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Insult
Kinds of Insult Selected AbstractsMagnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 7ALCOHOLISM, Issue 1 2010Elizabeth A. Godin Background:, This magnetic resonance microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment. The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects. Methods:, C57Bl/6J female mice were intraperitoneally (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at either 7.0 Tesla (T) or 9.4 T. Resulting 29 ,m isotropic spatial resolution scans were segmented and reconstructed to provide 3D images. Linear and volumetric brain measures, as well as morphological features, were compared for control and ethanol-exposed fetuses. Following MRM, selected specimens were processed for routine histology and light microscopic examination. Results:, Gestational day 7 ethanol exposure resulted in a spectrum of median facial and forebrain deficiencies, as expected. This range of abnormalities falls within the HPE spectrum; a spectrum for which facial dysmorphology is consistent with and typically is predictive of that of the forebrain. In addition, other defects including median facial cleft, cleft palate, micrognathia, pituitary agenesis, and third ventricular dilatation were identified. MRM analyses also revealed cerebral cortical dysplasia/heterotopias resulting from this acute, early insult and facilitated a subsequent focused histological investigation of these defects. Conclusions:, Individual MRM scans and 3D reconstructions of fetal mouse brains have facilitated demonstration of a broad range of GD 7 ethanol-induced morphological abnormality. These results, including the discovery of cerebral cortical heterotopias, elucidate the teratogenic potential of ethanol insult during the third week of human prenatal development. [source] Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 8ALCOHOLISM, Issue 6 2009Scott E. Parnell Background:, Magnetic resonance microscopy (MRM), magnetic resonance imaging (MRI) at microscopic levels, provides unprecedented opportunities to aid in defining the full spectrum of ethanol's insult to the developing brain. This is the first in a series of reports that, collectively, will provide an MRM-based atlas of developmental stage-dependent structural brain abnormalities in a Fetal Alcohol Spectrum Disorders (FASD) mouse model. The ethanol exposure time and developmental stage examined for this report is gestational day (GD) 8 in mice, when the embryos are at early neurulation stages; stages present in humans early in the fourth week postfertilization. Methods:, For this study, pregnant C57Bl/6J mice were administered an ethanol dosage of 2.8 g/kg intraperitoneally at 8 days, 0 hour and again at 8 days, 4 hours postfertilization. On GD 17, fetuses that were selected for MRM analyses were immersion fixed in a Bouin's/Prohance® solution. Control fetuses from vehicle-treated dams were stage-matched to those that were ethanol-exposed. The fetal mice were scanned ex vivo at 7.0 T and 512 × 512 × 1024 image arrays were acquired using 3-D spin warp encoding. The resulting 29 ,m (isotropic) resolution images were processed using ITK-SNAP, a 3-D segmentation/visualization tool. Linear and volume measurements were determined for selected brain, head, and body regions of each specimen. Comparisons were made between control and treated fetuses, with an emphasis on determining (dis)proportionate changes in specific brain regions. Results:, As compared with controls, the crown-rump lengths of stage-matched ethanol-exposed GD 17 fetuses were significantly reduced, as were brain and whole body volumes. Volume reductions were notable in every brain region examined, with the exception of the pituitary and septal region, and were accompanied by increased ventricular volumes. Disproportionate regional brain volume reductions were most marked on the right side and were significant for the olfactory bulb, hippocampus, and cerebellum; the latter being the most severely affected. Additionally, the septal region and the pituitary were disproportionately large. Linear measures were consistent with those of volume. Other dysmorphologic features noted in the MR scans were choanal stenosis and optic nerve coloboma. Conclusions:, This study demonstrates that exposure to ethanol occurring in mice at stages corresponding to the human fourth week postfertilization results in structural brain abnormalities that are readily identifiable at fetal stages of development. In addition to illustrating the utility of MR microscopy for analysis of an FASD mouse model, this work provides new information that confirms and extends human clinical observations. It also provides a framework for comparison of structural brain abnormalities resulting from ethanol exposure at other developmental stages and dosages. [source] Adding Insult to Injury: Nancy Fraser Debates Her Critics , Edited by Kevin OlsenTHE BRITISH JOURNAL OF SOCIOLOGY, Issue 4 2009George Lawson No abstract is available for this article. [source] Molecular Changes in Normal Appearing White Matter in Multiple Sclerosis are Characteristic of Neuroprotective Mechanisms Against Hypoxic InsultBRAIN