Day2

  • Inra Research Centre, France
  • Title:Stunning and Slaughter Techniques: Neurological Mechanisms and Indicators of Consciousness and Unconsciousness
  • Time :

Abstract

At slaughter, animals are generally stunned before bleeding, but society and field workers sometimes question efficacy. Recently, work was undertaken to understand better the neurobiological mechanisms involved in the stunning and killing process of animals. The mechanisms underlying the loss of consciousness depend on the technique used: mechanical, electrical or gas stunning. Direct exsanguination without prior stun, for religious slaughter, causes also a loss of consciousness, before inducing death. Stunning techniques use stun guns, electrified devices or gas mixtures. The principles of stunning and bleeding involve mechanical shock waves and the mechanical destruction of neurons, electrical fields, the reduction or arrest of cerebral blood circulation, or high and/or low levels of CO2 and/or O2, respectively, in inspired air. Effects involve cerebral anoxia or ischemia, the depolarisation, acidification and/or the destruction of brain neurons. Targeted brain structures are the reticular formation, the ascending reticular activating system or thalamus, or the cerebral hemispheres in a general manner. Some of the techniques induce an immediate loss of consciousness, other techniques a progressive loss of consciousness.
To ensure that the animal is unconscious, before further processing, indicators of consciousness and of unconsciousness are verified. They evaluate different aspects of cerebral functioning. As they are imprecise, it necessary to monitor several. As animals may regain consciousness, they are observed until the end of bleeding. Animals are considered unconscious if signs of consciousness are absent, and signs of unconsciousness are present.
Examples of indicators of unconsciousness are the absence of standing posture and of righting movements, the absence of a corneal reflex and respiratory arrest. Indicators of consciousness are the standing posture, coordinated righting movements, specifies-specific vocalizations and a response to the threat test. Often various movements are observed following the stun and during bleeding, including eye tracking, eyeball rotation, nystagmus, head and neck movements and leg paddling. Their presence often leads to confusion on the field as they may be reflex movements, but sometimes they indicate consciousness. Their interpretation needs further discussion.
The techniques used to diagnose brain death in humans cannot be used in the slaughterhouse. Under field conditions, at the end of bleeding, the absence of breathing and of brainstem reflexes and the adequacy of the exsanguination are verified. If these three aspects are confirmed, in the context of the slaughterhouse and at this stage of the slaughter process, the loss of vital functions is irreversible and the animal considered dead.

  • Dankook University College of Medicine, Kore
  • Title:Endovascular Treatment with Stents in Ruptured Complex Aneurysms
  • Time :

Abstract

Stent using in intracranial aneurysms has been avoided by most operators because of concerns about the risk of using dual antiplatelet therapy in the setting of acute SAH.
In case of posterior communicating artery aneurysm with fetal type artery incorporated on aneurysm or broad necked appearance, it was regarded as very difficult to treat endovascularly. However with intracranial stenting maneuver introducing recently, it can be treated completely by retrograde navigation of stent through anterior communicating artery and further coiling with staged approach.
And flow diverters also play important role to treat aneurysms.
The author introduces several technical extensions to overcome the pitfalls in treating the intracranial
complex aneurysms.

Biography

Young Joon Kim, Korean neurosurgeon, educator. Achievements include research in endovascular aneurysm coiling with stent & endovascular care of acute stroke. Member of Korean Society Neurosurgery (board directors since 1998), Korean Society Intravascular Neurosurgery (president 2002-2004).

  • Ariel University, Israel
  • Title:Intensity-Dependent Effects of Exercise Training in Experimental Multiple Sclerosis
  • Time :

