Fetal Brain Activity in the Sheep Model with Intrauterine Hypoxia
The fetal and early neonatal period is a time of rapid brain growth and development, dependent upon adequate oxygenation. Fetal hypoxia, whether chronic due to placental insufficiency or intermittent cord compression, or acute during labor, may give rise to aberrant development and neurologic sequelae. This chapter reviews the metabolic activities and behavioral states of the brain throughout the late fetal period, and the methods for studying them using the chronically instrumented ovine fetus. Also outlined are methods for studying hypoxia in the ovine fetus through embolization of the placenta, and occlusion of the umbi...
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

Models of Perinatal Brain Injury in Premature and Term Newborns Resulting from Gestational Inflammation Due to Inactivated Group B Streptococcus (GBS), or Lipopolysaccharide (LPS) from E. coli and/or Immediately Postnatal Hypoxia-Ischemia (HI)
It is known that gestational and/or perinatal inflammation combined or not with hypoxia-ischemia (HI) is a risk factor for brain injuries, but the mechanisms underlying are still unclear. This chapter discusses about animal models mimicking those conditions, allowing scientists to uncover mechanisms involved and to study the adverse effects on the offspring. Here is presented a model of maternal inflammation induced by inactivated Group B Streptococcus (Sect. 2) and two experimental designs using LPS. One explores the effects of prenatal LPS administration and/or immediately postnatal HI (Sect. 3) and the second one, the i...
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

Preterm Rabbit Model of Glycerol-Induced Intraventricular Hemorrhage
Intraventricular hemorrhage (IVH) remains a major complication of prematurity. We have developed a model of IVH in preterm rabbit pups. We deliver rabbit pups prematurely by C-section at 29-day gestational age (term = 32 days) and inject intraperitoneal glycerol at 3 h age to induce IVH. About 80 % of glycerol-treated pups develop IVH within 8 h age, which can be detected accurately with head ultrasound. These pups are reared in an infant incubator and gavage fed. At postnatal day 14, they exhibit hypomyelination, gliosis, and impaired neurological function. Hence, this is a novel animal model of IVH that can...
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

Perinatal Intracerebral Hemorrhage Model and Developmental Disability
Perinatal intracerebral hemorrhage, also known as germinal matrix hemorrhage (GMH), refers to the bleeding that arises from the sub-ependymal (or periventricular) germinal region of the immature brain. Intraventricular hemorrhage (IVH) refers to the bleeding that extends into the ventricles, usually as an extension of GMH. Clinical studies have shown that infants who experience GMH/IVH may develop hydrocephalus or suffer from long-term neurological dysfunctions, including cerebral palsy, seizures, and learning disabilities. Understanding the pathogenesis of subsequent brain damage is important for the prevention and manage...
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

Bilateral Uterine Artery Ligation (BUAL): Placental Insufficiency Causing Fetal Growth Restriction and Cerebral Palsy
Placental insufficiency is the leading cause of intrauterine growth restriction in the western world. The fetus, when exposed to a compromised environment, is vulnerable to a number of disorders later in life, as a consequence of the reduction in oxygen and nutrition during gestation and the resulting fetal growth restriction. These conditions include neurological disabilities such as cerebral palsy (CP), intellectual disability, epilepsy, and mental health issues in childhood (Autism and ADHD) and in later life (schizophrenia). Certainly, fetal growth restriction as a result of placental insufficiency has been strongly as...
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

Unilateral Common Carotid Artery Ligation as a Model of Perinatal Asphyxia: The Original Rice–Vannucci Model
Hypoxic-ischemic encephalopathy (HIE) is a detrimental event leading to unfavorable neurological outcomes in the newborn, the clinical phenotype of which is typically referred to as cerebral palsy. The high incidence of HIE results in a need for animal models that can replicate this human experience in order to determine the pathophysiology of injury and develop therapeutic interventions. One of the first models to be developed was, the now commonly referred to as the Rice–Vannucci model, after the student and principle investigator who first developed and described the model. Now, perhaps the best characterized and ...
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

The Effect of Age on Brain Plasticity in Animal Models of Developmental Disability
Brain development is a complex interaction of environmental experiences and genetic influences. Experiences include both prenatal (gestational), perinatal, and later events including stress, gonadal hormones, drugs (prescription and others), sensory stimulation (e.g., tactile stimulation), and sensory deprivation. By manipulating these factors it is possible to get a better understanding of how brain and behavioral phenotypes emerge. Methods are outlined on how to study and assess these early experiences. (Source: Springer protocols feed by Neuroscience)
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

