Mesial temporal lobe epilepsy (MTLE) is associated with high rates of depression and anxiety. A bidirectional causal relationship has been suggested, with these psychiatric comorbidities themselves enhancing epileptogenesis, possibly via hypercortisolemia. We examined the effects on epileptogenesis of chronic supplementation with low-dose corticosterone (CS) in the electrical amygdala kindling rat model.
View Article and Find Full Text PDFThis study examines the effects of a chronic prenatal insult on both the expression of brain-derived neurotrophic factor (BDNF) and TrkB proteins and the structural development of the fetal hippocampus and cerebellum. Chronic placental insufficiency (CPI) was induced via unilateral ligation of the uterine artery from midgestation to near term in the pregnant guinea pig. Fetuses were delivered at 60 days of gestation (dg, term approximately 67 dg) and classified as control or growth-restricted (GR) according to established criteria.
View Article and Find Full Text PDFNonhuman primate species have been selectively used in the scientific investigation of adult and newborn neurological diseases. The rhesus monkey has been utilized in models of term asphyxial insults, accurately reflecting the mechanisms and neuropathology demonstrated in the newborn human infant. More recently, a premature baboon model developed for evaluation of bronchopulmonary dysplasia has been applied to the investigation of cerebral development and injury, revealing high similarity in neuropathology to the premature human infant.
View Article and Find Full Text PDFObjectives: Mutations in the genes encoding the transcription factors PROP1 and POUF-1 (Pit-1) have been reported as common causes of combined pituitary hormone deficiency (CPHD), and HESX1 mutations have been identified in children with septo-optic dysplasia (SOD). There are few data on UK children. We have performed mutation analysis in a large cohort of affected children within the West Midlands region to assess the feasibility of a screening strategy for molecular diagnosis in CPHD and SOD.
View Article and Find Full Text PDFThe aim of the present study was to establish the neurochemical profile of amacrine and horizontal cells during ontogeny in the guinea pig, a precocial species where significant retinal development occurs prenatally as opposed to altricial species where development largely occurs postnatally. The expression of neurochemical markers of horizontal cells and specific amacrine cell populations was investigated from 20 days of gestation (dg, term approximately 67 dg) to adulthood. Amacrine cell populations were identified immunohistochemically using antibodies to gamma-amino-butyric acid, cholineacetyltransferase, calbindin, calretinin, neuronal nitric oxide synthetase and tyrosine hydroxylase; horizontal cells were labelled with calbindin.
View Article and Find Full Text PDFJ Neuropathol Exp Neurol
December 2004
Survivors of very premature birth face an increased risk of adverse motor, cognitive, and behavior sequelae. In order to understand the pathogenesis of these adverse outcomes, an animal model of premature birth and neonatal care in a species with a close similarity to the human infant is sought. In this histological and immunohistochemical study we have defined the pattern of cerebral injury in a premature baboon model undergoing similar neonatal intensive care to that of the human premature infant.
View Article and Find Full Text PDFPhilos Trans A Math Phys Eng Sci
January 2005
Coral reefs in the southwest Indian Ocean cover an area of ca. 18,530 km2 compared with a global reef area of nearly 300,000 km2. These regions are important as fishing grounds, tourist attractions and as a significant component of the global carbon cycle.
View Article and Find Full Text PDFJ Neuropathol Exp Neurol
November 2004
Chronic placental insufficiency (CPI) has the potential to affect fetal brain development and to cause brain injury. Our aim was to determine the effects of exposure to CPI during late gestation on brain and retinal structure and brain neurotrophin expression 8 weeks after birth. Six fetal sheep were exposed to CPI, induced by umbilico-placental embolization, from 120 days of gestation until term (approximately 147 days) such that fetal arterial oxygen saturation (SaO2) was reduced by approximately 50%.
View Article and Find Full Text PDFWhile research has focussed on the current and potential role of the practice nurse (PN) in Australia, the acceptability of this role by consumers has not been investigated. In 2002, two independent studies were carried out into consumer perceptions of PNs. A disscussion between the two groups of researchers at the inaugural National Pratice Nurse Conference in 2003, identifiied significant similarities in the findings of the tese studies.
View Article and Find Full Text PDFOur aim was to determine the effects of chronic placental insufficiency (CPI) during late gestation on the expression of neurotrophic factors and their receptors in the hippocampus and cerebellum in the near-term fetus. Structural alterations were also assessed in these brain regions. CPI was induced in eight fetal sheep by umbilicoplacental embolization (UPE) from 120 to 140 days of gestation (term approximately 147d) such that fetal arterial O2 saturation (SaO2) was maintained at approximately 50% of pre-UPE values.
View Article and Find Full Text PDFEvidence now suggests that compromised prenatal brain development may increase the risk for the manifestation of neurological disorders such as schizophrenia. We present a guinea-pig model which mimics a condition of human pregnancy, namely, chronic placental insufficiency. Previously we reported that at term there are changes in the brains of these offspring which are relevant to changes in patients with schizophrenia.
View Article and Find Full Text PDFObjective: The aim of this study was to determine the long-term effects of chronic placental insufficiency on the metabolic state and organ structure in the fetal and adolescent guinea pig.