Abstract

Background: Exercise training (ET) has beneficial effects in Multiple Sclerosis (MS)patients and in experimental autoimmuneencephalomyelitis (EAE), the animal model of MS. However, the intensity-dependent effects of ET on the systemic immune system and/or the central nervous system (CNS) remain undefined.
Purpose: To compare the systemic immune-modulatory- and direct neuroprotectiveeffects of moderate vs. high intensity ET protocols on EAE development.
Methods: Healthy mice performed moderate- or high-intensity treadmill runningprograms. Proteolipid protein (PLP)-induced transfer EAE was utilized to enable differentiation between effects of ET on systemic autoimmunity vs. direct effects on the CNS. To investigate the immune-modulatory effects of ET, lymph-node (LN)-T cells from trained- vs. sedentary donor mice were transferred to naïve recipients. EAE severity in recipient mice was assessed by clinical assessment and histopathological analysis. LN-T cells derived from donor trained vs. sedentary PLP-immunized mice were analyzed in vitro for proliferation by flow cytometry analysis, and for cytokine and chemokine receptor gene expression using real-time PCR. To investigate the neuroprotective effects of ET, PLP-reactive, encephalitogenic T cells were transferred into recipient mice that underwent the training program prior to EAE transfer, and disease severity was compared to that in recipient sedentary mice.
Results: High-intensity training in healthy donor mice induced significantly greater inhibition than moderate-intensity training on proliferation and generation of encephalitogenic T-cells in response to PLP-immunization, and on EAE severity upon their transfer into recipient mice. Additionally, whereas moderate intensity ET did not have direct neuroprotective effects, transfer of PLP-reactive, encephalitogenic LN-T cells resulted in less severe EAE in recipient mice that were subjected to high intensity training program prior to EAE transfer.
Conclusions: Our data, obtained by using a unique experimental design, indicate superior effects of high intensity training on both systemic immune-modulation and direct neuroprotection to inhibit autoimmunity in EAE. This study is of clinical significance and may provide a basis for defining exercise recommendations (that are currently lacking) for MS patients.

Biography

Prof.Ofira Einstein graduated physical therapy school in 1999 (B.P.T.) and doctorate studies in neurobiology in 2006 (Ph.D.). She joined as a faculty of the Physical Therapy department at Ariel University in 2009 and served as the head of the department in years 2011-2017. Prof. Einstein’s research areas are neuro-immunology and neuroregeneration. Her first studies concerned on the neurobiology of neural stem cells and cell therapy, specifically on animal models of human Multiple Sclerosis (MS). Her work published in 2003 was the first to show that transplanted neural stem cells have anti-inflammatory effects on the rodent brain. This finding was a breakthrough for further research of her group, as well as other research groups around the world. Her current research focuses on neuro-immunological, neuro-protective and neuroregenerative effects of exercise training on neuro-inflammatory and neuro-degenerative diseases. These studies are particularly carried on experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Prof. Einstein’s studies involve animal physical training, clinical evaluations, histopathological analyses, cell cultures and molecular biology techniques.

  • Tongji University, China
  • Title:Multilevel Metric Rank Match for Person Re-Identification
  • Time :

Abstract

Metric learning is one of the important ways to improve the person re-identification (ReID)
accurate, of which triplet loss is the most effect metric learning method. However, triplet loss only
ranks the extracted feature at the end of the network, in this paper, we propose a multilevel metric
rank match (MMRM) method, which ranks the extracted feature on multilevel of the network. At
each rank level, the extracted features are ranked to find the hard sample pairs and the back
transfer triplet loss. Each rank level has different penalize value to adjust the network, in which
the value is bigger with the deeper level of the whole network. Experiment results on CUHK03,
Market1501 and DukeMTMC datasets indicate that The MMRM algorithm can outperform the
previous state-of-the-arts.

Biography

Chao Wang is now a Ph.D. candidate with the Institute of Machine Learning and Systems Biology,
School of Electronics and Information Engineering, Tongji University, China. He received the B.S.
degree from Anhui University, China, in 2006, and the M.S. degree from University of Science
and Technology of China, in 2009. From Nov. 2009 to Dec. 2010, he worked as Research
Associate in Nanyang Technological University. From Jan. to May 2011, he worked as Research
Associate in Jacobs University, Bremen Germany. From June 2011 to Aug. 2012, he worked as
Research Associate in Shenzhen Institute of advanced technology, Chinese Academy of Sciences.
From Sept. 2012 to Mar. 2013, he worked as Engineer in Huawei Technology Co., Ltd. He now
works at Suzhou University. His research focuses on pattern recognition, deep learning and image
processing.

  • Cairo University, Egypt
  • Title:Renin Angiotensin System Activation in Diabetes Induced Cognitive Impairment
  • Time :