PATHOLOGY, Issue 4 2003Ursula Graumann Multiple sclerosis is a chronic inflammatory disease of the CNS leading to focal destruction of myelin, still the earliest changes that lead to lesion formation are not known. We have studied the geneexpression pattern of 12 samples of normal appearing white matter from 10 post-mortem MS brains. Microarray analysis revealed upregulation of genes involved in maintenance of cellular homeostasis, and in neural protective mechanisms known to be induced upon ischemic preconditioning. This is best illustrated by the upregulation of the transcription factors such as HIF-1, and associated PI3K/Akt signalling pathways, as well as the upregulation of their target genes such as VEGF receptor 1. In addition, a general neuroprotective reaction against oxidative stress is suggested. These molecular changes might reflect an adaptation of cells to the chronic progressive pathophysiology of MS. Alternatively, they might also indicate the activation of neural protective mechanisms allowing preservation of cellular and functional properties of the CNS. Our data introduce novel concepts of the molecular pathogenesis of MS with ischemic preconditioning as a major mechanism for neuroprotection. An increased understanding of the underlying mechanisms may lead to the development of new more specific treatment to protect resident cells and thus minimize progressive oligondendrocyte and axonal loss. [source] Postoperative troponin I values: Insult or injury?CLINICAL CARDIOLOGY, Issue 10 2000Keith A. Horvath M.D. Abstract Background: Troponin I (TnI) is increasingly employed as a highly specific marker of acute myocardial ischemia. The value of this marker after cardiac surgery is unclear. Hypothesis: The purpose of this study was to measure serum TnI levels prospectively at 1, 6, and 72 h after elective cardiac operations. In addition, TnI levels were measured from the shed mediastinal blood at 1 and 6 h postoperatively. Serum values were correlated with cross clamp time, type of operation, incidence of perioperative myocardial infarction, as assessed by postoperative electrocardiograms (ECG) and regional wall motion, as documented by intraoperative transesophageal echocardiography (TEE). Methods: Sixty patients underwent the following types of surgery: coronary artery bypass graft (CABG) (n = 45), valve repair/replacement (n = 10), and combination valve and coronary surgery (n = 5). Myocardial protection consisted of moderate systemic hypothermia (30,32°C), cold blood cardioplegia, and topical cooling for all patients. Results: Of 60 patients, 57 (95%) had elevated TnI levels, consistent with myocardial injury, 1 h postoperatively. This incidence increased to 98% (59/60) at 6 h postoperatively. There was a positive correlation between the length of cross clamp time and initial postoperative serum TnI (r = 0.70). There was no difference in the serum TnI values whether or not surgery was for ischemic heart disease (CABG or CABG + valve versus valve). There were no postoperative myocardial infarctions as assessed by serial ECGs. There was no evidence of diminished regional wall motion by TEE. Levels of TnI in the mediastinal shed blood were greater than assay in 58% (35/60) of the patients at 1 h and in 88% (53/60) at 6 h postoperatively. Patients who received an auto-transfusion of mediastinal shed blood (n = 22) had on average a 10-fold postoperative increase in serum TnI levels between 1 and 6 h. Patients who did not receive autotransfusion average less than doubled their TnI levels over the same interval. At 72 h, TnI levels were below the initial postoperative levels but still indicative of myocardial injury. Conclusion: Postoperative TnI levels are elevated after all types of cardiac surgery. There is a strong correlation between intraoperative ischemic time and postoperative TnI level. Further elevation of TnI is significantly enhanced by reinfusion of mediastinal shed blood. Despite these postoperative increases in TnI, there was no evidence of myocardial infarction by ECG or TEE. The postoperative TnI value is even less meaningful after autotransfusion of shed mediastinal blood. [source] Modulation of ongoing cognitive processes by emotionally intense wordsPSYCHOPHYSIOLOGY, Issue 2 2008Luis Carretié Abstract Contrary to what occurs with negative pictures, negative words are, in general, not capable of interfering with performance in ongoing cognitive tasks in normal subjects. A probable explanation is the limited arousing power of linguistic material. Especially intense words (insults and compliments), neutral personal adjectives, and pseudowords were presented to 28 participants while they executed a lexical decision task. Insults were associated with the poorest performance in the task and compliments with the best. Amplitude of the late positive component of the event-related potentials, originating at parietal areas, was maximal in response to compliments and insults, but latencies were delayed in response to the latter. Results suggest that intense emotional words modulate ongoing cognitive processes through both bottom-up (attentional capture by insults) and top-down (facilitation of cognitive