Time trends were tested using a Poisson regression model. From 2008 to 2014, the age-standardized rates of patients hospitalized for ischemic stroke increased by 14.3% in patients hemorrhagic stroke was stable (+2.0%), irrespective of age and sex. The proportion of patients hospitalized in stroke units substantially increased. In-hospital mortality decreased by 17.1% in patients with ischemic stroke. From 2008 to 2013, stroke mortality decreased, except for women between 45 and 64 years old and for people aged ≥85 years. An increase in cardiovascular risk factors and improved stroke management may explain the increase in the rates of patients hospitalized for ischemic stroke. The decrease observed for in-hospital stroke mortality may be because of recent improvements in acute-phase management. © 2017 American Heart Association, Inc.

Effect of a care plan based on Roy adaptation model biological dimension on stroke patients' physiologic adaptation level.

Science.gov (United States)

Alimohammadi, Nasrollah; Maleki, Bibi; Shahriari, Mohsen; Chitsaz, Ahmad

2015-01-01

Stroke is a stressful event with several functional, physical, psychological, social, and economic problems that affect individuals' different living balances. With coping strategies, patients try to control these problems and return to their natural life. The aim of this study is to investigate the effect of a care plan based on Roy adaptation model biological dimension on stroke patients' physiologic adaptation level. This study is a clinical trial in which 50 patients, affected by brain stroke and being admitted in the neurology ward of Kashani and Alzahra hospitals, were randomly assigned to control and study groups in Isfahan in 2013. Roy adaptation model care plan was administered in biological dimension in the form of four sessions and phone call follow-ups for 1 month. The forms related to Roy adaptation model were completed before and after intervention in the two groups. Chi-square test and t-test were used to analyze the data through SPSS 18. There was a significant difference in mean score of adaptation in physiological dimension in the study group after intervention (P adaptation in the patients affected by brain stroke in the study and control groups showed a significant increase in physiological dimension in the study group by 47.30 after intervention (P adaptation model biological dimension care plan can result in an increase in adaptation in patients with stroke in physiological dimension. Nurses can use this model for increasing patients' adaptation.

Impact of trichostatin A and sodium valproate treatment on post-stroke neurogenesis and behavioral outcomes in immature mice

Directory of Open Access Journals (Sweden)

Shanu eGeorge

2013-08-01

Full Text Available Stroke in the neonatal brain frequently results in neurologic impairments including cognitive disability. We investigated the effect of long-term sodium valproate (valproate and Trichostatin A (TSA treatment upon post-stroke neurogenesis in the dentate gyrus (DG of stroke-injured immature mice. Decreased or abnormal integration of newborn DG neurons into hippocampal circuits can result in impaired visual-spatial function, abnormal modulation of mood-related behaviors, and the development of post-stroke epilepsy. Unilateral carotid ligation of P12 CD1 mice was followed by treatment with valproate, TSA, or vehicle for 2 weeks, BrdU administration for measurement of neurogenesis, and perfusion at P42 or P60. Behavior testing was conducted from P38-42. No detrimental effects on behavior testing were noted with TSA treatment, but mildly impaired cognitive function was noted with valproate-treated injured animals compared to normal animals. Significant increases in DG neurogenesis with both TSA and valproate treatment were noted with later administration of BrdU. Increased mortality and impaired weight gain was noted in the valproate-treated ligated animals, but not in the TSA-treated animals. In summary, the impact of HDAC inhibition upon post-stroke SGZ neurogenesis is likely to depend on the age of the animal at the time point when neurogenesis is assessed, duration of HDAC inhibition before BrdU labeling, and/or the stage in the evolution of the injury.

Development of herpetic infection associated with stroke and its correction with acyclovir

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Gumenyuk Аlla

2017-03-01

Full Text Available Background: Herpes simplex virus (HSV is prevalent in today’s world population, and there is evidence of potential HSV reactivation in patients with immune deficiency induced by acute stroke. However, the data on the use of antivirals in the setting of stroke are scarce. The aim of this study was to evaluate the reactivation of HSV-1 in patients with stroke, using several methods, and to assess the efficacy of acyclovir in the treatment of experimental stroke. In the employed methodology, PCR and dot-ELISA were used to detect the occurrence of HSV-1 in patients with acute stroke. White mice were infected with HSV-1 and experimental stroke was simulated. The infected mice with stroke were subdivided into two groups: one of them received no treatment, while the other one was treated with acyclovir. The level of HSV-1 reactivation was determined by the methods used in human patients. The brain tissue of experimental animals was also subjected to morphological and morphometrical study. The results of such work reveal that, by the applied serological method, HSV-1 was found in all patients with stroke. Herein, the increased level of HSV-1 was seen in the brain tissue and blood in 100% of the experimental infected animals. However, the use of acyclovir suppressed reproduction of HSV-1. Hence, it can be concluded that clinical and laboratory studies have demonstrated the different sensitivity of Dot-Elisa and PCR, with the former being more sensitive. Moreover, the use of acyclovir in the experiment inhibited viral reproduction and further development of viral infection. Still, chemic lesions in the brain persisted.

Animal models of erectile dysfunction

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Snehlata V Gajbhiye

2015-01-01

Full Text Available Animal models have contributed to a great extent to understanding and advancement in the field of sexual medicine. Many current medical and surgical therapies in sexual medicine have been tried based on these animal models. Extensive literature search revealed that the compiled information is limited. In this review, we describe various experimental models of erectile dysfunction (ED encompassing their procedures, variables of assessment, advantages and disadvantages. The search strategy consisted of review of PubMed based articles. We included original research work and certain review articles available in PubMed database. The search terms used were "ED and experimental models," "ED and nervous stimulation," "ED and cavernous nerve stimulation," "ED and central stimulation," "ED and diabetes mellitus," "ED and ageing," "ED and hypercholesteremia," "ED and Peyronie′s disease," "radiation induced ED," "telemetric recording," "ED and mating test" and "ED and non-contact erection test."

Animal models for Gaucher disease research

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Tamar Farfel-Becker

2011-11-01

Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder (LSD, is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

Animal models for Gaucher disease research.

Science.gov (United States)

Farfel-Becker, Tamar; Vitner, Einat B; Futerman, Anthony H

2011-11-01

Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

Final model of multicriterionevaluation of animal welfare

DEFF Research Database (Denmark)

Bonde, Marianne; Botreau, R; Bracke, MBM

One major objective of Welfare Quality® is to propose harmonized methods for the overall assessment of animal welfare on farm and at slaughter that are science based and meet societal concerns. Welfare is a multidimensional concept and its assessment requires measures of different aspects. Welfar......, acceptable welfare and not classified. This evaluation model is tuned according to the views of experts from animal and social sciences, and stakeholders....... Quality® proposes a formal evaluation model whereby the data on animals or their environment are transformed into value scores that reflect compliance with 12 subcriteria and 4 criteria of good welfare. Each animal unit is then allocated to one of four categories: excellent welfare, enhanced welfare...

Retinal Cell Degeneration in Animal Models

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Masayuki Niwa

2016-01-01

Full Text Available The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced, autoimmune (experimental autoimmune encephalomyelitis, mechanical stress (optic nerve crush-induced, light-induced and ischemia (transient retinal ischemia-induced. The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage.

Animal Models of Hemophilia and Related Bleeding Disorders

Science.gov (United States)

Lozier, Jay N.; Nichols, Timothy C.

2013-01-01

Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467

Henipavirus Infections: Lessons from Animal Models

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Kévin P. Dhondt

2013-04-01

Full Text Available The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed.

Animal models of asthma: utility and limitations

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Aun MV

2017-11-01

Full Text Available Marcelo Vivolo Aun,1,2 Rafael Bonamichi-Santos,1,2 Fernanda Magalhães Arantes-Costa,2 Jorge Kalil,1 Pedro Giavina-Bianchi1 1Clinical Immunology and Allergy Division, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil, 2Laboratory of Experimental Therapeutics (LIM20, Department of Internal Medicine, University of Sao Paulo, Sao Paulo, Brazil Abstract: Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes

In-Hospital Risk Prediction for Post-stroke Depression. Development and Validation of the Post-stroke Depression Prediction Scale

NARCIS (Netherlands)

Thóra Hafsteinsdóttir; Roelof G.A. Ettema; Diederick Grobbee; Prof. Dr. Marieke J. Schuurmans; Janneke van Man-van Ginkel; Eline Lindeman

2013-01-01

Background and Purpose—The timely detection of post-stroke depression is complicated by a decreasing length of hospital stay. Therefore, the Post-stroke Depression Prediction Scale was developed and validated. The Post-stroke Depression Prediction Scale is a clinical prediction model for the early

N-3 polyunsaturated fatty acids in animal models with neuroinflammation: An update.

Science.gov (United States)

Trépanier, Marc-Olivier; Hopperton, Kathryn E; Orr, Sarah K; Bazinet, Richard P

2016-08-15

Neuroinflammation is a characteristic of a multitude of neurological and psychiatric disorders. Modulating inflammatory pathways offers a potential therapeutic target in these disorders. Omega-3 polyunsaturated fatty acids have anti-inflammatory and pro-resolving properties in the periphery, however, their effect on neuroinflammation is less studied. This review summarizes 61 animal studies that tested the effect of omega-3 polyunsaturated fatty acids on neuroinflammatory outcomes in vivo in various models including stroke, spinal cord injury, aging, Alzheimer's disease, Parkinson's disease, lipopolysaccharide and IL-1β injections, diabetes, neuropathic pain, traumatic brain injury, depression, surgically induced cognitive decline, whole body irradiation, amyotrophic lateral sclerosis, N-methyl-D-aspartate-induced excitotoxicity and lupus. The evidence presented in this review suggests anti-neuroinflammatory properties of omega-3 polyunsaturated fatty acids, however, it is not clear by which mechanism omega-3 polyunsaturated fatty acids exert their effect. Future research should aim to isolate the effect of omega-3 polyunsaturated fatty acids on neuroinflammatory signaling in vivo and elucidate the mechanisms underlying these effects. Copyright © 2016. Published by Elsevier B.V.

Results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial by stroke subtypes

DEFF Research Database (Denmark)

Amarenco, Pierre; Benavente, Oscar; Goldstein, Larry B

2009-01-01

BACKGROUND AND PURPOSE: The SPARCL trial showed that atorvastatin 80 mg/d reduces the risk of stroke and other cardiovascular events in patients with recent stroke or transient ischemic attack (TIA). We tested the hypothesis that the benefit of treatment varies according to index event stroke...... subtype. METHODS: Subjects with stroke or TIA without known coronary heart disease were randomized to atorvastatin 80 mg/d or placebo. The SPARCL primary end point was fatal or nonfatal stroke. Secondary end points included major cardiovascular events (MCVE; stroke plus major coronary events). Cox...... regression models testing for an interaction with treatment assignment were used to explore potential differences in efficacy based on stroke subtype. RESULTS: For subjects randomized to atorvastatin versus placebo, a primary end point occurred in 13.1% versus 18.6% of those classified as having large vessel...

Modeling individual animal histories with multistate capture–recapture models

Science.gov (United States)

Lebreton, Jean-Dominique; Nichols, James D.; Barker, Richard J.; Pradel, Roger; Spendelow, Jeffrey A.

2009-01-01

Many fields of science begin with a phase of exploration and description, followed by investigations of the processes that account for observed patterns. The science of ecology is no exception, and recent decades have seen a focus on understanding key processes underlying the dynamics of ecological systems. In population ecology, emphasis has shifted from the state variable of population size to the demographic processes responsible for changes in this state variable: birth, death, immigration, and emigration. In evolutionary ecology, some of these same demographic processes, rates of birth and death, are also the determinants of fitness. In animal population ecology, the estimation of state variables and their associated vital rates is especially problematic because of the difficulties in sampling such populations and detecting individual animals. Indeed, early capture–recapture models were developed for the purpose of estimating population size, given the reality that all animals are not caught or detected at any sampling occasion. More recently, capture–recapture models for open populations were developed to draw inferences about survival in the face of these same sampling problems. The focus of this paper is on multi‐state mark–recapture models (MSMR), which first appeared in the 1970s but have undergone substantial development in the last 15 years. These models were developed to deal explicitly with biological variation, in that animals in different “states” (classes defined by location, physiology, behavior, reproductive status, etc.) may have different probabilities of survival and detection. Animal transitions between states are also stochastic and themselves of interest. These general models have proven to be extremely useful and provide a way of thinking about a remarkably wide range of important ecological processes. These methods are now at a stage of refinement and sophistication where they can readily be used by biologists to tackle a wide

mStroke: "Mobile Stroke"-Improving Acute Stroke Care with Smartphone Technology.

Science.gov (United States)

Andrew, Benjamin Y; Stack, Colleen M; Yang, Julian P; Dodds, Jodi A

2017-07-01

This study aimed to evaluate the effect of method and time of system activation on clinical metrics in cases utilizing the Stop Stroke (Pulsara, Inc.) mobile acute stroke care coordination application. A retrospective cohort analysis of stroke codes at 12 medical centers using Stop Stroke from March 2013 to May 2016 was performed. Comparison of metrics (door-to-needle time [DTN] and door-to-CT time [DTC], and rate of DTN ≤ 60 minutes [goal DTN]) was performed between subgroups based on method (emergency medical service [EMS] versus emergency department [ED]) and time of activation. Effects were adjusted for confounders (age, sex, National Institutes of Health Stroke Scale [NIHSS] score) using multiple linear and logistic regression. The final dataset included 2589 cases. Cases activated by EMS were more severe (median NIHSS score 8 versus 4, P technology provides unique insight into acute stroke codes. Activation of mobile electronic stroke coordination in the field appears to promote a more expedited and successful care process. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Animal model of thermal injuries

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F. Bečić

2003-11-01

Full Text Available Experimental studies of burns require the use of different animal models with the aim to imitate and reproduce pathophysiological conditions. The aim of this work was to establish experimental model of thermal injury.New Zealand rabbits, weighted from 1.8 kg to 2.3 kg, were utilised during our study. Another, also utilized, animal types were laboratory Rattus rats, species Wistar, albino type, females with body weight of about 232 g. All animals were from our own litter (Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine in Sarajevo. During the experiment, animal were properly situated in adequate cages and rooms, at the controlled temperature (22 ± 2°C, and in the air with normal humidity level. All animals took food and water ad libitum.Rabbits received anesthesia - intravenous pentobarbital sodium in a dose of 60 mg/kg, and then, hair from the upper side of the each rabbit ear was removed and burns were caused by a metal seal in the same manner as in rats. Rats were primarily anesthesied by intraperitoneal pentobarbital sodium in a dose of 35 mg/kg, and then, their hair was removed from the scapula zone (5 cm x 5 cm. Burns were caused by contact with a round metal seal, heated at 80°C in a water bath, during the period of 14 seconds together with contact thermometer control. Round metal seal (radius: 2.5 cm; weight: 100 g; surface: 5 cm2 was just placed on the rat skin without any additional pressure. In order to maintain the microcirculation in the burn wound and to reduce the conversion of partial-thickness skin burns to the burns of the full-thickness skin, all burn wounds were immediately sunk in the 4°C water. Subsequent to that procedure, all animals were individually situated in the proper cages, and left to rest for 4 hours with a constant cautious monitoring of the wound development and animal general state.

Animal models of drug addiction.

Science.gov (United States)

García Pardo, María Pilar; Roger Sánchez, Concepción; De la Rubia Ortí, José Enrique; Aguilar Calpe, María Asunción

2017-09-29

The development of animal models of drug reward and addiction is an essential factor for progress in understanding the biological basis of this disorder and for the identification of new therapeutic targets. Depending on the component of reward to be studied, one type of animal model or another may be used. There are models of reinforcement based on the primary hedonic effect produced by the consumption of the addictive substance, such as the self-administration (SA) and intracranial self-stimulation (ICSS) paradigms, and there are models based on the component of reward related to associative learning and cognitive ability to make predictions about obtaining reward in the future, such as the conditioned place preference (CPP) paradigm. In recent years these models have incorporated methodological modifications to study extinction, reinstatement and reconsolidation processes, or to model specific aspects of addictive behavior such as motivation to consume drugs, compulsive consumption or drug seeking under punishment situations. There are also models that link different reinforcement components or model voluntary motivation to consume (two-bottle choice, or drinking in the dark tests). In short, innovations in these models allow progress in scientific knowledge regarding the different aspects that lead individuals to consume a drug and develop compulsive consumption, providing a target for future treatments of addiction.