Abstract

There is a great concern in learning and memory deficits that develop over time in patients with poorly controlled diabetes. Hyperactivity of the renin- angiotensin system (RAS) is directly associated with β-cell dysfunction and diabetic complications, including cognitive impairment. There is correlation between RAS components found in areas of the brain and cognition, behavior and locomotion. RAS modifiers; aliskiren and captopril protective and molecular effects were investigated on cognitive deficits in the rat hippocampus, a key brain region responsible for memory and cognition. Poorly controlled STZ-diabetic rats were injected subcutaneously with ineffective daily doses of insulin for 4 weeks. The hyperglycemia and pancreatic atrophy caused memory disturbances that were identifiable in behavioral tests, hippocampal neurodegeneration,and the following significant changes in the hippocampus, increases in the inflammatory marker interleukin 1β, cholinesterase, the oxidative stress marker malondialdehyde and protein expression of phosphorylated extracellular-signal-regulated kinase and glycogen synthase kinase-3 beta versus decrease in the antioxidant reduced glutathione and protein expression of phosphorylated glycogen synthase kinase-3 beta. Blocking RAS with either drug along with insulin restored all previously mentioned parameters to normal. Aliskiren stabilized the blood glucose level and restored normal pancreatic integrity and hippocampal MDA level. Aliskiren showed superior protection against the hippocampal degeneration displayed in the earlier behavioral modification in the passive avoidance test and aliskiren group outperformed the control group in the novel object recognition test. We, therefore, conclude that aliskiren and captopril reversed the diabetic state and cognitive deficits through the renin inhibitory effect and blockade of
RAS. Captopril protective effect is related to a reduction in Ang II synthesis. At last, dwindling RAS activity reduce oxidative stress, inflammation state, and modulating protein expression.

Biography

Madonna Magdy Youssef, MSc, received pharmacy degree from Ain Shams University and master’s degree in the field of pharmacology at faculty of pharmacy, Cairo University in 2019. Currently employed as quality assurance specialist in Egyptian Drug Authorization (EDA), granted a quality management diploma in 2020. The Ph.D. research work is in progress in fruitful collaboration with the National Research Center and the Academy of Scientific Research. The study related to neurocognitive protection from Alzheimer’s disease for healthy aging as well as investigation of possible enhancement of insulin release and sensitivity for diabetic patients. Serve as a reviewer for Elsevier international journal “Pharmacology and Therapeutics”. Research interests are overly concerned with critical pathways and applicable drugs related to neurological and cognitive disorders, diabetes as well as immunological diseases.

  • University of Illinois at Chicago, USA
  • Title:Predicting Autism Spectrum Disorder Using Domain-Adaptive Cross-Site Evaluation
  • Time :

Abstract

The advances in neuroimaging methods reveal that resting-state functional fMRI (rs-fMRI) connectivity measures can be potential diagnostic biomarkers for autism spectrum disorder (ASD). Recent data sharing projects help us replicating the robustness of these biomarkers in different acquisition conditions or preprocessing steps across larger numbers of individuals or
sites. It is necessary to validate the previous results by using data from multiple sites by diminishing the site variations. We investigated partial least square regression (PLS), a domain adaptive method to adjust the effects of multicenter acquisition. A sparse Multivariate Pattern Analysis (MVVPA) framework in a leave one site out cross validation (LOSOCV) setting has been proposed to discriminate ASD from healthy controls using data from six sites in the Autism Brain Imaging Data Exchange (ABIDE). Our results showed that two or more informative connections are Dorsolateral Prefrontal Cortex, Somatosensory Association Cortex, Primary Auditory Cortex, Inferior Temporal Gyrus and Temporopolar area. These interrupted regions are involved in executive function, speech, visual perception, sense and language which are associated with ASD. Our findings may support early clinical diagnosis or risk determination by identifying neurobiological markers to distinguish between ASD and healthy controls.

Biography

Dr. Bhaumik is a research assistant professor at Biostatistical Research Center, in the Department of Psychiatry. Her research focuses on Longitudinal Data Analysis, Multivariate Statistical analysis, Graph Theory and applications of Machine Learning Algorithms to Neuroscience and other fields.

  • University of California, USA
  • Title:Integrated Stress Response Inhibitor Reverses Sex-Dependent Behavioral and Cell-Specific Deficits After Mild Repetitive Head Trauma
  • Time :

Abstract
Mild repetitive traumatic brain injury (rTBI) induces chronic behavioral and cognitive alterations and increases the risk for dementia. Currently there are no therapeutic strategies to prevent or mitigate chronic deficits associated with rTBI. We previously developed an animal model of rTBI that recapitulates some of the cognitive and behavioral deficits observed in humans. Here we report that rTBI results in an increase in risk-taking behavior in male but not female mice. This behavioral phenotype is associated with cell-specific synaptic alterations in the type A subtype of layer V pyramidal neurons in the medial prefrontal cortex (mPFC). Strikingly, by briefly treating animals’ weeks after injuries with ISRIB, a selective inhibitor of the integrated stress response (ISR), we permanently reverse the increased risk-taking behavioral phenotype and restore cell-specific synaptic function in the affected mice. Our results indicate that targeting the ISR even at late time points after injury can permanently reverse behavioral changes. As such, pharmacological inhibition of the ISR emerges as a promising avenue to combat rTBI-induced behavioral dysfunction.