Animal Models of Cerebral Dysgenesis: Excitotoxic Brain Injury
Brain damage through excitotoxic mechanisms is a major cause of pediatric neurologic diseases. These include hypoxic-ischemic encephalopathy, periventricular white matter damage (PWMD), stroke, meningoencephalitis, traumatic brain injury, and neurodegenerative disorders. In the present chapter, we describe the procedure to generate a model of excitotoxic injury by intra-cerebrally injecting glutamate analogues. This model provides tools for investigating excitotoxic influences at various stages of neural development and for identifying protective substances against excitotoxicity. (Source: Springer protocols feed by Neuroscience)
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

Modeling Intellectual Disability in Drosophila
We present here a model of learning and memory in Drosophila that has now been used by several groups to gain genetic understanding in memory defects related to ID genes. We review the pertinent background about the assay and its relation to ID. We also review the assay in detail and provide some advice about troubleshooting tips. Finally, we discuss how flies and other animal models could be used synergistically to develop new treatment for ID patients. (Source: Springer protocols feed by Neuroscience)
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

Animal Models of Fetal Alcohol Spectrum Disorder
This chapter reviews the development and use of animal models in research on Fetal Alcohol Spectrum Disorder, highlighting methodological issues. The development of suitable animal models in this field has been crucial in investigating the wide range of effects of prenatal alcohol exposure under tightly controlled conditions, as well as factors that can influence the severity of effects observed, and the mechanisms mediating those effects. Animal models in this field have been critical in demonstrating that alcohol is a powerful teratogen with serious neurodevelopmental consequences, a fact that was met with skepticism by ...
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

The Newborn Pig Global Hypoxic-Ischemic Model of Perinatal Brain and Organ Injury
Hypoxic-ischemic encephalopathy (HIE) remains an important cause of neonatal death and is a major contributor of disability. Animal models have contributed greatly to the understanding of the pathophysiology of HIE such as the mode of cell death, secondary energy failure, and the development of therapeutic interventions such as therapeutic hypothermia. Further research into the understanding of pathophysiology of HIE and neuroprotective interventions is required. The newborn pig global hypoxic-ischemic model of perinatal brain and organ injury is a valuable model simulating neonatal encephalopathy secondary to perinatal as...
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

Physiologic Aspects of the Piglet as a Model of Neonatal Hypoxia and Reoxygenation
Every year, there are approximately one million newborns die because of birth asphyxia. For those who survive, they have an increased risk for adverse neurodevelopmental outcomes due to the insult. Newborn piglets are a useful model for hypoxia-ischemic encephalopathy injury in human newborns. We here describe a swine model of neonatal hypoxia and reoxygenation, the instrumentation procedures and hypoxia-reoxygenation protocol. The model allows observation of physiological changes of systemic and regional circulations including the cerebral perfusion, as well as biochemical and histological studies of hypoxia-reoxygenation...
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

A Newborn Piglet Survival Model of Post-hemorrhagic Ventricular Dilatation (PHVD)
Intra-ventricular hemorrhage (IVH) and post-hemorrhagic ventricular dilatation (PHVD) are important issues in neonatal care and continue to contribute to significant motor and cognitive morbidity. Several questions about its pathophysiology remain unanswered and animal models have been useful in identifying relevant risk factors and potential mechanisms. In this chapter, we describe a neonatal piglet model of IVH and PHVD involving the injection of homologous blood with an elevated hematocrit into the ventricular system. The animals are capable of long-term survival and, through a ventricular access device inserted in the ...
Source: Springer protocols feed by Neuroscience - September 21, 2015 Category: Neuroscience Source Type: news

Computing Conformational Free Energies of iGluR Ligand-Binding Domains
Ionotropic glutamate receptors (iGluRs) transduce chemical signals at synapses into electrical impulses. This function relies on concerted conformational changes that are propagated among the linked domains of the tetrameric protein assembly making up each receptor. A key conformational change is the closure of the ligand-binding domain (LBD) upon agonist binding, which eventually gates the transmembrane ion channel domain. The free energy that becomes available for gating transitions is governed by the LBD free energy landscapes for apo and ligand-bound states. These landscapes describe the thermodynamic equilibrium among...
Source: Springer protocols feed by Neuroscience - September 16, 2015 Category: Neuroscience Source Type: news

NMR Approaches to Functional Dynamics of Genetically Separated iGluR Domains
We describe here the production and isotopic labeling of the ligand-binding domain of an AMPA receptor (GluA2) to permit studies of protein dynamics by NMR. The strategies for resonance assignment and the experiments used to study dynamics are also described. (Source: Springer protocols feed by Neuroscience)
Source: Springer protocols feed by Neuroscience - September 16, 2015 Category: Neuroscience Source Type: news