Osteoarthritis: New Insights in Animal Models

OpenAIRE

Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human ‘idiopathic’ OA, with late onset and slow progression, it is perha...

Analysis of CD45- [CD34+/KDR+] endothelial progenitor cells as juvenile protective factors in a rat model of ischemic-hemorrhagic stroke.

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Julius L Decano

Full Text Available Identification of juvenile protective factors (JPFs which are altered with age and contribute to adult-onset diseases could identify novel pathways for reversing the effects of age, an accepted non-modifiable risk factor to adult-onset diseases. Since endothelial progenitor cells (EPCs have been observed to be altered in stroke, hypertension and hypercholesterolemia, said EPCs are candidate JPFs for adult-onset stroke. A priori, if EPC aging plays a 'master-switch JPF-role' in stroke pathogenesis, juvenile EPC therapy alone should delay stroke-onset. Using a hypertensive, transgenic-hyperlipidemic rat model of spontaneous ischemic-hemorrhagic stroke, spTg25, we tested the hypothesis that freshly isolated juvenile EPCs are JPFs that can attenuate stroke progression and delay stroke onset.FACS analysis revealed that CD45- [CD34+/KDR+] EPCs decrease with progression to stroke in spTg25 rats, exhibit differential expression of the dual endodthelin-1/VEGFsp receptor (DEspR and undergo differential DEspR-subtype specific changes in number and in vitro angiogenic tube-incorporation. In vivo EPC infusion of male, juvenile non-expanded cd45-[CD34+/KDR+] EPCs into female stroke-prone rats prior to stroke attenuated progression and delayed stroke onset (P<0.003. Detection of Y-chromosome DNA in brain microvessels of EPC-treated female spTg25 rats indicates integration of male EPCs into female rat brain microvessels. Gradient-echo MRI showed delay of ischemic-hemorrhagic lesions in EPC-treated rats. Real-time RT-PCR pathway-specific array-analysis revealed age-associated gene expression changes in CD45-[CD34+/KDR]EPC subtypes, which were accelerated in stroke-prone rats. Pro-angiogenic genes implicated in intimal hyperplasia were increased in stroke-prone rat EPCs (P<0.0001, suggesting a maladaptive endothelial repair system which acts like a double-edged sword repairing while predisposing to age-associated intimal hyperplasia.Altogether, the data

Basic mechanisms of MCD in animal models.

Science.gov (United States)

Battaglia, Giorgio; Becker, Albert J; LoTurco, Joseph; Represa, Alfonso; Baraban, Scott C; Roper, Steven N; Vezzani, Annamaria

2009-09-01

Epilepsy-associated glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) and highly differentiated glioneuronal tumors, most frequently gangliogliomas. The neuropathological findings are variable but suggest aberrant proliferation, migration, and differentiation of neural precursor cells as essential pathogenetic elements. Recent advances in animal models for MCDs allow new insights in the molecular pathogenesis of these epilepsy-associated lesions. Novel approaches, presented here, comprise RNA interference strategies to generate and study experimental models of subcortical band heterotopia and study functional aspects of aberrantly shaped and positioned neurons. Exciting analyses address impaired NMDA receptor expression in FCD animal models compared to human FCDs and excitatory imbalances in MCD animal models such as lissencephaly gene ablated mice as well as in utero irradiated rats. An improved understanding of relevant pathomechanisms will advance the development of targeted treatment strategies for epilepsy-associated malformations.

The Impacts of Peptic Ulcer on Stroke Recurrence.

Science.gov (United States)

Xu, Zongliang; Wang, Ling; Lin, Ying; Wang, Zhaojun; Zhang, Yun; Li, Junrong; Li, Shenghua; Ye, Zusen; Yuan, Kunxiong; Shan, Wanying; Liu, Xinfeng; Fan, Xinying; Xu, Gelin

2018-04-10

Peptic ulcer has been associated with an increased risk of stroke. This study aimed to evaluate the impacts of peptic ulcer on stroke recurrence and mortality. Patients with first-ever ischemic stroke were retrospectively confirmed with or without a history of peptic ulcer. The primary end point was defined as fatal and nonfatal stroke recurrence. Risks of 1-year fatal and nonfatal stroke recurrence were analyzed with the Kaplan-Meier method. Predictors of fatal and nonfatal stroke recurrence were evaluated with the Cox proportional hazards model. Among the 2577 enrolled patients with ischemic stroke, 129 (5.0%) had a history of peptic ulcer. The fatal and nonfatal stroke recurrence within 1 year of the index stroke was higher in patients with peptic ulcer than in patients without peptic ulcer (12.4% versus 7.2%, P = .030). Cox proportional hazards model detected that age (hazard ratio [HR] = 1.018, 95% confidence interval [CI] 1.005-1.031, P = .008), hypertension (HR = 1.397, 95% CI 1.017-1.918, P = .039), and history of peptic ulcer (HR = 1.853, 95% CI 1.111-3.091, P = .018) were associated with stroke recurrence. Ischemic stroke patients with peptic ulcer may have an increased risk of stroke recurrence. The results emphasize the importance of appropriate prevention and management of peptic ulcer for secondary stroke prevention. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Osteoporotic Animal Models of Bone Healing: Advantages and Pitfalls.

Science.gov (United States)

Calciolari, Elena; Donos, Nikolaos; Mardas, Nikos

2017-10-01

The aim of this review was to summarize the advantages and pitfalls of the available osteoporotic animal models of bone healing. A thorough literature search was performed in MEDLINE via OVID and EMBASE to identify animal studies investigating the effect of experimental osteoporosis on bone healing and bone regeneration. The osteotomy model in the proximal tibia is the most popular osseous defect model to study the bone healing process in osteoporotic-like conditions, although other well-characterized models, such as the post-extraction model, might be taken into consideration by future studies. The regenerative potential of osteoporotic bone and its response to biomaterials/regenerative techniques has not been clarified yet, and the critical size defect model might be an appropriate tool to serve this purpose. Since an ideal animal model for simulating osteoporosis does not exist, the type of bone remodeling, the animal lifespan, the age of peak bone mass, and the economic and ethical implications should be considered in our selection process. Furthermore, the influence of animal species, sex, age, and strain on the outcome measurement should be taken into account. In order to make future studies meaningful, standardized international guidelines for osteoporotic animal models of bone healing need to be set up.

Association between atherogenic dyslipidemia and recurrent stroke risk in patients with different subtypes of ischemic stroke.

Science.gov (United States)

Zhao, Lu; Wang, Ruihao; Song, Bo; Tan, Song; Gao, Yuan; Fang, Hui; Lu, Jie; Xu, Yuming

2015-07-01

The association between atherogenic dyslipidemia and stroke recurrence remains unclear, and may be influenced by different subtypes of ischemic stroke. We aimed to investigate whether atherogenic dyslipidemia contributed to stroke recurrence in ischemic stroke patients and in those with certain subtypes of ischemic stroke. We conducted a prospective hospital-based study enrolling patients with acute ischemic stroke. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol dyslipidemia and stroke recurrence was analyzed by using multivariable Cox regression model. In the 510 ischemic stroke patients, 64 patients (12·5%) had atherogenic dyslipidemia, and 66 patients (12·9%) experienced stroke recurrence events within 24 months. Kaplan-Meier analysis revealed that stroke recurrence rate was significantly higher in patients with atherogenic dyslipidemia than those without in all the stroke patients (20·3% vs. 11·9%; P = 0·048), and more evident in those of large-artery atherosclerosis subtype (31·0% vs. 14·1%; P = 0·014), but not in the other subtypes. Multivariable Cox regression analysis revealed that atherogenic dyslipidemia was associated with higher stroke recurrence risk among stroke patients of large-artery atherosclerosis subtype (hazard ratio, 2·79; 95% confidence interval, 1·24-6·28), but not significant in all the stroke patients (hazard ratio, 1·69; 95% confidence interval, 0·85-3·37). Atherogenic dyslipidemia is associated with higher risk of stroke recurrence in ischemic stroke patients. Such association might be more pronounced in large-artery atherosclerosis subtype and needs further investigation to establish such relationship. © 2015 World Stroke Organization.

Effective Education Materials to Advance Stroke Awareness Without Teacher Participation in Junior High School Students.

Science.gov (United States)

Ohyama, Satoshi; Yokota, Chiaki; Miyashita, Fumio; Amano, Tatsuo; Inoue, Yasuteru; Shigehatake, Yuya; Sakamoto, Yuki; Toyoda, Kazunori; Minematsu, Kazuo

2015-11-01

Youth stroke education is promising for the spread of stroke awareness. The aim of this study was to examine whether our stroke awareness teaching materials without teacher's participation can increase student awareness to act fast on suspected stroke signs. We used the face, arm, speech, and time (FAST) mnemonic derived from the Cincinnati Prehospital Stroke Scale. Seventy-three students of the second grade and 72 students of the third grade (age range, 13-15 years) in a junior high school were enrolled in the study. The students were divided into 2 groups: students who received a teacher's lesson (group I) and those who did not receive a teacher's lesson (group II). Students in group II watched an animated cartoon and read a Manga comic in class. All students took the educational aids home, including the Manga comic and magnetic posters printed with the FAST message. Questionnaires on stroke knowledge were examined at baseline and immediately and 3 months after receiving the intervention. At 3 months after the intervention, a significant improvement in understanding the FAST message was confirmed in both the groups (group I, 85%; group II, 94%). Significant increases in the knowledge of risk factors were not observed in each group. Our education materials include a Manga comic, an animated cartoon, and a magnetic poster, without an accompanying teacher's lesson can increase stroke awareness, including the FAST message, in junior high school students. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Consideration of Strategies to Improve the Value of Animal Models.

Science.gov (United States)

Herati, Ramin Sedaghat; Wherry, E John

2018-04-02

Animal models are an essential feature of the vaccine design toolkit. Although animal models have been invaluable in delineating the mechanisms of immune function, their precision in predicting how well specific vaccines work in humans is often suboptimal. There are, of course, many obvious species differences that may limit animal models from predicting all details of how a vaccine works in humans. However, careful consideration of which animal models may have limitations should also allow more accurate interpretations of animal model data and more accurate predictions of what is to be expected in clinical trials. In this article, we examine some of the considerations that might be relevant to cross-species extrapolation of vaccine-related immune responses for the prediction of how vaccines will perform in humans. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Pediatric Stroke

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... and Patient Resources Home » Patients & Families » About Stroke » Pediatric Stroke » Introduction Introduction What is a Stroke? Ischemic Stroke Intracerebral Hemorrhage Subarachnoid Hemorrhage Pediatric Stroke Introduction Types of Stroke Diagnosis and Treatment ...

Lateral dynamic flight stability of a model hoverfly in normal and inclined stroke-plane hovering

International Nuclear Information System (INIS)

Xu, Na; Sun, Mao

2014-01-01

Many insects hover with their wings beating in a horizontal plane (‘normal hovering’), while some insects, e.g., hoverflies and dragonflies, hover with inclined stroke-planes. Here, we investigate the lateral dynamic flight stability of a hovering model hoverfly. The aerodynamic derivatives are computed using the method of computational fluid dynamics, and the equations of motion are solved by the techniques of eigenvalue and eigenvector analysis. The following is shown: The flight of the insect is unstable at normal hovering (stroke-plane angle equals 0) and the instability becomes weaker as the stroke-plane angle increases; the flight becomes stable at a relatively large stroke-plane angle (larger than about 24°). As previously shown, the instability at normal hovering is due to a positive roll-moment/side-velocity derivative produced by the ‘changing-LEV-axial-velocity’ effect. When the stroke-plane angle increases, the wings bend toward the back of the body, and the ‘changing-LEV-axial-velocity’ effect decreases; in addition, another effect, called the ‘changing-relative-velocity’ effect (the ‘lateral wind’, which is due to the side motion of the insect, changes the relative velocity of its wings), becomes increasingly stronger. This causes the roll-moment/side-velocity derivative to first decrease and then become negative, resulting in the above change in stability as a function of the stroke-plane angle. (paper)

Reviewing model application to support animal health decision making.

Science.gov (United States)

Singer, Alexander; Salman, Mo; Thulke, Hans-Hermann

2011-04-01

Animal health is of societal importance as it affects human welfare, and anthropogenic interests shape decision making to assure animal health. Scientific advice to support decision making is manifold. Modelling, as one piece of the scientific toolbox, is appreciated for its ability to describe and structure data, to give insight in complex processes and to predict future outcome. In this paper we study the application of scientific modelling to support practical animal health decisions. We reviewed the 35 animal health related scientific opinions adopted by the Animal Health and Animal Welfare Panel of the European Food Safety Authority (EFSA). Thirteen of these documents were based on the application of models. The review took two viewpoints, the decision maker's need and the modeller's approach. In the reviewed material three types of modelling questions were addressed by four specific model types. The correspondence between tasks and models underpinned the importance of the modelling question in triggering the modelling approach. End point quantifications were the dominating request from decision makers, implying that prediction of risk is a major need. However, due to knowledge gaps corresponding modelling studies often shed away from providing exact numbers. Instead, comparative scenario analyses were performed, furthering the understanding of the decision problem and effects of alternative management options. In conclusion, the most adequate scientific support for decision making - including available modelling capacity - might be expected if the required advice is clearly stated. Copyright © 2011 Elsevier B.V. All rights reserved.

Harnessing the potential of biomaterials for brain repair after stroke

Science.gov (United States)

Tuladhar, Anup; Payne, Samantha L.; Shoichet, Molly S.

2018-03-01

Stroke is a devastating disease for which no clinical treatment exists to regenerate lost tissue. Strategies for brain repair in animal models of stroke include the delivery of drug or cell-based therapeutics; however, the complex anatomy and functional organization of the brain presents many challenges. Biomaterials may alleviate some of these challenges by providing a scaffold, localizing the therapy to the site of action, and/or modulating cues to brain cells. Here, the challenges associated with delivery of therapeutics to the brain and the biomaterial strategies used to overcome these challenges are described. For example, innovative hydrogel delivery systems have been designed to provide sustained trophic factor delivery for endogenous repair and to support transplanted cell survival and integration. Novel treatments, such as electrical stimulation of transplanted cells and the delivery of factors for the direct reprogramming of astrocytes into neurons, may be further enhanced by biomaterial delivery systems. Ultimately, improved clinical translation will be achieved by combining clinically relevant therapies with biomaterials strategies.

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

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Beretta, Simone; Versace, Alessandro; Carone, Davide; Riva, Matteo; Dell'Era, Valentina; Cuccione, Elisa; Cai, Ruiyao; Monza, Laura; Pirovano, Silvia; Padovano, Giada; Stiro, Fabio; Presotto, Luca; Paternò, Giovanni; Rossi, Emanuela; Giussani, Carlo; Sganzerla, Erik P; Ferrarese, Carlo

2017-10-01

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

Classic and New Animal Models of Parkinson's Disease

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Javier Blesa

2012-01-01

Full Text Available Neurological disorders can be modeled in animals so as to recreate specific pathogenic events and behavioral outcomes. Parkinson’s Disease (PD is the second most common neurodegenerative disease of an aging population, and although there have been several significant findings about the PD disease process, much of this process still remains a mystery. Breakthroughs in the last two decades using animal models have offered insights into the understanding of the PD disease process, its etiology, pathology, and molecular mechanisms. Furthermore, while cellular models have helped to identify specific events, animal models, both toxic and genetic, have replicated almost all of the hallmarks of PD and are useful for testing new neuroprotective or neurorestorative strategies. Moreover, significant advances in the modeling of additional PD features have come to light in both classic and newer models. In this review, we try to provide an updated summary of the main characteristics of these models as well as the strengths and weaknesses of what we believe to be the most popular PD animal models. These models include those produced by 6-hydroxydopamine (6-OHDA, 1-methyl-1,2,3,6-tetrahydropiridine (MPTP, rotenone, and paraquat, as well as several genetic models like those related to alpha-synuclein, PINK1, Parkin and LRRK2 alterations.

Stroke Risk Perception in Atrial Fibrillation Patients is not Associated with Clinical Stroke Risk.