Biography
Susanna Rosi is a Professor in the Departments of Physical Therapy Rehabilitation Science and Neurological Surgery and the Director of Neurocognitive Research in the Brain and Spinal Injury Center. She is a member of the UCSF Weill Institute for Neurosciences, Kavli Institute for Fundamental Neuroscience, Hellen Diller Cancer Center, Neuroscience Graduate Program, Biomedical Science Graduate Program. Originally from Tuscany, Dr. Rosi earned her undergraduate degree and PhD in Biology from the University of Florence, Italy. She trained in the Neural System Memory and Aging center at the University of Arizona before becoming a Faculty Member of UCSF. Her research is focused on understanding the mechanisms responsible for the cognitive dysfunctions observed after brain injury. Her final goal is to identify diagnostic tools for treatment and prevention. She demonstrated the key role that neuroinflammation plays in the development of cognitive deficits. Most notably, she identified therapeutic strategies able to both prevent and restore lost cognition. She received the Bridging the Gap Award from the California Institute for Quantitative Biosciences, the Innovation Award from the Weill Institute for Neurosciences. She serves as PI on NIH (NIA, NINDS and NCI) funded grants, a NASA grant and she also serves as a standing member of the Molecular Neurogenetic study section at the National Institutes of Health and Associate Editor for the Journal of Neuroinflammation.

  • The Johns Hopkins University, USA
  • Title: Imaging Neurovascular Abnormalities in Neurodegenerative Diseases
  • Time :

Abstract
Energy metabolism is crucial for maintenance of normal brain functions. As the supply of adequate oxygen and energy substrates for local metabolic demands is controlled by blood vessels in the brain, neurovascular abnormalities
may contribute to the neuropathology and functional deficits in brain diseases. Here, I will discuss our work on the investigation of microvascular and metabolic abnormalities in neurodegenerative diseases measured by advanced
MRI technologies developed at ultra-high magnetic field.

Biography
Dr. Hua is an Associate Professor in the F.M. Kirby Research Center for Functional Brain Imaging at Kennedy
Krieger Institute, and the Russell H. Morgan Department of Radiology at Johns Hopkins University. Dr. Hua’s research has centered on the development of novel MRI technologies for in vivo functional and physiological imaging in the brain, and the application of such methods for studies in healthy and diseased brains. These include the development of human and animal MRI methods to measure functional brain activities, cerebral perfusion and oxygen metabolism at high (3 Tesla) and ultra-high (7 Tesla and above) magnetic fields. He is particularly
interested in novel MRI approaches to image small blood and lymphatic vessels in the brain. Collaborating with clinical investigators, these techniques have been applied 1) to detect functional, vascular and metabolic abnormalities in the brain in neurodegenerative diseases such as Huntingdon’s disease (HD), Parkinson’s disease (PD), Alzheimer’s disease (AD) and mental disorders such as schizophrenia; and 2) to map brain functions
and cerebrovascular reactivity for presurgical planning in patients with vascular malformations, brain tumors and epilepsy.

  • Neuro-Horizon Pharma, USA
  • Title:Drug Development for the Treatment of Amyotrophic Lateral Sclerosis
  • Time :

Abstract
We have previously identified the interaction between mammalian V-ATPase a2-subunit isoform and cytohesin-2 (CTH2) and studied molecular details of binding between these proteins. In particular, we found that six peptides derived from the N-terminal cytosolic domain of a2-subunit (a2N1–402) are involved in the interaction with CTH2 [1]. However, the actual 3D binding interface was not determined in that study due to the lack of high-resolution structural information about a-subunits of V-ATPase. Here, using a combination of homology modeling and NMR analysis, we generated the structural model of complete a2N1–402 and uncovered the CTH2-binding interface. First, using the crystal structure of the bacterial M. rubber Icyt-subunit of A-ATPase as a template [2], we built a homology model of mammalian a2N1–352 fragment. Next, we combined it with the determined NMR structures of peptides a2N368–395 and a2N386–402 of the C-terminal section of a2N1–402. The complete molecular model of a2N1–402 revealed that six CTH2 interacting peptides are clustered in the distal and proximal lobe sub-domains of a2N1–402, showing that a2-subunit of V-ATPase interacts with two molecules of CTH2. Indeed, using Sec7/Arf-GEF activity assay we experimentally confirmed our model. These data are critical for drug development using: i) in silico computer-aided drug design (CADD) and ii) TR-FRET based high throughput screening (HTS) of the libraries of BBB-permeable small molecules [3,4]. In particular, it was shown that CTH2 interacts with mutant superoxide dismutase 1 (SOD1), a known cause of familial amyotrophic lateral sclerosis (ALS) [5]. Inhibition of CTH2 activity by small molecules protects against ER stress, enhances autophagic flux and reduces the burden of misfolded SOD1. These data indicate that targeting of cytohesins by peptides and/or small molecules in motor neurons may be beneficial for the treatment of ALS.