Study Design: The maternal uterine artery was ligated at day 28-30 to reduce placental function and restrict fetal growth. Whole body and tissue weights and plasma metabolites were determined at 60 days of gestation and 8 weeks of age; tissue structure was determined at the latter age in restricted and control offspring.
It is well known that the hypothalamic-pituitary-adrenal (HPA) axis is activated during stress. Recent work suggests it is also implicated in the regulation of "normal" behaviors. The present studies investigated the effects of adrenalectomy and of varying glucocorticoid concentrations on adult maternal behavior in primiparous rats.
View Article and Find Full Text PDFJ Soc Gynecol Investig
September 2004
Objective: Previous studies on the effects of umbilical cord occlusion (UCO) on the fetal brain have focused on short-term alterations, and in most cases have used only subjective techniques to evaluate brain injury. Our aim was to assess quantitatively the persistent consequences of UCO on the developing brain; we also examined the retina.
Methods: We subjected fetal sheep to a single episode of UCO at 126 days of gestation (term approximately 147 days) to induce at least 10 minutes of isoelectric fetal electrocorticogram (ECoG).
Invest Ophthalmol Vis Sci
July 2004
Purpose: Very low birth weight (VLBW) and fetal growth restriction are associated with increased risks of long-term visual impairments, including alterations to contrast sensitivity, a parameter mediated in part by dopaminergic amacrine cells. This study was conducted to determine whether chronic placental insufficiency (CPI), sufficient to cause growth restriction, results in neurochemical alterations to retinal interneurons, specifically amacrine and horizontal cell populations near term.
Methods: CPI was induced just before midgestation (term approximately 67 days of gestation, dg) in guinea pigs through unilateral ligation of the uterine artery.
The intrauterine environment can significantly affect fetal brain development. Here we review our recent findings using animal models that mimic adverse intrauterine conditions which could exist during human pregnancy. We have focused on effects of both acute and chronic hypoxic and inflammatory insults.
View Article and Find Full Text PDFBackground And Objective: To investigate the clinical application of a mathematical model of pulmonary gas exchange, which ascribes hypoxaemia to shunt and ventilation/perfusion mismatch. Ventilation/perfusion mismatch is quantified by deltaPO2, which is the drop in oxygen pressure from alveoli to lung capillaries. Shunt and deltaPO2 were used to describe changes in oxygenation after coronary artery bypass grafting.
View Article and Find Full Text PDFAnnu Rev Pharmacol Toxicol
May 2004
The completion of the human genome sequencing project has identified approximately 720 genes that belong to the G-protein coupled receptor (GPCR) superfamily. Approximately half of these genes are thought to encode sensory receptors. Of the remaining 360 receptors, the natural ligand has been identified for approximately 210 receptors, leaving 150 so-called orphan GPCRs with no known ligand or function.
View Article and Find Full Text PDFThe interaction of proteins with hydroxyapatite (HAP), specifically proteoglycans and their spatial arms, glycosaminoglycans (GAGs) in addition to serum proteins, play an important role in regulating biological mineralisation. In this study, seeded HAP growth experiments revealed that inhibition of HAP formation by bovine serum albumin (BSA) was significantly elevated in combination with chondroitin 4-sulphate (C4S) versus BSA with heparin. Data suggest that C4S and BSA adsorb to different calcium sites on the HAP surface.
View Article and Find Full Text PDFPast animal studies of the performance-enhancing properties of stimulant drugs, such as caffeine, may have suffered from a number of procedural and ethical problems. For example. the housing condition of the animals was often not taken into consideration.
View Article and Find Full Text PDFThe efficacy of lofexidine/naloxone was compared with lofexidine/placebo in a double-blind, randomized, placebo-controlled trial in 89 opiate-dependent patients. There were no significant differences between the two groups in the proportion of patients completing detoxification or in the length of stay. Patients in the active naloxone group demonstrated gradual reductions in levels of withdrawal and craving over the detoxification period.
View Article and Find Full Text PDFObjective: Endotoxin causes hypoxemia and white matter injury in the preterm ovine fetus. Because cerebral hypoxia could contribute to brain injury, our objective was to determine the effects of endotoxin on regional cerebral oxygen (O(2)) delivery. To investigate causes of fetal hypoxemia, we also measured placental blood flow.
View Article and Find Full Text PDFIntrauterine infection has been associated with fetal brain injury and preterm birth. We have recently shown that repeated exposure to bacterial endotoxin leads to hypoxia and brain injury in the preterm ovine fetus and we considered it possible that endotoxin could also damage the placenta. Our aim therefore was to assess placental structure following repeated exposure to endotoxin.
View Article and Find Full Text PDFThe aim of this study was to determine the effects of foetal growth restriction on the retina after birth. Foetal growth restriction (FGR) was induced via umbilico-placental embolization (UPE) in ewes from 120 days of pregnancy until term (term approximately 147 days); controls were not exposed to UPE. Lambs were delivered and raised until 2 years of age when retinas were collected and processed for structural and neurochemical analysis.
View Article and Find Full Text PDFBackground: The Coventry Consensus in 1998 recommended a single height measurement of all children at school entry or around the age of 5 years and prompt referral of children with height <0.4th centile for further assessment, in order to identify undetected and treatable asymptomatic growth disorders.
Aim: To determine adherence and practicalities of following the Coventry Consensus recommendations in a community setting and the cost implications.