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Fournaise, Anders; Skov, Jane; Bladbjerg, Else-Marie; Leppin, Anja

2015-11-01

Clinical risk stratification models, such as the CHA2DS2-VASc, are used to assess stroke risk in atrial fibrillation (AF) patients. No study has yet investigated whether and to which extent these patients have a realistic perception of their personal stroke risk. The purpose of this study was to investigate and describe the association between AF patients' stroke risk perception and clinical stroke risk. In an observational cross-sectional study design, we surveyed 178 AF patients with a mean age of 70.6 years (SD 8.3) in stable anticoagulant treatment (65% treatment duration >12 months). Clinical stroke risk was scored through the CHA2DS2-VASc, and patients rated their perceived personal stroke risk on a 7-point Likert scale. There was no significant association between clinical stroke risk assessment and patients' stroke risk perception (rho = .025; P = .741). Approximately 60% of the high-risk patients had an unrealistic perception of their own stroke risk, and there was no significant increase in risk perception from those with a lower compared with a higher risk factor load (χ(2) = .010; P = .522). Considering possible negative implications in terms of lack of motivation for lifestyle behavior change and adequate adherence to the treatment and monitoring of vitamin K antagonist, the apparent underestimation of risk by large subgroups warrants attention and needs further investigation with regard to possible behavioral consequences. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Generating and measuring photochemical changes inside the brain using optical fibers: exploring stroke.

Science.gov (United States)

Tsiminis, Georgios; Klarić, Thomas S; Schartner, Erik P; Warren-Smith, Stephen C; Lewis, Martin D; Koblar, Simon A; Monro, Tanya M

2014-11-01

We report here on the development of a method for inducing a stroke in a specific location within a mouse brain through the use of an optical fiber. By capturing the emitted fluorescence signal generated using the same fiber it is possible to monitor photochemical changes within the brain in real-time, and directly measure the concentration of the stroke-inducing dye, Rose Bengal, at the infarct site. This technique reduces the requirement for post-operative histology to determine if a stroke has successfully been induced within the animal, and therefore opens up the opportunity to explore the recovery of the brain after the stroke event.

Acupuncture therapy for stroke patients.

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Li, Xin; Wang, Qiang

2013-01-01

Acupuncture is one of the most important parts of Traditional Chinese Medicine, has been used for more than 3000 years as prevention and treatment for various diseases in China as well as in adjacent regions, and is widely accepted in western countries in recent years. More and more clinical trials revealed that acupuncture shows positive effect in stroke, not only as a complementary and alternative medicine for poststroke rehabilitation but also as a preventive strategy which could induce cerebral ischemic tolerance, especially when combined with modern electrotherapy. Acupuncture has some unique characteristics, which include acupoint specificity and parameter-dependent effect. It also involves complicated mechanism to exert the beneficial effect on stroke. Series of clinical trials have shown that acupuncture primarily regulates the release of neurochemicals, hemorheology, cerebral microcirculation, metabolism, neuronal activity, and the function of specific brain region. Animal studies showed that the effects of acupuncture therapy on stroke were possibly via inhibition of postischemic inflammatory reaction, stimulation of neurogenesis and angiogenesis, and influence on neural plasticity. Mechanisms for its preconditioning effect include activity enhancement of antioxidant, regulation of the endocannabinoid system, and inhibition of apoptosis. Although being controversial, acupuncture is a promising preventive and treatment strategy for stroke, but further high-quality clinical trials would be needed to provide more confirmative evidence. © 2013 Elsevier Inc. All rights reserved.

Elementary of animal model for percutaneous and ocular penetration

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Kalpesh Chhotalal Ashara

2016-12-01

Full Text Available Models of animal are the most appropriate method for assessments of human in-vivo percutaneous and ocular penetrations. Monkey and rodents are used for the same. There are several nuts and bolts of each one, so it is necessary to study each one separately. Monkey, porcine and guinea pig penetration are correlated with that of human skin. The skin of rodents, lupus, pigs, etc. has more penetration properties than human skin. Rabbit, goat and sheep eye are mostly used for ocular penetration. The researcher also used hen’s egg chorioallantoic membrane test for ocular irritation study. The other animals’ cornea, cul-de-sac, eyeballs and prepared corneal epithelial models are very less in practice. Web-based alternative non-animal models are also available instead of animal models too. This article describes characteristics of monkeys, pigs, rats, rabbits, guinea pigs and hairless rodents, HuSki model, Cellophane® membrane, egg membrane, gelatin membrane, animal models for ophthalmic delivery, hen’s egg chorioallantoic membrane test, prepared corneal epithelial models and web-based alternative non-animal database.

Ischemic stroke destabilizes circadian rhythms

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Borjigin Jimo

2008-10-01

Full Text Available Abstract Background The central circadian pacemaker is a remarkably robust regulator of daily rhythmic variations of cardiovascular, endocrine, and neural physiology. Environmental lighting conditions are powerful modulators of circadian rhythms, but regulation of circadian rhythms by disease states is less clear. Here, we examine the effect of ischemic stroke on circadian rhythms in rats using high-resolution pineal microdialysis. Methods Rats were housed in LD 12:12 h conditions and monitored by pineal microdialysis to determine baseline melatonin timing profiles. After demonstration that the circadian expression of melatonin was at steady state, rats were subjected to experimental stroke using two-hour intralumenal filament occlusion of the middle cerebral artery. The animals were returned to their cages, and melatonin monitoring was resumed. The timing of onset, offset, and duration of melatonin secretion were calculated before and after stroke to determine changes in circadian rhythms of melatonin secretion. At the end of the monitoring period, brains were analyzed to determine infarct volume. Results Rats demonstrated immediate shifts in melatonin timing after stroke. We observed a broad range of perturbations in melatonin timing in subsequent days, with rats exhibiting onset/offset patterns which included: advance/advance, advance/delay, delay/advance, and delay/delay. Melatonin rhythms displayed prolonged instability several days after stroke, with a majority of rats showing a day-to-day alternation between advance and delay in melatonin onset and duration. Duration of melatonin secretion changed in response to stroke, and this change was strongly determined by the shift in melatonin onset time. There was no correlation between infarct size and the direction or amplitude of melatonin phase shifting. Conclusion This is the first demonstration that stroke induces immediate changes in the timing of pineal melatonin secretion, indicating

Magnetic Particle Imaging for Real-Time Perfusion Imaging in Acute Stroke.

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Ludewig, Peter; Gdaniec, Nadine; Sedlacik, Jan; Forkert, Nils D; Szwargulski, Patryk; Graeser, Matthias; Adam, Gerhard; Kaul, Michael G; Krishnan, Kannan M; Ferguson, R Matthew; Khandhar, Amit P; Walczak, Piotr; Fiehler, Jens; Thomalla, Götz; Gerloff, Christian; Knopp, Tobias; Magnus, Tim

2017-10-24

The fast and accurate assessment of cerebral perfusion is fundamental for the diagnosis and successful treatment of stroke patients. Magnetic particle imaging (MPI) is a new radiation-free tomographic imaging method with a superior temporal resolution, compared to other conventional imaging methods. In addition, MPI scanners can be built as prehospital mobile devices, which require less complex infrastructure than computed tomography (CT) and magnetic resonance imaging (MRI). With these advantages, MPI could accelerate the stroke diagnosis and treatment, thereby improving outcomes. Our objective was to investigate the capabilities of MPI to detect perfusion deficits in a murine model of ischemic stroke. Cerebral ischemia was induced by inserting of a microfilament in the internal carotid artery in C57BL/6 mice, thereby blocking the blood flow into the medial cerebral artery. After the injection of a contrast agent (superparamagnetic iron oxide nanoparticles) specifically tailored for MPI, cerebral perfusion and vascular anatomy were assessed by the MPI scanner within seconds. To validate and compare our MPI data, we performed perfusion imaging with a small animal MRI scanner. MPI detected the perfusion deficits in the ischemic brain, which were comparable to those with MRI but in real-time. For the first time, we showed that MPI could be used as a diagnostic tool for relevant diseases in vivo, such as an ischemic stroke. Due to its shorter image acquisition times and increased temporal resolution compared to that of MRI or CT, we expect that MPI offers the potential to improve stroke imaging and treatment.

Computer-animated model of accommodation and presbyopia.

Science.gov (United States)

Goldberg, Daniel B

2015-02-01

To understand, demonstrate, and further research the mechanisms of accommodation and presbyopia. Private practice, Little Silver, New Jersey, USA. Experimental study. The CAMA 2.0 computer-animated model of accommodation and presbyopia was produced in collaboration with an experienced medical animator using Autodesk Maya animation software and Adobe After Effects. The computer-animated model demonstrates the configuration and synchronous movements of all accommodative elements. A new classification of the zonular apparatus based on structure and function is proposed. There are 3 divisions of zonular fibers; that is, anterior, crossing, and posterior. The crossing zonular fibers form a scaffolding to support the lens; the anterior and posterior zonular fibers work reciprocally to achieve focused vision. The model demonstrates the important support function of Weiger ligament. Dynamic movement of the ora serrata demonstrates that the forces of ciliary muscle contraction store energy for disaccommodation in the elastic choroid. The flow of aqueous and vitreous provides strong evidence for our understanding of the hydrodynamic interactions during the accommodative cycle. The interaction may result from the elastic stretch in the choroid transmitted to the vitreous rather than from vitreous pressue. The model supports the concept that presbyopia results from loss of elasticity and increasing ocular rigidity in both the lenticular and extralenticular structures. The computer-animated model demonstrates the structures of accommodation moving in synchrony and might enhance understanding of the mechanisms of accommodation and presbyopia. Dr. Goldberg is a consultant to Acevision, Inc., and Bausch & Lomb. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Animal models in plastic and reconstructive surgery simulation-a review.

Science.gov (United States)

Loh, Charles Yuen Yung; Wang, Aline Yen Ling; Tiong, Vincent Tze Yang; Athanassopoulos, Thanassi; Loh, Meiling; Lim, Philip; Kao, Huang-Kai

2018-01-01

The use of live and cadaveric animal models in surgical training is well established as a means of teaching and improving surgical skill in a controlled setting. We aim to review, evaluate, and summarize the models published in the literature that are applicable to Plastic Surgery training. A PubMed search for keywords relating to animal models in Plastic Surgery and the associated procedures was conducted. Animal models that had cross over between specialties such as microsurgery with Neurosurgery and pinnaplasty with ear, nose, and throat surgery were included as they were deemed to be relevant to our training curriculum. A level of evidence and recommendation assessment was then given to each surgical model. Our review found animal models applicable to plastic surgery training in four major categories namely-microsurgery training, flap raising, facial surgery, and hand surgery. Twenty-four separate articles described various methods of practicing microsurgical techniques on different types of animals. Fourteen different articles each described various methods of conducting flap-based procedures which consisted of either local or perforator flap dissection. Eight articles described different models for practicing hand surgery techniques. Finally, eight articles described animal models that were used for head and neck procedures. A comprehensive summary of animal models related to plastic surgery training has been compiled. Cadaveric animal models provide a readily available introduction to many procedures and ought to be used instead of live models when feasible. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress and adaptation : Toward ecologically relevant animal models

NARCIS (Netherlands)

Koolhaas, Jaap M.; Boer, Sietse F. de; Buwalda, Bauke

Animal models have contributed considerably to the current understanding of mechanisms underlying the role of stress in health and disease. Despite the progress made already, much more can be made by more carefully exploiting animals' and humans' shared biology, using ecologically relevant models.

Identification of Sleep-Modulated Pathways Involved in Neuroprotection from Stroke.

Science.gov (United States)

Pace, Marta; Baracchi, Francesca; Gao, Bo; Bassetti, Claudio

2015-11-01

Sleep deprivation (SDp) performed before stroke induces an ischemic tolerance state as observed in other forms of preconditioning. As the mechanisms underlying this effect are not well understood, we used DNA oligonucleotide microarray analysis to identify the genes and the gene-pathways underlying SDp preconditioning effects. Gene expression was analyzed 3 days after stroke in 4 experimental groups: (i) SDp performed before focal cerebral ischemia (IS) induction; (ii) SDp performed before sham surgery; (iii) IS without SDp; and (iv) sham surgery without SDp. SDp was performed by gentle handling during the last 6 h of the light period, and ischemia was induced immediately after. Basic sleep research laboratory. Stroke induced a massive alteration in gene expression both in sleep deprived and non-sleep deprived animals. However, compared to animals that underwent ischemia alone, SDp induced a general reduction in transcriptional changes with a reduction in the upregulation of genes involved in cell cycle regulation and immune response. Moreover, an upregulation of a new neuroendocrine pathway which included melanin concentrating hormone, glycoprotein hormones-α-polypeptide and hypocretin was observed exclusively in rats sleep deprived before stroke. Our data indicate that sleep deprivation before stroke reprogrammed the signaling response to injury. The inhibition of cell cycle regulation and inflammation are neuroprotective mechanisms reported also for other forms of preconditioning treatment, whereas the implication of the neuroendocrine function is novel and has never been described before. These results therefore provide new insights into neuroprotective mechanisms involved in ischemic tolerance mechanisms. © 2015 Associated Professional Sleep Societies, LLC.

Lost Productivity in Stroke Survivors: An Econometrics Analysis.

Science.gov (United States)

Vyas, Manav V; Hackam, Daniel G; Silver, Frank L; Laporte, Audrey; Kapral, Moira K

2016-01-01

Stroke leads to a substantial societal economic burden. Loss of productivity among stroke survivors is a significant contributor to the indirect costs associated with stroke. We aimed to characterize productivity and factors associated with employability in stroke survivors. We used the Canadian Community Health Survey 2011-2012 to identify stroke survivors and employment status. We used multivariable logistic models to determine the impact of stroke on employment and on factors associated with employability, and used Heckman models to estimate the effect of stroke on productivity (number of hours worked/week and hourly wages). We included data from 91,633 respondents between 18 and 70 years and identified 923 (1%) stroke survivors. Stroke survivors were less likely to be employed (adjusted OR 0.39, 95% CI 0.33-0.46) and had hourly wages 17.5% (95% CI 7.7-23.7) lower compared to the general population, although there was no association between work hours and being a stroke survivor. We found that factors like older age, not being married, and having medical comorbidities were associated with lower odds of employment in stroke survivors in our sample. Stroke survivors are less likely to be employed and they earn a lower hourly wage than the general population. Interventions such as dedicated vocational rehabilitation and policies targeting return to work could be considered to address this lost productivity among stroke survivors. © 2016 S. Karger AG, Basel.

Network interactions underlying mirror feedback in stroke: A dynamic causal modeling study

Directory of Open Access Journals (Sweden)

Soha Saleh

2017-01-01

Full Text Available Mirror visual feedback (MVF is potentially a powerful tool to facilitate recovery of disordered movement and stimulate activation of under-active brain areas due to stroke. The neural mechanisms underlying MVF have therefore been a focus of recent inquiry. Although it is known that sensorimotor areas can be activated via mirror feedback, the network interactions driving this effect remain unknown. The aim of the current study was to fill this gap by using dynamic causal modeling to test the interactions between regions in the frontal and parietal lobes that may be important for modulating the activation of the ipsilesional motor cortex during mirror visual feedback of unaffected hand movement in stroke patients. Our intent was to distinguish between two theoretical neural mechanisms that might mediate ipsilateral activation in response to mirror-feedback: transfer of information between bilateral motor cortices versus recruitment of regions comprising an action observation network which in turn modulate the motor cortex. In an event-related fMRI design, fourteen chronic stroke subjects performed goal-directed finger flexion movements with their unaffected hand while observing real-time visual feedback of the corresponding (veridical or opposite (mirror hand in virtual reality. Among 30 plausible network models that were tested, the winning model revealed significant mirror feedback-based modulation of the ipsilesional motor cortex arising from the contralesional parietal cortex, in a region along the rostral extent of the intraparietal sulcus. No winning model was identified for the veridical feedback condition. We discuss our findings in the context of supporting the latter hypothesis, that mirror feedback-based activation of motor cortex may be attributed to engagement of a contralateral (contralesional action observation network. These findings may have important implications for identifying putative cortical areas, which may be targeted with

Stroke type differentiation using spectrally constrained multifrequency EIT: evaluation of feasibility in a realistic head model

International Nuclear Information System (INIS)

Malone, Emma; Jehl, Markus; Arridge, Simon; Betcke, Timo; Holder, David

2014-01-01

We investigate the application of multifrequency electrical impedance tomography (MFEIT) to imaging the brain in stroke patients. The use of MFEIT could enable early diagnosis and thrombolysis of ischaemic stroke, and therefore improve the outcome of treatment. Recent advances in the imaging methodology suggest that the use of spectral constraints could allow for the reconstruction of a one-shot image. We performed a simulation study to investigate the feasibility of imaging stroke in a head model with realistic conductivities. We introduced increasing levels of modelling errors to test the robustness of the method to the most common sources of artefact. We considered the case of errors in the electrode placement, spectral constraints, and contact impedance. The results indicate that errors in the position and shape of the electrodes can affect image quality, although our imaging method was successful in identifying tissues with sufficiently distinct spectra. (paper)

Stroke mimic diagnoses presenting to a hyperacute stroke unit.