  • University of Nebraska, USA
  • Title:Neuron Model with Conductance-Resistance Symmetry
  • Time :

Abstract

We will derive a mathematical model for neuron by imposing only a principle of symmetry that two modelers must obtain the same model when one models the conductances of neural channels and the other models the channels’ resistances. Conductance-voltage characteristics for ion transport channels and protein gating channels are both derived. They are expressed as products of maximal conductances and opening probabilities for both types of channel. It gives an explanation to the critical role of spontaneous firing of individual channel pores and to the origin of leak current. The model has a better fit to a classical data than the Hodgkin-Huxley model does. It can also be reduced to a 2-dimensional model qualitatively similar to the FitzHugh-Nagumo equation and be expanded to a model of three ion channels capable of spike bursts. It gives an electrical circuit design for true artificial neuron. The channel opening probability function derived can also be used in the area of AI.

Biography

Dr. Bo Deng is a mathematician working in the field of Mathematical Biology. He obtained his PhD from Michigan State University in US. He has been a professor in the Department of Mathematics, University of Nebraska – Lincoln, US, since 1988. He has done researches in a few areas of Mathematical Biology, including Evolutionary Genetics, Population Genetics, Bioinformatics, Neurosciences, Evolutionary Ecology, and Community Ecology. He has also published works in the areas of Dynamical Systems, Bifurcation Theory, and Chaos Theory.

  • Nara Medical University Hospital, Japan
  • Title:Searching for Baby-Friendly Phototherapy to prevent Bilirubin Encephalopathy in Premature Infants
  • Time :

Abstract

Kernicterus (bilirubin encephalopathy), a neurological complication of neonatal hyperbilirubinemia, has been reported, especially in preterm infants, and neonatal hyperbilirubinemia management remains an important issue for neonatal care. Premature infants in severe jaundice often do not have the typical kernicterus symptoms shown, and in infancy, present with hearing loss and athetoid cerebral palsy. Needless to say, phototherapy is a treatment method for neonatal hyperbilirubinemia that has spread worldwide. There is a tendency to think that phototherapy has no adverse events other than effects on the retina. However, according to Morris et al, aggressive phototherapy for extremity very low birth weight infants did not change mortality or the incidence of neurological sequelae. On the contrary, the mortality rate increased for neonates with a birth weight of 500-750 g (Morris BH, et al. N Engl J Med.359, 2008). For this reason, phototherapy is not necessarily a safe treatment. Since 2010, we have conducted clinical studies on neonatal jaundice and animal studies using young rats with jaundice models. As a result, green light has an advantage in reducing photo-oxidative stress response, but blue wavelength is essential to reduce blood bilirubin. (Uchida Y, et al. Early Hum Dev. 91, 2015).This result motivated the pursuit of what would be an effective and harmless treatment to excrete bilirubin more quickly. Under the current management of jaundice, the decision to start or stop treatment is based on blood total bilirubin and unbound bilirubin levels, and bilirubin excretion has not been directly evaluated. In newborns only a few days old, especially preterm infants, liver enzymes and circulation are immature. In addition, bilirubin excreted in the intestinal tract is absorbed into the blood again by the entero-hepatic circulation, so that it is insufficient to evaluate the phototherapy effect used for jaundice treatment only by the blood bilirubin value. That is, the effect of reducing blood bilirubin in a short period of time with phototherapy is presumed to be excreted as a photo-isomer in urine, but currently it can only be detected by a special analysis method such as high-performance liquid chromatography (HPLC). That is, it is difficult to easily measure urinary bilirubin excretion immediately at the bedside. I would also like to mention at this meeting our ongoing work to establish a new method to assess urinary bilirubin excretion using the fluorescent protein UnaG, which binds specifically and strongly to unconjugated bilirubin.

Biography

Dr. Yumiko Uchida is a lecturer of division of neonatal intensive care, maternal, fetal and neonatal medical center, Nara Medical University Hospital. She graduated from Nara Medical University in 1995 and majored in Pediatrics at Nara Medical University Hospital. She has been engaged in neonatal intensive care since 1996. She has been studying neonatal hyperbilirubinemia in the last 10 years.

X