Blood glucose and β-hydroxybutyrate predict significant brain injury after hypoxia-ischemia in neonatal mice.

Background: The Vannucci procedure is widely used to model cerebral hypoxic-ischemic (HI) injury in neonatal rodents. Identifying minimally invasive biomarkers linked to brain injury would improve stratification of pups to experimental treatments. We hypothesized that extreme blood glucose (BG) and β-hydroxybutyrate (bHB) levels immediately after HI will correlate with severity of brain injury in this model.

The Vannucci Model of Hypoxic-Ischemic Injury in the Neonatal Rodent: 40 years Later.

Perinatal hypoxic-ischemic (HI) brain damage has long been a major cause of acute mortality and chronic neurological morbidity in infants and children. Experimental animal models are essential to gain insights into the pathogenesis and management of perinatal HI brain damage. Prior to 1980, only large animal models were available.

Cerebral asymmetry during development using linear measures from MRI.

Asymmetry of the human brain is a well-known phenomenon, but the nature and extent of these differences throughout postnatal development have not been examined. Accordingly, linear measurements of the brains of 121 infants, children, and adolescents were determined to ascertain cerebral hemispheric asymmetries. Using multiple statistical methods, the results showed that: 1) the frontal lobe is wider on the right, while the occipital lobe is wider on the left; 2) there are no side to side differences in cerebral hemispheric length or height; and 3) there are no major sex differences.

Assessing Cerebral Metabolism in the Immature Rodent: From Extracts to Real-Time Assessments.

Brain development is an energy-expensive process. Although glucose is irreplaceable, the developing brain utilizes a variety of substrates such as lactate and the ketone bodies, β-hydroxybutyrate and acetoacetate, to produce energy and synthesize the structural components necessary for cerebral maturation. When oxygen and nutrient supplies to the brain are restricted, as in neonatal hypoxia-ischemia (HI), cerebral energy metabolism undergoes alterations in substrate use to preserve the production of adenosine triphosphate.

Brain growth in modern humans using multiple developmental databases.

Objective: Currently, there are several published articles detailing brain growth in modern humans. The contained databases were derived using disparate methodologies. The objective of the present investigation was to determine the level of agreement among several collections of immature modern human brains.

Deactivation of mitochondrial complex I after hypoxia-ischemia in the immature brain.

Mortality from perinatal hypoxic-ischemic (HI) brain injury reached 1.15 million worldwide in 2010 and is also a major factor for neurological disability in infants. HI directly influences the oxidative phosphorylation enzyme complexes in mitochondria, but the exact mechanism of HI-reoxygenation response in brain remains largely unresolved.

The effects of adding prophylactic phenobarbital to therapeutic hypothermia in the term-equivalent hypoxic-ischemic rat.

BackgroundHypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Therapeutic hypothermia (TH) is the only available intervention, but neuroprotection is incomplete and variable. Seizures are common in infants with HIE undergoing TH and may worsen outcome.

Development of the Corpus Callosum: An MRI Study.

The size and shape of the corpus callosum and its major components (genu, body, and splenium) were measured by magnetic resonance imaging (MRI) in 118 normocephalic individuals aged from 1 postnatal week to 18.7 years. Genu, body, splenial, and total corpus callosal areas increased by 40-100% during the first year of life (p < 0.

In vivo Monitoring of Cerebral Hemodynamics in the Immature Rat: Effects of Hypoxia-Ischemia and Hypothermia.

Background: Neonatal hypoxic-ischemic (HI) encephalopathy occurs in 1-4 per 1,000 live term births and can cause devastating neurodevelopmental disabilities. Currently, therapeutic hypothermia (TH) is the only treatment with proven efficacy. Since TH is associated with decreased cerebral metabolism and cerebral blood flow (CBF), it is important to assess CBF at the bedside.

Therapeutic hypothermia and hypoxia-ischemia in the term-equivalent neonatal rat: characterization of a translational preclinical model.

Background: Hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity in survivors. Therapeutic hypothermia (TH) is the only available intervention, but the protection is incomplete. Preclinical studies of HIE/TH in the rodent have relied on the postnatal day (P) 7 rat whose brain approximates a 32-36 wk gestation infant, less relevant for these studies.

The role of inflammation in perinatal brain injury.

Inflammation is increasingly recognized as being a critical contributor to both normal development and injury outcome in the immature brain. The focus of this Review is to highlight important differences in innate and adaptive immunity in immature versus adult brain, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development. Perinatal brain injury can result from neonatal encephalopathy and perinatal arterial ischaemic stroke, usually at term, but also in preterm infants.

Neonatal encephalopathy: pre-clinical studies in neuroprotection.

Neonatal encephalopathy resulting from HI (hypoxia-ischaemia) continues to be a significant cause of mortality and morbidity in infants and children, affecting 1-2/1000 live term births and up to 60% of pre-term births. In order to understand the pathophysiology of this insult, as well as design therapeutic interventions, it is important to establish a relevant animal model for pre-clinical studies. One of the most frequently used models of HI-induced brain damage in immature animals is the unilateral carotid ligation/hypoxia model, initially developed in our laboratory more than 30 years ago.

Mast cell isolation from the immature rat brain.

Mast cells are immune cells of hematopoietic origin that circulate as precursor cells prior to migration into vascularized tissues where they mature and undergo terminal differentiation in response to different cytokines within the local environment. Mast cells are well known as important regulators of inflammatory processes in peripheral tissues and recent studies support the involvement of mast cells in mediating the inflammatory response to cerebral hypoxia-ischemia in both the neonatal and adult brain. To better study mast cell function in vivo, it is important to be able to identify their environment-specific phenotype, as well as to study their interaction with other neural cells in vitro.