Science.gov (United States)

Dawson, Ang; Cloud, Geoffrey C; Pereira, Anthony C; Moynihan, Barry J

2016-10-01

Stroke services have been centralised in several countries in recent years. Diagnosing acute stroke is challenging and a high proportion of patients admitted to stroke units are diagnosed as a non-stroke condition (stroke mimics). This study aims to describe the stroke mimic patient group, including their impact on stroke services. We analysed routine clinical data from 2,305 consecutive admissions to a stroke unit at St George's Hospital, London. Mimic groupings were derived from 335 individual codes into 17 groupings. From 2,305 admissions, 555 stroke mimic diagnoses were identified (24.2%) and 72% of stroke mimics had at least one stroke risk factor. Common mimic diagnoses were headache, seizure and syncope. Medically unexplained symptoms and decompensation of underlying conditions were also common. Median length of stay was 1 day; a diagnosis of dementia (p=0.028) or needing MRI (p=0.006) was associated with a longer stay. Despite emergency department assessment by specialist clinicians and computed tomography brain, one in four suspected stroke patients admitted to hospital had a non-stroke diagnosis. Stroke mimics represent a heterogeneous patient group with significant impacts on stroke services. Co-location of stroke and acute neurology services may offer advantages where service reorganisation is being considered. © Royal College of Physicians 2016. All rights reserved.

A determination of the CKM-matrix element ratio vertical stroke Vtsvertical stroke /vertical stroke Vcbvertical stroke from the rare B-decays B →K*+γ and B →Xs + γ

International Nuclear Information System (INIS)

Ali, A.; Greub, C.

1993-05-01

Implication of the recent CLEO observation of the rare decay mode B→K * +γhaving a combined branching ratio BR(B→K * +γ)=(4.5±1.5±0.9)x10 -5 and an improved upper limit on the inclusive branching ratio BR(B→X s +γ) -4 (95% C.L.) are discussed in the context of the Standard Model (SM). Unsing the unitarity of the CKM-matrix and taking into account QCD radiative corrections in the decay rate and the inclusive photon energy spectrum we obtain an improved upper limit on the inclusive branching ratio BR(B→X s +γ) -4 (95% C.L.). This can be used to constrain possible non-SM contributions to the inclusive branching ratio, giving BR(B→X s +γ)(non-SM) -4 for m t ≥108 GeV. Within the SM, we show that the resulting experimental upper limit can be interpreted as a corresponding limit on the CKM-matrix element ratio yielding vertical stroke V ts vertical stroke /vertical stroke V cb vertical stroke * /X s )≡Γ(B→K * +γ)/Γ(B→X s +γ), based on the inclusive hadronic invariant mass distribution in B→X s +γ. Estimating the K * -contribution from this distribution in the threshold region (m K +m π)≤ m X s ≤0.97 GeV and using experimental measurements from the semileptonic D-decays D→K+π+lν l in the same mass interval, we obtain R(K * /X s )=0.13±0.03. This enables us to put a lower bound on the ratio vertical stroke V ts vertical stroke /vertical stroke V cb vertical stroke from the 95% C.L. lower limit on the branching rato BR(B→K * +γ)>1.6x10 -5 . Combining the exclusive and inclusive decay rates, we determine 0.50≤vertical stroke V ts vertical stroke /vertical stroke V cb vertical stroke ≤1.67 (at 95% C.L.). (orig.). 7 figs

Sex Differences in Stroke Survival: 10-Year Follow-up of the Copenhagen Stroke Study Cohort

DEFF Research Database (Denmark)

Andersen, Morten Nonboe; Andersen, Klaus Kaae; Kammersgaard, Lars Peter

2005-01-01

BACKGROUND: Although diverging, most studies show that sex has no significant influence on stroke survival. METHODS: In a Copenhagen, Denmark, community all patients with stroke during March 1992 to November 1993 were registered on hospital admission. Stroke severity was measured using the Scandi......BACKGROUND: Although diverging, most studies show that sex has no significant influence on stroke survival. METHODS: In a Copenhagen, Denmark, community all patients with stroke during March 1992 to November 1993 were registered on hospital admission. Stroke severity was measured using......-up period. Predictors of death were identified using a Cox proportional hazards model. RESULTS: Of 999 patients, 559 (56%) were women and 440 (44%) were men. Women were older (77.0 v 70.9 years; P ... factors showed no difference between sexes for ischemic heart disease, hypertension, atrial fibrillation, diabetes mellitus, and previous stroke. Men more often were smokers and alcohol consumers. Unadjusted survival in men and women did not differ: 70.3% versus 66.7% (1-year), 40.0% versus 38.9% (5-year...

Sex differences in stroke survival: 10-year follow-up of the Copenhagen stroke study cohort

DEFF Research Database (Denmark)

Andersen, Morten Nonboe; Andersen, Klaus Kaae; Kammersgaard, Lars Peter

2005-01-01

BACKGROUND: Although diverging, most studies show that sex has no significant influence on stroke survival. METHODS: In a Copenhagen, Denmark, community all patients with stroke during March 1992 to November 1993 were registered on hospital admission. Stroke severity was measured using the Scandi......BACKGROUND: Although diverging, most studies show that sex has no significant influence on stroke survival. METHODS: In a Copenhagen, Denmark, community all patients with stroke during March 1992 to November 1993 were registered on hospital admission. Stroke severity was measured using......-up period. Predictors of death were identified using a Cox proportional hazards model. RESULTS: Of 999 patients, 559 (56%) were women and 440 (44%) were men. Women were older (77.0 v 70.9 years; P ... factors showed no difference between sexes for ischemic heart disease, hypertension, atrial fibrillation, diabetes mellitus, and previous stroke. Men more often were smokers and alcohol consumers. Unadjusted survival in men and women did not differ: 70.3% versus 66.7% (1-year), 40.0% versus 38.9% (5-year...

Heritability of young- and old-onset ischaemic stroke.

Science.gov (United States)

Bluher, A; Devan, W J; Holliday, E G; Nalls, M; Parolo, S; Bione, S; Giese, A K; Boncoraglio, G B; Maguire, J M; Müller-Nurasyid, M; Gieger, C; Meschia, J F; Rosand, J; Rolfs, A; Kittner, S J; Mitchell, B D; O'Connell, J R; Cheng, Y C

2015-11-01

Although the genetic contribution to stroke risk is well known, it remains unclear if young-onset stroke has a stronger genetic contribution than old-onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole-genome array data in population-based samples. This analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young-onset stroke (age stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole-genome array data using a mixed linear model. Heritability was estimated separately for young-onset stroke and old-onset stroke (age ≥ 55 years). Heritabilities for young-onset stroke and old-onset stroke were estimated at 42% (±8%, P genetic contribution to the risk of stroke may be higher in young-onset ischaemic stroke, although the difference was not statistically significant. © 2015 EAN.

Cyclosporin A-Mediated Activation of Endogenous Neural Precursor Cells Promotes Cognitive Recovery in a Mouse Model of Stroke

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Labeeba Nusrat

2018-04-01

Full Text Available Cognitive dysfunction following stroke significantly impacts quality of life and functional independance; yet, despite the prevalence and negative impact of cognitive deficits, post-stroke interventions almost exclusively target motor impairments. As a result, current treatment options are limited in their ability to promote post-stroke cognitive recovery. Cyclosporin A (CsA has been previously shown to improve post-stroke functional recovery of sensorimotor deficits. Interestingly, CsA is a commonly used immunosuppressant and also acts directly on endogenous neural precursor cells (NPCs in the neurogenic regions of the brain (the periventricular region and the dentate gyrus. The immunosuppressive and NPC activation effects are mediated by calcineurin-dependent and calcineurin-independent pathways, respectively. To develop a cognitive stroke model, focal bilateral lesions were induced in the medial prefrontal cortex (mPFC of adult mice using endothelin-1. First, we characterized this stroke model in the acute and chronic phase, using problem-solving and memory-based cognitive tests. mPFC stroke resulted in early and persistent deficits in short-term memory, problem-solving and behavioral flexibility, without affecting anxiety. Second, we investigated the effects of acute and chronic CsA treatment on NPC activation, neuroprotection, and tissue damage. Acute CsA administration post-stroke increased the size of the NPC pool. There was no effect on neurodegeneration or lesion volume. Lastly, we looked at the effects of chronic CsA treatment on cognitive recovery. Long-term CsA administration promoted NPC migration toward the lesion site and rescued cognitive deficits to control levels. This study demonstrates that CsA treatment activates the NPC population, promotes migration of NPCs to the site of injury, and leads to improved cognitive recovery following long-term treatment.

Animal Models Used to Explore Abdominal Aortic Aneurysms

DEFF Research Database (Denmark)

Lysgaard Poulsen, J; Stubbe, J; Lindholt, J S

2016-01-01

OBJECTIVE: Experimental animal models have been used to investigate the formation, development, and progression of abdominal aortic aneurysms (AAAs) for decades. New models are constantly being developed to imitate the mechanisms of human AAAs and to identify treatments that are less risky than...... those used today. However, to the authors' knowledge, there is no model identical to the human AAA. The objective of this systematic review was to assess the different types of animal models used to investigate the development, progression, and treatment of AAA and to highlight their advantages...... and limitations. METHODS: A search protocol was used to perform a systematic literature search of PubMed and Embase. A total of 2,830 records were identified. After selection of the relevant articles, 564 papers on animal AAA models were included. RESULTS: The most common models in rodents, including elastase...

Temporal trends in hospitalisation for stroke recurrence following incident hospitalisation for stroke in Scotland

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Langhorne Peter

2010-04-01

Full Text Available Abstract Background There are few studies that have investigated temporal trends in risk of recurrent stroke. The aim of this study was to examine temporal trends in hospitalisation for stroke recurrence following incident hospitalisation for stroke in Scotland during 1986 to 2001. Methods Unadjusted survival analysis of time to first event, hospitalisation for recurrent stroke or death, was undertaken using the cumulative incidence method which takes into account competing risks. Regression on cumulative incidence functions was used to model the temporal trends of first recurrent stroke with adjustment for age, sex, socioeconomic status and comorbidity. Complete five year follow-up was obtained for all patients. Restricted cubic splines were used to determine the best fitting relationship between the survival events and study year. Results There were 128,511 incident hospitalisations for stroke in Scotland between 1986 and 2001, 57,351 (45% in men. A total of 13,835 (10.8% patients had a recurrent hospitalisation for stroke within five years of their incident hospitalisation. Another 74,220 (57.8% patients died within five years of their incident hospitalisation without first having a recurrent hospitalisation for stroke. Comparing incident stroke hospitalisations in 2001 with 1986, the adjusted risk of recurrent stroke hospitalisation decreased by 27%, HR = 0.73 95% CI (0.67 to 0.78, and the adjusted risk of death being the first event decreased by 28%, HR = 0.72 (0.70 to 0.75. Conclusions Over the 15-year period approximately 1 in 10 patients with an incident hospitalisation for stroke in Scotland went on to have a hospitalisation for recurrent stroke within five years. Approximately 6 in 10 patients died within five years without first having a recurrent stroke hospitalisation. Using hospitalisation and death data from an entire country over a 20-year period we have been able to demonstrate not only an improvement in survival following an

The role of angiogenesis in damage and recovery from ischemic stroke.

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Arenillas, Juan F; Sobrino, Tomás; Castillo, José; Dávalos, Antoni

2007-06-01

Ischemic stroke is burdened with a high morbidity and mortality in our society. However, there are few effective and largely available therapies for this devastating disease. In additon to advancing acute reperfusion therapies, there is a need to develop treatments aimed to promote repair and regeneration of brain tissue damaged by ischemia (neurorecovery). Therapeutic angiogenesis and vasculogenesis represent novel approaches of regenerative medicine that may help in the cure of patients with acute ischemic stroke. Translation of our knowledge about these processes from the bench to bedside is still underway. Although angiogenesis (the sprouting of new blood vessels from pre-existing vascular structures) is likely to contribute to neurorepair, the finality of the angiogenic response in acute ischemic stroke has not been fully elucidated. The first therapeutic approach to angiogenesis after ischemic stroke would be the modulation of the endogenous angiogenic response. In this setting, early instauration of physical activity, statins, and peroxisome proliferator-activated receptor-gamma agonists may enhance angiogenesis and neuroregeneration. Gene therapy with vascular growth factors has been successfully tested in patients affected by chronic myocardial and peripheral ischemia. Regarding brain ischemia, experiments in animal models have shown that the effect of these growth factors is critically affected by the dosage, route of delivery, and time of administration in relation to stroke onset. In addition, the optimal angiogenic substance is unknown. Finally, vectors for gene transfer should be further optimized. Therapeutic vasculogenesis consists of the administration of exogenous endothelial progenitor cells in order to enhance brain repair processes. Endothelial progenitor cells may be recruited in response to cerebral ischemia and participate in reparative vasculogenesis after acute ischemic stroke. Further research is needed to clarify their role and

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models.

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Uno, Narumi; Abe, Satoshi; Oshimura, Mitsuo; Kazuki, Yasuhiro

2018-02-01

Chromosome transfer technology, including chromosome modification, enables the introduction of Mb-sized or multiple genes to desired cells or animals. This technology has allowed innovative developments to be made for models of human disease and humanized animals, including Down syndrome model mice and humanized transchromosomic (Tc) immunoglobulin mice. Genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell lines and animals. This review summarizes chromosome transfer-related technologies and the combined technologies of chromosome transfer and genome editing mainly for the production of cell/animal models of human disease and humanized animal models. Specifically, these include: (1) chromosome modification with genome editing in Chinese hamster ovary cells and mouse A9 cells for efficient transfer to desired cell types; (2) single-nucleotide polymorphism modification in humanized Tc mice with genome editing; and (3) generation of a disease model of Down syndrome-associated hematopoiesis abnormalities by the transfer of human chromosome 21 to normal human embryonic stem cells and the induction of mutation(s) in the endogenous gene(s) with genome editing. These combinations of chromosome transfer and genome editing open up new avenues for drug development and therapy as well as for basic research.

Optical scatter imaging of cellular and mitochondrial swelling in brain tissue models of stroke

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Johnson, Lee James

2001-08-01

The severity of brain edema resulting from a stroke can determine a patient's survival and the extent of their recovery. Cellular swelling is the microscopic source of a significant part of brain edema. Mitochondrial swelling also appears to be a determining event in the death or survival of the cells that are injured during a stroke. Therapies for reducing brain edema are not effective in many cases and current treatments of stroke do not address mitochondrial swelling at all. This dissertation is motivated by the lack of a complete understanding of cellular swelling resulting from stroke and the lack of a good method to begin to study mitochondrial swelling resulting from stroke in living brain tissue. In this dissertation, a novel method of detecting mitochondrial and cellular swelling in living hippocampal slices is developed and validated. The system is used to obtain spatial and temporal information about cellular and mitochondrial swelling resulting from various models of stroke. The effect of changes in water content on light scatter and absorption are examined in two models of brain edema. The results of this study demonstrate that optical techniques can be used to detect changes in water content. Mie scatter theory, the theoretical basis of the dual- angle scatter ratio imaging system, is presented. Computer simulations based on Mie scatter theory are used to determine the optimal angles for imaging. A detailed account of the early systems is presented to explain the motivations for the system design, especially polarization, wavelength and light path. Mitochondrial sized latex particles are used to determine the system response to changes in scattering particle size and concentration. The dual-angle scatter ratio imaging system is used to distinguish between osmotic and excitotoxic models of stroke injury. Such distinction cannot be achieved using the current techniques to study cellular swelling in hippocampal slices. The change in the scatter ratio is

Laboratory animal models for esophageal cancer

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Dhanya Venugopalan Nair

2016-11-01

Full Text Available The incidence of esophageal cancer is rapidly increasing especially in developing countries. The major risk factors include unhealthy lifestyle practices such as alcohol consumption, smoking, and chewing tobacco to name a few. Diagnosis at an advanced stage and poor prognosis make esophageal cancer one of the most lethal diseases. These factors have urged further research in understanding the pathophysiology of the disease. Animal models not only aid in understanding the molecular pathogenesis of esophageal cancer but also help in developing therapeutic interventions for the disease. This review throws light on the various recent laboratory animal models for esophageal cancer.