processing by arousing words) mechanisms. [source] Force,frequency and force,length properties in skeletal muscle following unilateral focal ischaemic insult in a rat modelACTA PHYSIOLOGICA, Issue 3 2009G. N. Dormer Abstract Aim:, Our purpose was to quantify skeletal muscle properties following unilateral focal ischaemic insult (stroke) in a rat model. Methods:, Male rats were divided into two groups: stroke and 2 weeks recovery (n = 8) and control group (n = 7). Stroke was induced in the area of the motor neocortex containing hind limb corticospinal neurones. Contractile properties of the medial gastrocnemius muscle were measured in situ in both limbs. Force,length and force,frequency properties were measured before and 35 min after 5 min fatiguing stimulation. Results:, Stroke resulted in bilateral tetanic fade during 200 Hz stimulation. When normalized to 100 Hz contractions, force at 200 Hz was 95.4 ± 0.9% for the paretic muscles, 96.7 ± 1.7% for non-paretic muscles and 102.2 ± 1.0% for muscles of control rats (P = 0.006). Prior to fatiguing contractions, there was no difference in the length dependence of force. During repetitive contractions, active force fell significantly to 19 ± 4 and 25 ± 5% of initial force in paretic and non-paretic muscles of animals with a stroke respectively. In control animals active force fell to 37 ± 5%. During repetitive contractions, fusion index increased in muscles of stroke animals to 1.0 ± 0 but in control animals it was 0.95 ± 0.02. There was selective force depression at short lengths for fatigued paretic muscle (significant difference at muscle lengths less than reference length ,2 mm). Conclusion:, The tetanic fade at high stimulation frequencies indicates that there may be activation failure following focal ischaemic insult. The greater magnitude of fatigue and selective depression at short lengths following repetitive contractions should be investigated further. [source] Effect of combined supplementation with vitamin E and alpha-lipoic acid on myocardial performance during in vivo ischaemia-reperfusionACTA PHYSIOLOGICA, Issue 4 2000Coombes Reactive oxygen species (ROS) contribute significantly to myocardial ischaemia-reperfusion (I-R) injury. Recently the combination of the antioxidants vitamin E (VE) and alpha-lipoic acid (, -LA) has been reported to improve cardiac performance and reduce myocardial lipid peroxidation during in vitro I-R. The purpose of these experiments was to investigate the effects of VE and , -LA supplementation on cardiac performance, incidence of dysrhythmias and biochemical alterations during an in vivo myocardial I-R insult. Female Sprague,Dawley rats (4-months old) were assigned to one of the two dietary treatments: (1) control diet (CON) or (2) VE and , -LA supplementation (ANTIOXID). The CON diet was prepared to meet AIN-93M standards, which contains 75 IU VE kg,1 diet. The ANTIOXID diet contained 10 000 IU VE kg,1 diet and 1.65 g , -LA kg,1 diet. After the 14-week feeding period, significant differences (P < 0.05) existed in mean myocardial VE levels between dietary groups. Animals in each experimental group were subjected to an in vivo I-R protocol which included 25 min of left anterior coronary artery occlusion followed by 10 min of reperfusion. No group differences (P > 0.05) existed in cardiac performance (e.g. peak arterial pressure or ventricular work) or the incidence of ventricular dysrhythmias during the I-R protocol. Following I-R, two markers of lipid peroxidation were lower (P < 0.05) in the ANTIOXID animals compared with CON. These data indicate that dietary supplementation of the antioxidants, VE and , -LA do not influence cardiac performance or the incidence of dysrhythmias but do decrease lipid peroxidation during in vivo I-R in young adult rats. [source] Hypothermic insult to the periodontium: a model for the study of aseptic tooth resorptionDENTAL TRAUMATOLOGY, Issue 1 2000C. W. Dreyer Abstract , The aim of the current investigation was to define an animal model for the study of hard tissue resorption by examining the responses of the periodontal ligament (PDL) to both single and multiple episodes of hypothermic injury to the crowns of rat teeth. A group of 12 male rats weighing 200,250 g were anesthetized, and pellets of dry ice (CO2) were applied once to the crowns of the right first maxillary molars for continuous periods of 10 or 20 min. Animals were sacrificed at 2, 7, 14 and 28 days and tissues were processed for routine histological examination. A second group of eight animals and a third group of 12 animals were subjected to three applications of dry ice over a period of 1 week and sacrificed at 2 and 14 days respectively after the final application. In addition to thermal insult, the periodontium of teeth from a fourth group of six rats was subjected to mechanical trauma. Examination of the sections from the group undergoing a single freezing episode revealed that, by 1 week, shallow resorption lacunae had appeared on the root surface. These became more extensive after 14 days. At the same time hyaline degeneration was evident in the PDL. Within this group, teeth subjected to the longer 20-min application times generally