N-3 fatty acid rich triglyceride emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice.

We questioned if acute administration of n-3 fatty acids (FA) carried in n-3 rich triglyceride (TG) emulsions provides neuroprotection in neonatal mice subjected to hypoxic-ischemic (H/I) brain injury. We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/I. H/I insult was induced in C57BL/6J 10-day-old mice by right carotid artery ligation followed by exposure to 8% O(2) for 15 minutes at 37°C.

A novel approach to the study of hypoxia-ischemia-induced clinical and subclinical seizures in the neonatal rat.

Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of acute mortality and chronic neurologic morbidity in infants and children. HIE is the most common cause of neonatal seizures, and seizure activity in neonates can be clinical, with both EEG and behavioral symptoms, subclinical with only EEG activity, or just behavioral. The accurate detection of these different seizure manifestations and the extent to which they differ in their effects on the neonatal brain continues to be a concern in neonatal medicine.

Craniometric measures of microcephaly using MRI.

Background: Microcephalic brains exhibit varying sizes, shapes, and dimensions when compared to normocephalic counterparts, but the extent of these differences is unresolved.

Aims: To ascertain developmental changes in brain morphology using craniometric (linear brain) measures derived from MRI in microcephalic individuals and in normocephalic controls.

Study Design: A retrospective, cross-sectional cohort study.

Pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties.

Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I (hypoxia-ischaemia) injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preconditioning stimulus would activate an adaptive astrocytic response. We analysed several functional parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O2).

Temporal changes in mRNA expression of the brain nutrient transporters in the lithium-pilocarpine model of epilepsy in the immature and adult rat.

The lithium-pilocarpine model mimics most features of human temporal lobe epilepsy. Following our prior studies of cerebral metabolic changes, here we explored the expression of transporters for glucose (GLUT1 and GLUT3) and monocarboxylates (MCT1 and MCT2) during and after status epilepticus (SE) induced by lithium-pilocarpine in PN10, PN21, and adult rats. In situ hybridization was used to study the expression of transporter mRNAs during the acute phase (1, 4, 12 and 24h of SE), the latent phase, and the early and late chronic phases.

Craniometric measures during development using MRI.

Developmental changes in brain volume and shape in infants, children, and adolescents were ascertained with MRI, using craniometric (linear brain) measures in 118 individuals, ages 1 postnatal week to 18.7years. Collected clinical data included age, sex, weight, height, body mass index, occipito-frontal circumference (OFC), and diagnosis prompting the MRI scan.

Response to 'comment on recent modeling studies of astrocyte-neuron metabolic interactions': much ado about nothing.

For many years, a tenet of cerebral metabolism held that glucose was the obligate energy substrate of the mammalian brain and that neuronal oxidative metabolism represented the majority of this glucose utilization. In 1994, Pellerin and Magistretti formulated the astrocyte-neuron lactate shuttle (ANLS) hypothesis, in which astrocytes, not neurons, metabolized glucose, with subsequent transport of the glycolytically derived lactate to fuel the energy needs of the neuron during neurotransmission. By considering the concentrations and kinetic characteristics of the nutrient transporter proteins, Simpson et al later supported the opposite view, in which lactate flows from neurons to astrocytes, thus leading to the neuron-astrocyte lactate shuttle (NALS).

An uncommon clinical condition: chronic thrombosis of the inferior vena cava. A case report and review of literature.

The lifetime incidence of deep vein thrombosis (DVT) is approximately 0.1% in general population and even more uncommon in subjects below 40 years of age. Thrombosis of the inferior vena cava (IVC) is an exceptionally rare clinical condition, with etiological factors similar to lower limb DVT.

Complement component c1q mediates mitochondria-driven oxidative stress in neonatal hypoxic-ischemic brain injury.

Hypoxic-ischemic (HI) brain injury in infants is a leading cause of lifelong disability. We report a novel pathway mediating oxidative brain injury after hypoxia-ischemia in which C1q plays a central role. Neonatal mice incapable of classical or terminal complement activation because of C1q or C6 deficiency or pharmacologically inhibited assembly of membrane attack complex were subjected to hypoxia-ischemia.

Moderate recurrent hypoglycemia during early development leads to persistent changes in affective behavior in the rat.

Recurrent hypoglycemia is a common problem among infants and children that is associated with several metabolic disorders and insulin-dependent diabetes mellitus. Although studies have reported a relationship between a history of juvenile hypoglycemia and psychological health problems, the direct effects of recurrent moderate hypoglycemia have not been fully determined. Thus, in this study, we used an animal model to examine the effects of recurrent hypoglycemia during the juvenile period on affective, social, and motor function (assessed under euglycemic conditions) across development.

The PPAR-gamma agonist, darglitazone, restores acute inflammatory responses to cerebral hypoxia-ischemia in the diabetic ob/ob mouse.

Diabetes is an increased risk factor for stroke and results in increased brain damage in experimental animals and humans. The precise mechanisms are unclear, but our earlier studies in the db/db mice suggested that the cerebral inflammatory response initiating recovery was both delayed and diminished in the diabetic mice compared with the nondiabetic db/+ mice. In this study, we investigated the actions of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist darglitazone in treating diabetes and promoting recovery after a hypoxic-ischemic (H/I) insult in the diabetic ob/ob mouse.