Reproducibility of preclinical animal research improves with heterogeneity of study samples

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Vogt, Lucile; Sena, Emily S.; Würbel, Hanno

2018-01-01

Single-laboratory studies conducted under highly standardized conditions are the gold standard in preclinical animal research. Using simulations based on 440 preclinical studies across 13 different interventions in animal models of stroke, myocardial infarction, and breast cancer, we compared the accuracy of effect size estimates between single-laboratory and multi-laboratory study designs. Single-laboratory studies generally failed to predict effect size accurately, and larger sample sizes rendered effect size estimates even less accurate. By contrast, multi-laboratory designs including as few as 2 to 4 laboratories increased coverage probability by up to 42 percentage points without a need for larger sample sizes. These findings demonstrate that within-study standardization is a major cause of poor reproducibility. More representative study samples are required to improve the external validity and reproducibility of preclinical animal research and to prevent wasting animals and resources for inconclusive research. PMID:29470495

Animal Models of Allergic Diseases

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Domenico Santoro

2014-12-01

Full Text Available Allergic diseases have great impact on the quality of life of both people and domestic animals. They are increasing in prevalence in both animals and humans, possibly due to the changed lifestyle conditions and the decreased exposure to beneficial microorganisms. Dogs, in particular, suffer from environmental skin allergies and develop a clinical presentation which is very similar to the one of children with eczema. Thus, dogs are a very useful species to improve our understanding on the mechanisms involved in people’s allergies and a natural model to study eczema. Animal models are frequently used to elucidate mechanisms of disease and to control for confounding factors which are present in studies with patients with spontaneously occurring disease and to test new therapies that can be beneficial in both species. It has been found that drugs useful in one species can also have benefits in other species highlighting the importance of a comprehensive understanding of diseases across species and the value of comparative studies. The purpose of the current article is to review allergic diseases across species and to focus on how these diseases compare to the counterpart in people.

Animal Models of Diabetic Retinopathy: Summary and Comparison

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Lo, Amy C. Y.

2013-01-01

Diabetic retinopathy (DR) is a microvascular complication associated with chronic exposure to hyperglycemia and is a major cause of blindness worldwide. Although clinical assessment and retinal autopsy of diabetic patients provide information on the features and progression of DR, its underlying pathophysiological mechanism cannot be deduced. In order to have a better understanding of the development of DR at the molecular and cellular levels, a variety of animal models have been developed. They include pharmacological induction of hyperglycemia and spontaneous diabetic rodents as well as models of angiogenesis without diabetes (to compensate for the absence of proliferative DR symptoms). In this review, we summarize the existing protocols to induce diabetes using STZ. We also describe and compare the pathological presentations, in both morphological and functional aspects, of the currently available DR animal models. The advantages and disadvantages of using different animals, ranging from zebrafish, rodents to other higher-order mammals, are also discussed. Until now, there is no single model that displays all the clinical features of DR as seen in human. Yet, with the understanding of the pathological findings in these animal models, researchers can select the most suitable models for mechanistic studies or drug screening. PMID:24286086

Neuroprotection of Catalpol for Experimental Acute Focal Ischemic Stroke: Preclinical Evidence and Possible Mechanisms of Antioxidation, Anti-Inflammation, and Antiapoptosis

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Xia-wei Zheng

2017-01-01

Full Text Available Neuroprotection is defined as using a therapy that affects the brain tissue in the still-viable ischemic penumbra to salvage or delay the infarction. Catalpol, the main active principle of the root of Radix Rehmanniae, was reported to have pleiotropic neuroprotective effects in neurodegenerative diseases including ischemic stroke. Here, we evaluated the neuroprotective effects of catalpol in experimental acute ischemic stroke. Studies on catalpol in animal models of acute ischemic stroke were identified from 6 databases. Twenty-five studies involving 805 animals were included. Twelve comparisons showed significant effects of catalpol on decreasing infarct size according to 2,3,5-triphenyltetrazolium chloride staining compared with the control (P<0.05. One study reported significant effect of catalpol on reducing infarct size according to magnetic resonance imaging scan compared with the control (P<0.05. Meta-analysis of these studies indicated that catalpol significantly improved the neurological function score according to Zea Longa score, Bederson score, balance beam-walking test, adhesive removal test, bar-grasping score, and corner test compared with the control (P<0.05. In conclusion, catalpol exerted neuroprotective effects for experimental acute focal ischemic stroke, largely through reducing oxidative reactions, inhibiting apoptosis, and repressing inflammatory reactions and autophagy. However, these apparently positive findings should be interpreted with caution because of the methodological flaws.

Improving Community Stroke Preparedness in the HHS (Hip-Hop Stroke) Randomized Clinical Trial.

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Williams, Olajide; Leighton-Herrmann Quinn, Ellyn; Teresi, Jeanne; Eimicke, Joseph P; Kong, Jian; Ogedegbe, Gbenga; Noble, James

2018-04-01

Deficiencies in stroke preparedness cause major delays to stroke thrombolysis, particularly among economically disadvantaged minorities. We evaluated the effectiveness of a stroke preparedness intervention delivered to preadolescent urban public school children on the stroke knowledge/preparedness of their parents. We recruited 3070 fourth through sixth graders and 1144 parents from 22 schools into a cluster randomized trial with schools randomized to the HHS (Hip-Hop Stroke) intervention or attentional control (nutrition classes). HHS is a 3-hour culturally tailored, theory-based, multimedia stroke literacy intervention targeting school children, which systematically empowers children to share stroke information with parents. Our main outcome measures were stroke knowledge/preparedness of children and parents using validated surrogates. Among children, it was estimated that 1% (95% confidence interval [CI], 0%-1%) of controls and 2% (95% CI, 1%-4%; P =0.09) of the intervention group demonstrated optimal stroke preparedness (perfect scores on the knowledge/preparedness test) at baseline, increasing to 57% (95% CI, 44%-69%) immediately after the program in the intervention group compared with 1% (95% CI, 0%-1%; P <0.001) among controls. At 3-month follow-up, 24% (95% CI, 15%-33%) of the intervention group retained optimal preparedness, compared with 2% (95% CI, 0%-3%; P <0.001) of controls. Only 3% (95% CI, 2%-4%) of parents in the intervention group could identify all 4 letters of the stroke FAST (Facial droop, Arm weakness, Speech disturbance, Time to call 911) acronym at baseline, increasing to 20% at immediate post-test (95% CI, 16%-24%) and 17% at 3-month delayed post-test (95% CI, 13%-21%; P =0.0062), with no significant changes (3% identification) among controls. Four children, all in the intervention group, called 911 for real-life stroke symptoms, in 1 case overruling a parent's wait-and-see approach. HHS is an effective, intergenerational model for

Possible Anandamide and Palmitoylethanolamide involvement in human stroke

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Pizzolato Gilberto

2010-05-01

Full Text Available Abstract Background Endocannabinoids (eCBs are ubiquitous lipid mediators that act on specific (CB1, CB2 and non-specific (TRPV1, PPAR receptors. Despite many experimental animal studies proved eCB involvement in the pathogenesis of stroke, such evidence is still lacking in human patients. Our aim was to determine eCB peripheral levels in acute stroke patients and evaluate their relationship with clinical disability and stroke volume. Methods A cohort of ten patients with a first acute (within six hours since symptoms onset ischemic stroke and a group of eight age- and sex-matched normal subjects were included. Groups were also matched for metabolic profile. All subjects underwent a blood sample collection for anandamide (AEA, 2-arachidonoylglycerol (2-AG and palmitoylethanolamide (PEA measurement; blood sampling was repeated in patients on admission (T0, at 6 (T1 and 18 hours (T2 thereafter. Patients neurological impairment was assessed using NIHSS and Fugl-Meyer Scale arm subitem (FMSa; stroke volume was determined on 48 h follow-up brain CT scans. Blood samples were analyzed by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. Results 1T0 AEA levels were significantly higher in stroke patients compared to controls. 2A significant inverse correlation between T0 AEA levels and FMSa score was found. Moreover a positive correlation between T0 AEA levels and stroke volume were found in stroke patients. T0 PEA levels in stroke patients were not significantly different from the control group, but showed a significant correlation with the NIHSS scores. T0 2-AG levels were lower in stroke patients compared to controls, but such difference did not reach the significance threshold. Conclusions This is the first demonstration of elevated peripheral AEA levels in acute stroke patients. In agreement with previous murine studies, we found a significant relationship between AEA or PEA levels and neurological involvement, such

Stem cell therapies in preclinical models of stroke. Is the aged brain microenvironment refractory to cell therapy?

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Sandu, Raluca Elena; Balseanu, Adrian Tudor; Bogdan, Catalin; Slevin, Mark; Petcu, Eugen; Popa-Wagner, Aurel

2017-08-01

Stroke is a devastating disease demanding vigorous search for new therapies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizing impediments that may be related to unfavorable age-associated environments. Recent results using a variety of drug, cell therapy or combination thereof suggest that, (i) treatment with Granulocyte-Colony Stimulating Factor (G-CSF) in aged rats has primarily a beneficial effect on functional outcome most likely via supportive cellular processes such as neurogenesis; (ii) the combination therapy, G-CSF with mesenchymal cells (G-CSF+BM-MSC or G-CSF+BM-MNC) did not further improve behavioral indices, neurogenesis or infarct volume as compared to G-CSF alone in aged animals; (iii) better results with regard to integration of transplanted cells in the aged rat environment have been obtained using iPS of human origin; (iv) mesenchymal cells may be used as drug carriers for the aged post-stroke brains. While the middle aged brain does not seem to impair drug and cell therapies, in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time. Copyright © 2017. Published by Elsevier Inc.

[The effect of nitrates on the outcome of acute experimental ischemic stroke].

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Kuzenkov, V S; Krushinskiĭ, A L; Reutov, V P

2012-01-01

Effects of nitrates NaNO(3), KNO(3), Mg(NO(3)) 2 on animals (Wistar rats) were studied on the basis of the experimental model of ischemic stroke induced by the occlusion of two carotid arteries. The animals were divided into two groups: the main group (n=60) and the control group (n=30). Three series of experiments were conducted. In each experiment, the rats of the main group were treated with one of nitrates and the control group was treated with physiological solution. It has been shown that nitrates exert either positive or negative effect depending on the cation type, nitrate concentration and the duration of their action on the dynamics of neurologic disturbances. Conditions of the development of neuroprotective effect of nitrates are discussed.

Enriched environment reduces apolipoprotein E (ApoE) in reactive astrocytes and attenuates inflammation of the peri-infarct tissue after experimental stroke

DEFF Research Database (Denmark)

Ruscher, Karsten; Johannesson, Emelie; Brugiere, Elena

2009-01-01

Apolipoprotein E (ApoE), a cholesterol transporter and an immunomodulator, is brain protective after experimental stroke and implicated in brain repair. Here, we study the involvement of ApoE in the restoration of brain function after experimental stroke, by using animal housing conditions...... lower in animals housed in an enriched environment. We propose that during the subacute phase after experimental stroke a zone for tissue reorganization with low cellular ApoE levels is formed. We conclude that the strong sensori-motor stimulation provided by enriched housing conditions mitigates...

Contemporary Animal Models For Human Gene Therapy Applications.

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Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Nelson, Everette Jacob Remington

2015-01-01

Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.

Exploring the Experiences of Living With Stroke Through Narrative: Stroke Survivors' Perspectives.

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Nasr, Nasrin; Mawson, Susan; Wright, Peter; Parker, Jack; Mountain, Gail

2016-01-01

Chronic illness models are normally used to explain and predict the experience of living with a long-term condition. The aim of this study was to present the findings of narrative interviews with stroke survivors and their family carers to understand their experiences of stroke. We interviewed five people with stroke and three family carers from the United Kingdom. We used thematic analysis to generate themes from their narrative accounts and then linked them to broader theoretical perspectives while influenced by the concept of reinterpretation of life. The narrative accounts of participants are mainly structured based on how their changed bodies poststroke changed their identities and roles and consequently their relationships with others. In this study, we underline the need for using methods like narrative to explain strategies that people use to make sense of their experiences of living with a long-term condition such as stroke.

Day/night difference in extradural cortical stimulation for motor relearning in a subacute stroke rat model.

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Kim, Joo Yeon; Sun, Woong; Park, Eunhee; Lee, Jiyeong; Kim, Hyun; Shin, Yong-Il; Kim, Yun-Hee; Chang, Won Hyuk

2016-02-24

The aim of this study was to assess the proper timing of extradural cortical stimulation (ECS) on the motor relearning in a rat model of subacute photothrombotic stroke. Photothrombotic infarction was induced on the dominant sensorimotor cortex in male Sprague-Dawley rats after training in a single-pellet reaching task (SPRT). Rats were randomly divided into three groups after stroke: ECS during the inactive period (Day-ECS group), ECS during the active period (Night-ECS group) and no ECS (Non-stimulated group). Six sham-operated rats were assigned to the control group. The Day- and Night-ECS group received continuous ECS for 12 hours during the day or night for 2 weeks from day 4 after the stroke. Behavioral assessment with SPRT was performed daily. SPRT showed a significantly faster and greater improvement in the Day and Night-ECS groups than in the Non-stimulated group. In the Day- and Night-ECS groups, the success rate of SPRT differed significantly from Non-stimulated group on day 11 and day 8, respectively. In addition, the Night-ECS group showed a significantly higher SPRT success rate than the Day-ECS group from days 10 to 13. ECS during the active period might be more effective for motor relearning in the subacute stroke rat model.

The complete guide to blender graphics computer modeling and animation

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Blain, John M

2014-01-01

Smoothly Leads Users into the Subject of Computer Graphics through the Blender GUIBlender, the free and open source 3D computer modeling and animation program, allows users to create and animate models and figures in scenes, compile feature movies, and interact with the models and create video games. Reflecting the latest version of Blender, The Complete Guide to Blender Graphics: Computer Modeling & Animation, 2nd Edition helps beginners learn the basics of computer animation using this versatile graphics program. This edition incorporates many new features of Blender, including developments

Sex-related time-dependent variations in post-stroke survival-evidence of a female stroke survival advantage

DEFF Research Database (Denmark)

Olsen, Tom Skyhøj; Dehlendorff, Christian; Andersen, Klaus Kaae

2007-01-01

the influence of gender on post-stroke mortality, from the time of admission through the subsequent years until death or censoring ( mean follow-up time: 538 days). All patients underwent an evaluation including stroke severity, computed tomography and cardiovascular risk factors. Independent predictors......Background: Women live longer than men, yet most studies show that gender has no influence on survival after stroke. Methods: A registry was started in 2001, with the aim of registering all hospitalized stroke patients in Denmark, and it now holds 39,484 patients of which 48% are female. We studied...... of death were identified by means of a survival model based on 22,222 individuals with a complete data set. Results: Females were older and had severer stroke. Interestingly, the risk of death between genders was time dependent. The female/male stroke mortality rate favoured women from the first day...

Determinations of vertical stroke V{sub cb} vertical stroke and vertical stroke V{sub ub} vertical stroke from baryonic Λ{sub b} decays

Energy Technology Data Exchange (ETDEWEB)

Hsiao, Y.K. [Shanxi Normal University, School of Physics and Information Engineering, Linfen (China); National Tsing Hua University, Department of Physics, Hsinchu (China); Geng, C.Q. [Shanxi Normal University, School of Physics and Information Engineering, Linfen (China); National Tsing Hua University, Department of Physics, Hsinchu (China); Hunan Normal University, Synergetic Innovation Center for Quantum Effects and Applications (SICQEA), Changsha (China)

2017-10-15

We present the first attempt to extract vertical stroke V{sub cb} vertical stroke from the Λ{sub b} → Λ{sub c}{sup +}l anti ν{sub l} decay without relying on vertical stroke V{sub ub} vertical stroke inputs from the B meson decays. Meanwhile, the hadronic Λ{sub b} → Λ{sub c}M{sub (c)} decays with M = (π{sup -},K{sup -}) and M{sub c} =(D{sup -},D{sup -}{sub s}) measured with high precisions are involved in the extraction. Explicitly, we find that vertical stroke V{sub cb} vertical stroke =(44.6 ± 3.2) x 10{sup -3}, agreeing with the value of (42.11 ± 0.74) x 10{sup -3} from the inclusive B → X{sub c}l anti ν{sub l} decays. Furthermore, based on the most recent ratio of vertical stroke V{sub ub} vertical stroke / vertical stroke V{sub cb} vertical stroke from the exclusive modes, we obtain vertical stroke V{sub ub} vertical stroke = (4.3 ± 0.4) x 10{sup -3}, which is close to the value of (4.49 ± 0.24) x 10{sup -3} from the inclusive B → X{sub u}l anti ν{sub l} decays. We conclude that our determinations of vertical stroke V{sub cb} vertical stroke and vertical stroke V{sub ub} vertical stroke favor the corresponding inclusive extractions in the B decays. (orig.)

Animal models of GM2 gangliosidosis: utility and limitations

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Lawson, Cheryl A; Martin, Douglas R

2016-01-01

GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

[Relationship between weather factors and heat stroke in Ningbo city].

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Gu, S H; Wang, A H; Bian, G L; He, T F; Yi, B; Lu, B B; Li, X H; Xu, G Z

2016-08-10

To explore the main effects of weather factors on heat stroke. Data from case report on heat stroke was collected in Ningbo city during 2011 to 2014. Temperature threshold, lag effects and interaction of weather factors on heat stroke had been analyzed, using the piecewise regression model, distributed lag non-linear model, response surface model and other methods. RESULTS showed that temperature and humidity were more correlated with heat stroke than other weather-related factors. Through different models, daily average temperature always presented a better role in predicting the heat stroke, rather than maximum or minimum temperature. Positive association between daily average temperature and heat stroke was obvious, especially at lag 0-1 days, with its threshold as 29.1 (95% CI: 28.7-29.5) ℃ . The cumulative RR of heat stroke at 90(th) percentile of daily average temperature versus 10(th) percentile was 14.05 (95% CI: 7.23-27.31) in lag 0-1 days. The effects of daily relative humidity on heat stroke appeared nonlinear, with low humidity showing a negative effect on heat stroke and could lag for 1-4 days. However, the effect of high humidity was not significant, with the cumulative RR of low humidity and high humidity as 2.35 (95%CI: 1.27-4.33) and 0.86 (95%CI: 0.40-1.85) in lag of 0-4 days, respectively. We also noticed that there was an interactive effect of both temperature and humidity on heat stroke. Under high temperature and low humidity, the risk of heat stroke showed the highest. Temperature and humidity showed obvious relationship with heat stroke in Ningbo city, with the threshold temperature as 29.1 ℃. Under high temperature and low humidity, the risk of heat stroke became the highest.

Cryptogenic Stroke

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Mohammad Saadatnia

2017-02-01

Full Text Available Cryptogenic stroke is defined as brain infarction that is not attributable to a source of definite embolism, large artery atherosclerosis, or small artery disease despite a thorough vascular, cardiac, and serologic evaluation. Despite many advances in our understanding of ischemic stroke, cryptogenic strokes remain a diagnostic and therapeutic challenge. The pathophysiology of cryptogenic stroke is likely various. Probable mechanisms include cardiac embolism secondary to occult paroxysmal atrial fibrillation, aortic atheromatous disease or other cardiac sources, paradoxical embolism from atrial septal abnormalities such as patent foramen ovale, hypercoagulable states, and preclinical or subclinical cerebrovascular disease.  Cryptogenic stroke is one-fourth among cerebral infarction, but most of them could be ascribed to embolic stroke. A significant proportion of cryptogenic strokes adhere to embolic infarct topography on brain imaging and improvement in our ability to detect paroxysmal atrial fibrillation in patients with cryptogenic stroke has strengthened the idea that these strokes are embolic in nature. a significant proportion of cryptogenic strokes adhere to embolic infarct topography on brain imaging.embolic stroke of undetermined sources(ESUS was planned for unifying embolic stroke of undetermined source.  The etiologies underlying ESUS included minor-risk potential cardioembolic sources, covert paroxysmal atrial fibrillation, cancer-associated coagulopathy and embolism, arteriogenic emboli, and paroxysmal embolism. Extensive evaluation including transesophageal echocardiography and cardiac monitoring for long time could identify the etiology of these patients. Therefore cryptogenic stroke is a diagnosis of exclusion. Compared with other stroke subtypes, cryptogenic stroke tends to have a better prognosis and lower long-term risk of recurrence.

Animal models of chronic obstructive pulmonary disease.

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Pérez-Rial, Sandra; Girón-Martínez, Álvaro; Peces-Barba, Germán

2015-03-01

Animal models of disease have always been welcomed by the scientific community because they provide an approach to the investigation of certain aspects of the disease in question. Animal models of COPD cannot reproduce the heterogeneity of the disease and usually only manage to represent the disease in its milder stages. Moreover, airflow obstruction, the variable that determines patient diagnosis, not always taken into account in the models. For this reason, models have focused on the development of emphysema, easily detectable by lung morphometry, and have disregarded other components of the disease, such as airway injury or associated vascular changes. Continuous, long-term exposure to cigarette smoke is considered the main risk factor for this disease, justifying the fact that the cigarette smoke exposure model is the most widely used. Some variations on this basic model, related to exposure time, the association of other inducers or inhibitors, exacerbations or the use of transgenic animals to facilitate the identification of pathogenic pathways have been developed. Some variations or heterogeneity of this disease, then, can be reproduced and models can be designed for resolving researchers' questions on disease identification or treatment responses. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Imaging of Small Animal Peripheral Artery Disease Models: Recent Advancements and Translational Potential

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Jenny B. Lin

2015-05-01

Full Text Available Peripheral artery disease (PAD is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular information and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic.

Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient.

Science.gov (United States)

Datta, Abhishek; Baker, Julie M; Bikson, Marom; Fridriksson, Julius

2011-07-01

Although numerous published reports have demonstrated the beneficial effects of transcranial direct-current stimulation (tDCS) on task performance, fundamental questions remain regarding the optimal electrode configuration on the scalp. Moreover, it is expected that lesioned brain tissue will influence current flow and should therefore be considered (and perhaps leveraged) in the design of individualized tDCS therapies for stroke. The current report demonstrates how different electrode configurations influence the flow of electrical current through brain tissue in a patient who responded positively to a tDCS treatment targeting aphasia. The patient, a 60-year-old man, sustained a left hemisphere ischemic stroke (lesion size = 87.42 mL) 64 months before his participation. In this study, we present results from the first high-resolution (1 mm(3)) model of tDCS in a brain with considerable stroke-related damage; the model was individualized for the patient who received anodal tDCS to his left frontal cortex with the reference cathode electrode placed on his right shoulder. We modeled the resulting brain current flow and also considered three additional reference electrode positions: right mastoid, right orbitofrontal cortex, and a "mirror" configuration with the anode over the undamaged right cortex. Our results demonstrate the profound effect of lesioned tissue on resulting current flow and the ability to modulate current pattern through the brain, including perilesional regions, through electrode montage design. The complexity of brain current flow modulation by detailed normal and pathologic anatomy suggest: (1) That computational models are critical for the rational interpretation and design of individualized tDCS stroke-therapy; and (2) These models must accurately reproduce head anatomy as shown here. Copyright © 2011 Elsevier Inc. All rights reserved.

Late night activity regarding stroke codes: LuNAR strokes.

Science.gov (United States)

Tafreshi, Gilda; Raman, Rema; Ernstrom, Karin; Rapp, Karen; Meyer, Brett C

2012-08-01

There is diurnal variation for cardiac arrest and sudden cardiac death. Stroke may show a similar pattern. We assessed whether strokes presenting during a particular time of day or night are more likely of vascular etiology. To compare emergency department stroke codes arriving between 22:00 and 8:00 hours (LuNAR strokes) vs. others (n-LuNAR strokes). The purpose was to determine if late night strokes are more likely to be true strokes or warrant acute tissue plasminogen activator evaluations. We reviewed prospectively collected cases in the University of California, San Diego Stroke Team database gathered over a four-year period. Stroke codes at six emergency departments were classified based on arrival time. Those arriving between 22:00 and 8:00 hours were classified as LuNAR stroke codes, the remainder were classified as 'n-LuNAR'. Patients were further classified as intracerebral hemorrhage, acute ischemic stroke not receiving tissue plasminogen activator, acute ischemic stroke receiving tissue plasminogen activator, transient ischemic attack, and nonstroke. Categorical outcomes were compared using Fisher's Exact test. Continuous outcomes were compared using Wilcoxon's Rank-sum test. A total of 1607 patients were included in our study, of which, 299 (19%) were LuNAR code strokes. The overall median NIHSS was five, higher in the LuNAR group (n-LuNAR 5, LuNAR 7; P=0·022). There was no overall differences in patient diagnoses between LuNAR and n-LuNAR strokes (P=0·169) or diagnosis of acute ischemic stroke receiving tissue plasminogen activator (n-LuNAR 191 (14·6%), LuNAR 42 (14·0%); P=0·86). Mean arrival to computed tomography scan time was longer during LuNAR hours (n-LuNAR 54·9±76·3 min, LuNAR 62·5±87·7 min; P=0·027). There was no significant difference in 90-day mortality (n-LuNAR 15·0%, LuNAR 13·2%; P=0·45). Our stroke center experience showed no difference in diagnosis of acute ischemic stroke between day and night stroke codes. This

Lightning Return Stroke Current Analysis Using Electromagnetic Models and the 3D-FDTD Method

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Kaddour Arzag

2017-03-01

Full Text Available The three dimensions finite difference time domain method (3D-FDTD is employed to calculate lightning return stoke current distributions in a vertical lightning channel. The latter is excited at its bottom by a lumped current source above a flat perfectly conducting ground. In this study four lightning return stroke electromagnetic models are used. The calculating approach, which is based on Taflove formulation of the 3D-FDTD method combined to the UPML boundary conditions, is implemented on Matlab environment. For validation needs, the obtained lightning return stroke space and time distributions are compared with others taken from specialized literature.

Aphasia As a Predictor of Stroke Outcome.

Science.gov (United States)

Lazar, Ronald M; Boehme, Amelia K

2017-09-19

Aphasia is a common feature of stroke, affecting 21-38% of acute stroke patients and an estimated 1 million stroke survivors. Although stroke, as a syndrome, is the leading cause of disability in the USA, less is known about the independent impact of aphasia on stroke outcomes. During the acute stroke period, aphasia has been found to increase length of stay, inpatient complications, overall neurological disability, mortality, and to alter discharge disposition. Outcomes during the sub-acute and chronic stroke periods show that aphasia is associated with lower Functional Independence Measures (FIM) scores, longer stays in rehabilitation settings, poorer function in activities of daily living, and mortality. Factors that complicate the analysis of aphasia on post-stroke outcomes, however, include widely different systems of care across international settings that result in varying admission patterns to acute stroke units, allowable length of stays based on reimbursement, and criteria for rehabilitation placement. Aphasia arising from stroke is associated with worse outcomes both in the acute and chronic periods. Future research will have to incorporate disparate patterns in analytic models, and to take into account specific aphasia profiles and evolving methods of post-stroke speech-language therapy.

Modelling the potential impact of a sugar-sweetened beverage tax on stroke mortality, costs and health-adjusted life years in South Africa

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Mercy Manyema

2016-05-01

Full Text Available Abstract Background Stroke poses a growing human and economic burden in South Africa. Excess sugar consumption, especially from sugar-sweetened beverages (SSBs, has been associated with increased obesity and stroke risk. Research shows that price increases for SSBs can influence consumption and modelling evidence suggests that taxing SSBs has the potential to reduce obesity and related diseases. This study estimates the potential impact of an SSB tax on stroke-related mortality, costs and health-adjusted life years in South Africa. Methods A proportional multi-state life table-based model was constructed in Microsoft Excel (2010. We used consumption data from the 2012 South African National Health and Nutrition Examination Survey, previously published own and cross price elasticities of SSBs and energy balance equations to estimate changes in daily energy intake and BMI arising from increased SSB prices. Stroke relative risk, and prevalent years lived with disability estimates from the Global Burden of Disease Study and modelled disease epidemiology estimates from a previous study, were used to estimate the effect of the BMI changes on the burden of stroke. Results Our model predicts that an SSB tax may avert approximately 72 000 deaths, 550 000 stroke-related health-adjusted life years and over ZAR5 billion, (USD400 million in health care costs over 20 years (USD296-576 million. Over 20 years, the number of incident stroke cases may be reduced by approximately 85 000 and prevalent cases by about 13 000. Conclusions Fiscal policy has the potential, as part of a multi-faceted approach, to mitigate the growing burden of stroke in South Africa and contribute to the achievement of the target set by the Department of Health to reduce relative premature mortality (less than 60 years from non-communicable diseases by the year 2020.

Th17 in Animal Models of Rheumatoid Arthritis

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Motomu Hashimoto

2017-07-01

Full Text Available IL-17-secreting helper CD4 T cells (Th17 cells constitute a newly identified subset of helper CD4 T cells that play a key role in the development of rheumatoid arthritis (RA in its animal models. Recently, several models of spontaneous RA, which elucidate the mechanism of RA onset, have been discovered. These animal models shed new light on the role of Th17 in the development of autoimmune arthritis. Th17 cells coordinate inflammation and promote joint destruction, acting on various cells, including neutrophils, macrophages, synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17 cells under conditions of inflammation. In this review, the pathogenic role of Th17 cells in arthritis development, which was revealed by the recent animal models of RA, is discussed.

Experimental animal models for COPD: a methodological review

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Vahideh Ghorani

2017-05-01

The present review provides various methods used for induction of animal models of COPD, different animals used (mainly mice, guinea pigs and rats and measured parameters. The information provided in this review is valuable for choosing appropriate animal, method of induction and selecting parameters to be measured in studies concerning COPD.

Air Pollution and Ischemic Stroke Among Young Adults.

Science.gov (United States)

Yitshak Sade, Maayan; Novack, Victor; Ifergane, Gal; Horev, Anat; Kloog, Itai

2015-12-01

Studies have demonstrated consistent associations between cardiovascular illness and particulate matter (PM) stroke received less attention. We hypothesized that air pollution, an inflammation progenitor, can be associated with stroke incidence in young patients in whom the usual risk factors for stroke are less prevalent. We aimed to evaluate the association between stroke incidence and exposure to PM stroke between 2005 and 2012. Exposure assessment was based on a hybrid model incorporating daily satellite remote sensing data at 1-km spatial resolution. We performed case-crossover analysis, stratified by personal characteristics and distance from main roads. We identified 4837 stroke cases (89.4% ischemic stroke). Interquartile range of PM ischemic stroke and increases of interquartile range average concentrations of particulate matter ischemic stroke associated with PM among young adults. This finding can be explained by the inflammatory mechanism, linking air pollution and stroke. © 2015 American Heart Association, Inc.

A study on the influence of corona on currents and electromagnetic fields predicted by a nonlinear lightning return-stroke model

Science.gov (United States)

De Conti, Alberto; Silveira, Fernando H.; Visacro, Silvério

2014-05-01

This paper investigates the influence of corona on currents and electromagnetic fields predicted by a return-stroke model that represents the lightning channel as a nonuniform transmission line with time-varying (nonlinear) resistance. The corona model used in this paper allows the calculation of corona currents as a function of the radial electric field in the vicinity of the channel. A parametric study is presented to investigate the influence of corona parameters, such as the breakdown electric field and the critical electric field for the stable propagation of streamers, on predicted currents and electromagnetic fields. The results show that, regardless of the assumed corona parameters, the incorporation of corona into the nonuniform and nonlinear transmission line model under investigation modifies the model predictions so that they consistently reproduce most of the typical features of experimentally observed lightning electromagnetic fields and return-stroke speed profiles. In particular, it is shown that the proposed model leads to close vertical electric fields presenting waveforms, amplitudes, and decay with distance in good agreement with dart leader electric field changes measured in triggered lightning experiments. A comparison with popular engineering return-stroke models further confirms the model's ability to predict consistent electric field waveforms in the close vicinity of the channel. Some differences observed in the field amplitudes calculated with the different models can be related to the fact that current distortion, while present in the proposed model, is ultimately neglected in the considered engineering return-stroke models.

Animal Cancer Models of Skeletal Metastasis

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Catherine Hibberd

2013-01-01

Full Text Available The bony skeleton is one of the most common sites of metastatic spread of cancer and is a significant source of morbidity in cancer patients, causing pain and pathologic fracture, impaired ambulatory ability, and poorer quality of life. Animal cancer models of skeletal metastases are essential for better understanding of the molecular pathways behind metastatic spread and local growth and invasion of bone, to enable analysis of host-tumor cell interactions, identify barriers to the metastatic process, and to provide platforms to develop and test novel therapies prior to clinical application in human patients. Thus, the ideal model should be clinically relevant, reproducible and representative of the human condition. This review summarizes the current in vivo animal models used in the study of cancer metastases of the skeleton.

Child-Mediated Stroke Communication: findings from Hip Hop Stroke.

Science.gov (United States)

Williams, Olajide; DeSorbo, Alexandra; Noble, James; Gerin, William

2012-01-01

Low thrombolysis rates for acute ischemic stroke are linked to delays in seeking immediate treatment due to low public stroke awareness. We aimed to assess whether "Child-Mediated Stroke Communication" could improve stroke literacy of parents of children enrolled in a school-based stroke literacy program called Hip Hop Stroke. Parents of children aged 9 to 12 years from 2 public schools in Harlem, New York City, were recruited to participate in stroke literacy questionnaires before and after their child's participation in Hip Hop Stroke, a novel Child-Mediated Stroke Communication intervention delivered in school auditoriums. Parental recall of stroke information communicated through their child was assessed 1-week after the intervention. Fifth and sixth grade students (n=182) were enrolled into Hip Hop Stroke. One hundred two parents were approached in person to participate; 75 opted to participate and 71 completed both the pretest and post-test (74% response rate and 95% retention rate). Parental stroke literacy improved after the program; before the program, 3 parents of 75 (3.9%) were able to identify the 5 cardinal stroke symptoms, distracting symptom (chest pains), and had an urgent action plan (calling 911) compared with 21 of 71 parents (29.6%) postintervention (P<0.001). The FAST mnemonic was known by 2 (2.7%) of participants before the program versus 29 (41%) after program completion (P<0.001). Knowledge of stroke signs and symptoms remains low among residents of this high-risk population. The use of Child-Mediated Stroke Communication suggests that school children aged 9 to 12 years may be effective conduits of critical stroke knowledge to their parents.

Lanchester's attrition models and fights among social animals

OpenAIRE

Eldridge S. Adams; Michael Mesterton-Gibbons

2003-01-01

Lanchester's models of attrition during warfare have served as the basis for several predictions about conflicts between groups of animals. These models and their extensions describe rates of mortality during battles as functions of the number and fighting abilities of individuals in each group, allowing analysis of the determinants of group strength and of the cumulative numbers of casualties. We propose modifications to Lanchester's models to improve their applicability to social animals. I...

Research progress on animal models of Alzheimer's disease

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Wen DONG

2015-08-01

Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

Animal models of obesity and diabetes mellitus

DEFF Research Database (Denmark)

Kleinert, Maximilian; Clemmensen, Christoffer; Hofmann, Susanna M

2018-01-01

More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover......, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions. In this Review, we consolidate the key information on the currently...... available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models....

The impact of stroke unit care on outcome in a Scottish stroke population, taking into account case mix and selection bias.

Science.gov (United States)

Turner, Melanie; Barber, Mark; Dodds, Hazel; Dennis, Martin; Langhorne, Peter; Macleod, Mary Joan

2015-03-01

Randomised trials indicate that stroke unit care reduces morbidity and mortality after stroke. Similar results have been seen in observational studies but many have not corrected for selection bias or independent predictors of outcome. We evaluated the effect of stroke unit compared with general ward care on outcomes after stroke in Scotland, adjusting for case mix by incorporating the six simple variables (SSV) model, also taking into account selection bias and stroke subtype. We used routine data from National Scottish datasets for acute stroke patients admitted between 2005 and 2011. Patients who died within 3 days of admission were excluded from analysis. The main outcome measures were survival and discharge home. Multivariable logistic regression was used to estimate the OR for survival, and adjustment was made for the effect of the SSV model and for early mortality. Cox proportional hazards model was used to estimate the hazard of death within 365 days. There were 41 692 index stroke events; 79% were admitted to a stroke unit at some point during their hospital stay and 21% were cared for in a general ward. Using the SSV model, we obtained a receiver operated curve of 0.82 (SE 0.002) for mortality at 6 months. The adjusted OR for survival at 7 days was 3.11 (95% CI 2.71 to 3.56) and at 1 year 1.43 (95% CI 1.34 to 1.54) while the adjusted OR for being discharged home was 1.19 (95% CI 1.11 to 1.28) for stroke unit care. In routine practice, stroke unit admission is associated with a greater likelihood of discharge home and with lower mortality up to 1 year, after correcting for known independent predictors of outcome, and excluding early non-modifiable mortality. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Large Mammalian Animal Models of Heart Disease

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Paula Camacho

2016-10-01

Full Text Available Due to the biological complexity of the cardiovascular system, the animal model is an urgent pre-clinical need to advance our knowledge of cardiovascular disease and to explore new drugs to repair the damaged heart. Ideally, a model system should be inexpensive, easily manipulated, reproducible, a biological representative of human disease, and ethically sound. Although a larger animal model is more expensive and difficult to manipulate, its genetic, structural, functional, and even disease similarities to humans make it an ideal model to first consider. This review presents the commonly-used large animals—dog, sheep, pig, and non-human primates—while the less-used other large animals—cows, horses—are excluded. The review attempts to introduce unique points for each species regarding its biological property, degrees of susceptibility to develop certain types of heart diseases, and methodology of induced conditions. For example, dogs barely develop myocardial infarction, while dilated cardiomyopathy is developed quite often. Based on the similarities of each species to the human, the model selection may first consider non-human primates—pig, sheep, then dog—but it also depends on other factors, for example, purposes, funding, ethics, and policy. We hope this review can serve as a basic outline of large animal models for cardiovascular researchers and clinicians.

Quantifying links between stroke and risk factors: a study on individual health risk appraisal of stroke in a community of Chongqing.

Science.gov (United States)

Wu, Yazhou; Zhang, Ling; Yuan, Xiaoyan; Wu, Yamin; Yi, Dong

2011-04-01

The objective of this study is to investigate the risk factors of stroke in a community in Chongqing by setting quantitative criteria for determining the risk factors of stroke. Thus, high-risk individuals can be identified and laid a foundation for predicting individual risk of stroke. 1,034 cases with 1:2 matched controls (2,068) were chosen from five communities in Chongqing including Shapingba, Xiaolongkan, Tianxingqiao, Yubei Road and Ciqikou. Participants were interviewed with a uniform questionnaire. The risk factors of stroke and the odds ratios of risk factors were analyzed with a logistic regression model, and risk exposure factors of different levels were converted into risk scores using statistical models. For men, ten risk factors including hypertension (5.728), family history of stroke (4.599), and coronary heart disease (5.404), among others, were entered into the main effect model. For women, 11 risk factors included hypertension (5.270), family history of stroke (4.866), hyperlipidemia (4.346), among others. The related risk scores were added to obtain a combined risk score to predict the individual's risk of stoke in the future. An individual health risk appraisal model of stroke, which was applicable to individuals of different gender, age, health behavior, disease and family history, was established. In conclusion, personal diseases including hypertension, diabetes mellitus, etc., were very important to the prevalence of stoke. The prevalence of stroke can be effectively reduced by changing unhealthy lifestyles and curing the positive individual disease. The study lays a foundation for health education to persuade people to change their unhealthy lifestyles or behaviors, and could be used in community health services.

In vivo bioimpedance measurement of healthy and ischaemic rat brain: implications for stroke imaging using electrical impedance tomography

International Nuclear Information System (INIS)

Dowrick, T; Blochet, C; Holder, D

2015-01-01

In order to facilitate the imaging of haemorrhagic and ischaemic stroke using frequency difference electrical impedance tomography (EIT), impedance measurements of normal and ischaemic brain, and clotted blood during haemorrhage, were gathered using a four-terminal technique in an in vivo animal model, a first for ischaemic measurements. Differences of 5–10% in impedance were seen between the frequency spectrums of healthy and ischaemic brain, over the frequency range 0–3 kHz, while the spectrum of blood was predominately uniform. The implications of imaging blood/ischaemia in the brain using electrical impedance tomography are discussed, supporting the notion that it will be possible to differentiate stroke from haemorrhage. (paper)

Recurrent Stroke in Minor Ischemic Stroke or Transient Ischemic Attack With Metabolic Syndrome and/or Diabetes Mellitus.

Science.gov (United States)

Chen, Weiqi; Pan, Yuesong; Jing, Jing; Zhao, Xingquan; Liu, Liping; Meng, Xia; Wang, Yilong; Wang, Yongjun

2017-06-01

We aimed to determine the risk conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent stroke in patients with minor ischemic stroke or transient ischemic attack from the CHANCE (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events) trial. In total, 3044 patients were included. Patients were stratified into 4 groups: neither, METS only, DM only, or both. METS was defined using the Chinese Diabetes Society (CDS) and International Diabetes Foundation (IDF) definitions. The primary outcome was new stroke (including ischemic and hemorrhagic) at 90 days. A multivariable Cox regression model was used to assess the relationship of METS and DM status to the risk of recurrent stroke adjusted for potential covariates. Using the CDS criteria of METS, 53.2%, 17.2%, 19.8%, and 9.8% of patients were diagnosed as neither, METS only, DM only, and both, respectively. After 90 days of follow-up, there were 299 new strokes (293 ischemic, 6 hemorrhagic). Patients with DM only (16.1% versus 6.8%; adjusted hazard ratio 2.50, 95% CI 1.89-3.39) and both (17.1% versus 6.8%; adjusted hazard ratio 2.76, 95% CI 1.98-3.86) had significantly increased rates of recurrent stroke. No interaction effect of antiplatelet therapy by different METS or DM status for the risk of recurrent stroke ( P =0.82 for interaction in the fully adjusted model of CDS) was observed. Using the METS (IDF) criteria demonstrated similar results. Concurrent METS and DM was associated with an increased risk of recurrent stroke in patients with minor stroke and transient ischemic attack. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Animal models for evaluation of oral delivery of biopharmaceuticals

DEFF Research Database (Denmark)

Harloff-Helleberg, Stine; Nielsen, Line Hagner; Nielsen, Hanne Mørck

2017-01-01

of systems for oral delivery of biopharmaceuticals may result in new treatment modalities to increase the patient compliance and reduce product cost. In the preclinical development phase, use of experimental animal models is essential for evaluation of new formulation designs. In general, the limited oral...... bioavailability of biopharmaceuticals, of just a few percent, is expected, and therefore, the animal models and the experimental settings must be chosen with utmost care. More knowledge and focus on this topic is highly needed, despite experience from the numerous studies evaluating animal models for oral drug...... delivery of small molecule drugs. This review highlights and discusses pros and cons of the most currently used animal models and settings. Additionally, it also looks into the influence of anesthetics and sampling methods for evaluation of drug delivery systems for oral delivery of biopharmaceuticals...

Temporal and Spatial Characterization of Gait Pattern in Rodents as an Animal model of Cerebrovascular Lesion

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Jaison D Cucarián

2017-09-01

Full Text Available Animal experimentation is crucial for the advance in the understanding of pathophysiological mechanisms and their application on both clinical diagnosis and neuro-rehabilitation. Particularly, rodent brain lesion is commonly used in the modeling of locomotor, somatosensory and cognitive symptoms. The automated rodent gait analysis has been proposed as a tool for studying locomotor and sensory abilities and its use includes the identification of functional alterations, structural adaptations as well as neuro-rehabilitation mechanisms. From that standpoint, the effectiveness of many therapeutic intervention (i.e. physical exercises has been documented in rodents and humans. The translation from experimental data to clinical conditions requires the continuous collaboration and feedback between researchers and health clinicians looking for the selection of the best rehabilitation protocols obtained from animal research. Here we will show some locomotor alterations, the traditional methods used to assess motor dysfunction and gait abnormalities in rodent models with stroke. The aim of this review is to show some motor deficiencies and some methods used to establish gait disturbances in rodents with cerebrovascular lesion. The review included the search of defined terms (MeSH in PychINFO, Medline and Web of Science, between January 2000 and January 2017. Qualitative and narrative reports, dissertations, end course works and conference resumes were discarded. The review focuses on some clinical signs, their effects on rodent locomotor activity, some methodologies used to create lesion and to study motor function, some assessment methods and some translational aspects.

Embolus radiolabelling in a new canine model

International Nuclear Information System (INIS)

Kaufman, H.H.; Huchton, J.D.; Woo, J.; Cannon, D.C.; Anderson, J.H.

1980-01-01

Embolus radiolabelling with 131 I fibrinogen was studied in a canine model of internal carotid artery embolization. The dog was chosen as the experimental animal because of its maxillocarotid artery which permits collateral flow round the occlusion and helps to prevent strokes. Clot was prepared by incubating blood at room temperature to inactivate plasminogen activators and then refrigerating it to promote clot retraction. Emboli persisting 48 hours were seen in 80% of animals. Major strokes were not seen when 0.25 to 0.30 cm 3 were used. Autoradiography and well counting revealed uptake of isotope. The test, when refined, should provide a tool for the investigation of thromboemboli. (author)

Animal models for HIV/AIDS research

Science.gov (United States)

Hatziioannou, Theodora; Evans, David T.

2015-01-01

The AIDS pandemic continues to present us with unique scientific and public health challenges. Although the development of effective antiretroviral therapy has been a major triumph, the emergence of drug resistance requires active management of treatment regimens and the continued development of new antiretroviral drugs. Moreover, despite nearly 30 years of intensive investigation, we still lack the basic scientific knowledge necessary to produce a safe and effective vaccine against HIV-1. Animal models offer obvious advantages in the study of HIV/AIDS, allowing for a more invasive investigation of the disease and for preclinical testing of drugs and vaccines. Advances in humanized mouse models, non-human primate immunogenetics and recombinant challenge viruses have greatly increased the number and sophistication of available mouse and simian models. Understanding the advantages and limitations of each of these models is essential for the design of animal studies to guide the development of vaccines and antiretroviral therapies for the prevention and treatment of HIV-1 infection. PMID:23154262

Stroke Treatments

Science.gov (United States)

... Stroke Association.org Professionals for Stroke Association.org Shop for Stroke Association.org Support for Stroke Association. ... works by dissolving the clot and improving blood flow to the part of the brain being deprived ...

Post-stroke depression among stroke survivors attending two ...

African Journals Online (AJOL)

Background: The burden of stroke worldwide is increasing rapidly. There is paucity of data on post-stroke depression (PSD) among stroke survivors in Uganda, despite the high prevalence of PSD reported elsewhere. Methods: In a cross-sectional study, we assessed adult participants with confirmed first stroke with a ...

Animal Migraine Models for Drug Development

DEFF Research Database (Denmark)

Jansen-Olesen, Inger; Tfelt-Hansen, Peer; Olesen, Jes

2013-01-01

Migraine is number seven in WHO's list of all diseases causing disability and the third most costly neurological disorder in Europe. Acute attacks are treatable by highly selective drugs such as the triptans but there is still a huge unmet therapeutic need. Unfortunately, drug development...... for headache has almost come to a standstill partly because of a lack of valid animal models. Here we review previous models with emphasis on optimal characteristics of a future model. In addition to selection of animal species, the method of induction of migraine-like changes and the method of recording...... responses elicited by such measures are crucial. The most naturalistic way of inducing attacks is by infusion of endogenous signaling molecules that are known to cause migraine in patients. The most valid response is recording of neural activity in the trigeminal system. The most useful headache related...

Optogenetics in animal model of alcohol addiction

Science.gov (United States)

Nalberczak, Maria; Radwanska, Kasia

2014-11-01

Our understanding of the neuronal and molecular basis of alcohol addiction is still not satisfactory. As a consequence we still miss successful therapy of alcoholism. One of the reasons for such state is the lack of appropriate animal models which would allow in-depth analysis of biological basis of addiction. Here we will present our efforts to create the animal model of alcohol addiction in the automated learning device, the IntelliCage setup. Applying this model to optogenetically modified mice with remotely controlled regulation of selected neuronal populations by light may lead to very precise identification of neuronal circuits involved in coding addiction-related behaviors.

Animal Models of Diverticulosis: Review and Recommendations.

Science.gov (United States)

Patel, Bhavesh; Guo, Xiaomei; Noblet, Jillian; Chambers, Sean; Kassab, Ghassan S

2018-06-01

Diverticulosis is a structural alteration of the colon tissue characterized by the development of pouch-like structures called diverticula. It afflicts a significant portion of the population in Western countries, with a higher prevalence among the elderly. Diverticulosis is believed to be the result of a synergetic interaction between inherent tissue weakness, diet, colonic microstructure, motility, and genetic factors. A validated etiology has, however, not yet been established. Non-surgical treatment is currently lacking due to this poor understanding, and surgical colon resection is the only long-term solution following recurrent complications. With rising prevalence, the burden of diverticulosis on patients and hospital resources has increased over the past several years. More efficient and less invasive treatment approaches are, thus, urgently needed. Animal models of diverticulosis are crucial to enable a preclinical assessment and evaluation of such novel approaches. This review discusses the animal models of diverticulosis that have been proposed to date. The current models require either a significant amount of time to develop diverticulosis, present a relatively low success rate, or seriously deteriorate the animals' systemic health. Recommendations are thus provided to address these pitfalls through the selection of a suitable animal and the combination of multiple risk factors for diverticulosis.

Stop staring facial modeling and animation done right

CERN Document Server

Osipa, Jason

2010-01-01

The de facto official source on facial animation—now updated!. If you want to do character facial modeling and animation at the high levels achieved in today's films and games, Stop Staring: Facial Modeling and Animation Done Right, Third Edition , is for you. While thoroughly covering the basics such as squash and stretch, lip syncs, and much more, this new edition has been thoroughly updated to capture the very newest professional design techniques, as well as changes in software, including using Python to automate tasks.: Shows you how to create facial animation for movies, games, and more;

The Characterization of Deqi during Moxibustion in Stroke Rats

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Zhimai Lv

2013-01-01

Full Text Available The efficacy of acupuncture and moxibustion is closely related to Deqi phenomenons, which are some subjective feelings. However, no one has reported the objective characterization of Deqi. Our preliminary research has found a phenomenon of tail temperature increasing (TTI obviously in some stroke rats by suspended moxibustion at the acupoint dà zhuī (DU 14, which is similar to one characterization of Deqi during moxibustion that moxibustion heat is transferred from the original moxibustion acupoint to the other areas of the body. We wonder whether TTI is the objective indicator of Deqi characterization in animals. The present study showed that the stroke rat’s recovery was also associated with TTI phenomenon. This suggests that TTI phenomenon is one objective characterization of the Deqi in stroke rats. Application of the TTI phenomenon contributes to explore the physiological mechanism of Deqi.

Stroke Location Is an Independent Predictor of Cognitive Outcome.

Science.gov (United States)

Munsch, Fanny; Sagnier, Sharmila; Asselineau, Julien; Bigourdan, Antoine; Guttmann, Charles R; Debruxelles, Sabrina; Poli, Mathilde; Renou, Pauline; Perez, Paul; Dousset, Vincent; Sibon, Igor; Tourdias, Thomas

2016-01-01

On top of functional outcome, accurate prediction of cognitive outcome for stroke patients is an unmet need with major implications for clinical management. We investigated whether stroke location may contribute independent prognostic value to multifactorial predictive models of functional and cognitive outcomes. Four hundred twenty-eight consecutive patients with ischemic stroke were prospectively assessed with magnetic resonance imaging at 24 to 72 hours and at 3 months for functional outcome using the modified Rankin Scale and cognitive outcome using the Montreal Cognitive Assessment (MoCA). Statistical maps of functional and cognitive eloquent regions were derived from the first 215 patients (development sample) using voxel-based lesion-symptom mapping. We used multivariate logistic regression models to study the influence of stroke location (number of eloquent voxels from voxel-based lesion-symptom mapping maps), age, initial National Institutes of Health Stroke Scale and stroke volume on modified Rankin Scale and MoCA. The second part of our cohort was used as an independent replication sample. In univariate analyses, stroke location, age, initial National Institutes of Health Stroke Scale, and stroke volume were all predictive of poor modified Rankin Scale and MoCA. In multivariable analyses, stroke location remained the strongest independent predictor of MoCA and significantly improved the prediction compared with using only age, initial National Institutes of Health Stroke Scale, and stroke volume (area under the curve increased from 0.697-0.771; difference=0.073; 95% confidence interval, 0.008-0.155). In contrast, stroke location did not persist as independent predictor of modified Rankin Scale that was mainly driven by initial National Institutes of Health Stroke Scale (area under the curve going from 0.840 to 0.835). Similar results were obtained in the replication sample. Stroke location is an independent predictor of cognitive outcome (MoCA) at 3

Lipid management in the prevention of stroke: a meta-analysis of fibrates for stroke prevention

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Zhou Yu-Hao

2013-01-01

Full Text Available Abstract Background Fibrates has been extensively used to improve plasma lipid levels and prevent adverse cardiovascular outcomes. However, the effect of fibrates on stroke is unclear at the present time. We therefore carried out a comprehensive systematic review and meta-analysis to evaluate the effects of fibrates on stroke. Methods We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings to identify studies for our analysis. We included randomized placebo controlled trials which reported the effects of fibrates on stroke. Relative risk (RR was used to measure the effect of fibrates on the risk of stroke under random effect model. The analysis was further stratified by factors that could affect the treatment effects. Results Overall, fibrate therapy was not associated with a significant reduction on the risk of stroke (RR, 1.02, 95% CI, 0.90 to 1.16, P = 0.78. In the subgroup analyses, we observed that gemfibrozil therapy showed a beneficial effect on stroke (RR, 0.72, 95% CI, 0.53 to 0.98, P = 0.04. Similarly, fibrate therapy comparing to placebo had no effect on the incidence of fatal stroke. Subgroup analysis suggested that fibrate therapy showed an effect on fatal stroke when the Jadad score more than 3 (RR, 0.41, 95% CI, 0.17 to 1.00, P = 0.049. Furthermore, a sensitivity analysis indicated that fibrate therapy may play a role in fatal stroke (RR, 0.49, 95% CI, 0.26 to 0.93, P = 0.03 for patients with previous diabetes, cardiovascular disease or stroke. Conclusions Our study indicated that fibrate therapy might play an important role in reducing the risk of fatal stroke in patients with previous diabetes, cardiovascular disease or stroke. However, it did not have an effect on the incidence of stroke.

Excessive Premature Atrial Complexes and the Risk of Recurrent Stroke or Death in an Ischemic Stroke Population.

Science.gov (United States)

Vinther, Kristina H; Tveskov, Claus; Möller, Sören; Auscher, Soren; Osmanagic, Armin; Egstrup, Kenneth

2017-06-01

Our aim was to investigate the association of premature atrial complexes and the risk of recurrent stroke or death in patients with ischemic stroke in sinus rhythm. In a prospective cohort study, we used 24-hour Holter recordings to evaluate premature atrial complexes in patients consecutively admitted with ischemic strokes. Excessive premature atrial complexes were defined as >14 premature atrial complexes per hour and 3 or more runs of premature atrial complexes per 24 hours. During follow-up, 48-hour Holter recordings were performed after 6 and 12 months. Among patients in sinus rhythm, the association of excessive premature atrial complexes and the primary end point of recurrent stroke or death were estimated in both crude and adjusted Cox proportional hazards models. We further evaluated excessive premature atrial complexes contra atrial fibrillation in relation to the primary end point. Of the 256 patients included, 89 had atrial fibrillation. Of the patients in sinus rhythm (n = 167), 31 had excessive premature atrial complexes. During a median follow-up of 32 months, 50 patients (30% of patients in sinus rhythm) had recurrent strokes (n = 20) or died (n = 30). In both crude and adjusted models, excessive premature atrial complexes were associated with the primary end point, but not with newly diagnosed atrial fibrillation. Compared with patients in atrial fibrillation, those with excessive premature atrial complexes had similarly high risks of the primary end point. In patients with ischemic stroke and sinus rhythm, excessive premature atrial complexes were associated with a higher risk of recurrent stroke or death. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

ABO Blood Type and Stroke Risk: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

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Zakai, Neil A.; Judd, Suzanne E.; Alexander, Kristine; McClure, Leslie A.; Kissela, Brett M.; Howard, George; Cushman, Mary

2016-01-01

Background ABO blood type is an inherited trait associated with coagulation factor levels and vascular outcomes. Objectives To assess the association of blood type with stroke and whether blood type contributes to racial disparities in stroke in the United States. Patients and Methods The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study recruited 30,239 participants between 2003-07. Using a case-cohort design, blood type was genotyped in 646 participants with stroke and a 1,104 participant cohort random sample. Cox models adjusting for Framingham stroke risk factors assessed the association of blood type with stroke. Results Over 5.8 years of follow-up, blood types A or B versus type O were not associated with stroke. Blood type AB versus O was associated with an increased risk of stroke (adjusted HR 1.83; 95% CI 1.01, 3.30). The association of blood type AB versus O was greater in those without diabetes (adjusted HR 3.33; 95% CI 1.61, 6.88) than those with diabetes (adjusted HR 0.49; 95% CI 0.17, 1.44) (p-interaction = 0.02). Factor VIII levels accounted for 60% (95% CI 11%, 98%) of the association of AB blood type and stroke risk. Conclusion Blood type AB is associated with an increased risk of stroke that is not attenuated by conventional stroke risk factors and factor VIII levels were associated with 60% of the association. While blood type AB is rare in the U.S. population, it is a significant stroke risk factor and may play an important role in stroke risk in these individuals. PMID:24444093

Mridangam stroke dataset

OpenAIRE

CompMusic

2014-01-01

The audio examples were recorded from a professional Carnatic percussionist in a semi-anechoic studio conditions by Akshay Anantapadmanabhan using SM-58 microphones and an H4n ZOOM recorder. The audio was sampled at 44.1 kHz and stored as 16 bit wav files. The dataset can be used for training models for each Mridangam stroke. /n/nA detailed description of the Mridangam and its strokes can be found in the paper below. A part of the dataset was used in the following paper. /nAkshay Anantapadman...

Reduced blood brain barrier breakdown in P-selectin deficient mice following transient ischemic stroke: a future therapeutic target for treatment of stroke

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Petterson Jodie

2010-02-01

Full Text Available Abstract Background The link between early blood- brain barrier (BBB breakdown and endothelial cell activation in acute stroke remain poorly defined. We hypothesized that P-selectin, a mediator of the early phase of leukocyte recruitment in acute ischemia is also a major contributor to early BBB dysfunction following stroke. This was investigated by examining the relationship between BBB alterations following transient ischemic stroke and expression of cellular adhesion molecule P-selectin using a combination of magnetic resonance molecular imaging (MRMI, intravital microscopy and immunohistochemistry. MRMI was performed using the contrast, gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA conjugated to Sialyl Lewis X (Slex where the latter is known to bind to activated endothelium via E- or P selectins. Middle cerebral artery occlusion was induced in male C57/BL 6 wild-type (WT mice and P-selectin-knockout (KO mice. At 24 hours following middle cerebral artery occlusion, T1 maps were acquired prior to and following contrast injection. In addition to measuring P- and E-selectin expression in brain homogenates, alterations in BBB function were determined immunohistochemically by assessing the extravasation of immunoglobulin G (IgG or staining for polymorphonuclear (PMN leukocytes. In vivo assessment of BBB dysfunction was also investigated optically using intravital microscopy of the pial circulation following the injection of Fluorescein Isothiocyanate (FITC-dextran (MW 2000 kDa. Results MRI confirmed similar infarct sizes and T1 values at 24 hours following stroke for both WT and KO animals. However, the blood to brain transfer constant for Gd DTPA (Kgd demonstrated greater tissue extravasation of Gd DTPA in WT animals than KO mice (P 1 stroke -Δ T1 contralateral control cortex, decreased significantly in the Gd-DTPA(sLeX group compared to Gd-DTPA, indicative of sLeX mediated accumulation of the targeted contrast agent. Regarding BBB

PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model.

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Low, Pei Ching; Manzanero, Silvia; Mohannak, Nika; Narayana, Vinod K; Nguyen, Tam H; Kvaskoff, David; Brennan, Faith H; Ruitenberg, Marc J; Gelderblom, Mathias; Magnus, Tim; Kim, Hyun Ah; Broughton, Brad R S; Sobey, Christopher G; Vanhaesebroeck, Bart; Stow, Jennifer L; Arumugam, Thiruma V; Meunier, Frédéric A

2014-03-14

Stroke is a major cause of death worldwide and the leading cause of permanent disability. Although reperfusion is currently used as treatment, the restoration of blood flow following ischaemia elicits a profound inflammatory response mediated by proinflammatory cytokines such as tumour necrosis factor (TNF), exacerbating tissue damage and worsening the outcomes for stroke patients. Phosphoinositide 3-kinase delta (PI3Kδ) controls intracellular TNF trafficking in macrophages and therefore represents a prospective target to limit neuroinflammation. Here we show that PI3Kδ inhibition confers protection in ischaemia/reperfusion models of stroke. In vitro, restoration of glucose supply following an episode of glucose deprivation potentiates TNF secretion from primary microglia-an effect that is sensitive to PI3Kδ inhibition. In vivo, transient middle cerebral artery occlusion and reperfusion in kinase-dead PI3Kδ (p110δ(D910A/D910A)) or wild-type mice pre- or post-treated with the PI3Kδ inhibitor CAL-101, leads to reduced TNF levels, decreased leukocyte infiltration, reduced infarct size and improved functional outcome. These data identify PI3Kδ as a potential therapeutic target in ischaemic stroke.

Evaluation of stroke services in Anglia stroke clinical network to examine the variation in acute services and stroke outcomes

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George Abraham

2011-02-01

Full Text Available Abstract Background Stroke is the third leading cause of death in developed countries and the leading cause of long-term disability worldwide. A series of national stroke audits in the UK highlighted the differences in stroke care between hospitals. The study aims to describe variation in outcomes following stroke and to identify the characteristics of services that are associated with better outcomes, after accounting for case mix differences and individual prognostic factors. Methods/Design We will conduct a cohort study in eight acute NHS trusts within East of England, with at least one year of follow-up after stroke. The study population will be a systematically selected representative sample of patients admitted with stroke during the study period, recruited within each hospital. We will collect individual patient data on prognostic characteristics, health care received, outcomes and costs of care and we will also record relevant characteristics of each provider organisation. The determinants of one year outcome including patient reported outcome will be assessed statistically with proportional hazards regression models. Self (or proxy completed EuroQol (EQ-5D questionnaires will measure quality of life at baseline and follow-up for cost utility analyses. Discussion This study will provide observational data about health service factors associated with variations in patient outcomes and health care costs following hospital admission for acute stroke. This will form the basis for future RCTs by identifying promising health service interventions, assessing the feasibility of recruiting and following up trial patients, and provide evidence about frequency and variances in outcomes, and intra-cluster correlation of outcomes, for sample size calculations. The results will inform clinicians, public, service providers, commissioners and policy makers to drive further improvement in health services which will bring direct benefit to the patients.

Animal Models for the Study of Female Sexual Dysfunction