showed more extensive injuries. By 28 days, evidence of repair was observed with reparative cementum beginning to line the resorption lacunae in the root dentin. Sections from animals subjected to multiple episodes of thermal trauma and those subjected to additional mechanical insult showed more extensive external root resorption than those from single-injury animals. It was concluded that low temperature stimuli applied to the crowns of rat molars were capable of eliciting a sterile degenerative response in the PDL which, in turn, resulted in external root resorption. Furthermore, the degree of this tissue injury was commensurate with the duration and number of exposures to the trauma. The results also indicated that progression of the resorptive process required periodic exposure to the injury, in the absence of which repair to the damaged root occurred. [source] Environmental complexity and central nervous system development and functionDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2004Mark H. Lewis Abstract Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching, neurogenesis, gene expression, and improved learning and memory. Moreover, in animal models of CNS insult (e.g., gene deletion), a more complex environment has attenuated or prevented the sequelae of the insult. Of relevance is the prevention of seizures and attenuation of their neuropathological sequelae as a consequence of exposure to a more complex environment. Relatively little attention, however, has been given to the issue of sensitive periods associated with such effects, the relative importance of social versus inanimate stimulation, or the unique contribution of exercise. Our studies have examined the effects of environmental complexity on the development of the restricted, repetitive behavior commonly observed in individuals with autism. In this model, a more complex environment substantially attenuates the development of the spontaneous and persistent stereotypies observed in deer mice reared in standard laboratory cages. Our findings support a sensitive period for such effects and suggest that early enrichment may have persistent neuroprotective effects after the animal is returned to a standard cage environment. Attenuation or prevention of repetitive behavior by environmental complexity was associated with increased neuronal metabolic activity, increased dendritic spine density, and elevated neurotrophin (BDNF) levels in brain regions that are part of cortical,basal ganglia circuitry. These effects were not observed in limbic areas such as the hippocampus. MRDD Research Reviews 2004;10:91,95. © 2004 Wiley-Liss, Inc. [source] Models of white matter injury: Comparison of infectious, hypoxic-ischemic, and excitotoxic insultsDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 1 2002Henrik Hagberg Abstract White matter damage (WMD) in preterm neonates is strongly associated with adverse outcome. The etiology of white matter injury is not known but clinical data suggest that ischemia-reperfusion and/or infection-inflammation are important factors. Furthermore, antenatal infection seems to be an important risk factor for brain injury in term infants. In order to explore the pathophysiological mechanisms of WMD and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, numerous novel animal models have been developed over the past decade. WMD can be induced by antenatal or postnatal administration of microbes (E. coli or Gardnerella vaginalis), virus (border disease virus) or bacterial products (lipopolysaccharide, LPS). Alternatively, various hypoperfusion paradigms or administration of excitatory amino acid receptor agonists (excitotoxicity models) can be used. Irrespective of which insult is utilized, the maturational age of the CNS and choice of species seem critical. Generally, lesions with similarity to human WMD, with respect to distribution and morphological characteristics, are easier to induce in gyrencephalic species (rabbits, dogs, cats and sheep) than in rodents. Recently, however, models have been developed in rats (PND 1,7), using either bilateral carotid occlusion or combined hypoxia-ischemia, that produce predominantly white matter lesions. LPS is the infectious agent most often used to produce WMD in immature dogs, cats, or fetal sheep. The mechanism whereby LPS induces brain injury is not completely understood but involves activation of toll-like receptor 4 on immune cells with initiation of a generalized inflammatory response resulting in systemic hypoglycemia, perturbation of coagulation, cerebral hypoperfusion, and activation of inflammatory cells in the CNS. LPS and umbilical cord occlusion both produce WMD with quite similar distribution in 65% gestational sheep. The morphological appearance is different, however, with a more pronounced infiltration of inflammatory cells into the brain and focal microglia/macrophage ("inflammatory WMD") in response to LPS compared to hypoperfusion evoking a more diffuse microglial response usually devoid of cellular infiltrates ("ischemic WMD"). Furthermore, low doses of LPS that by themselves have no adverse effects in 7-day-old rats (maturation corresponding to the near term human fetus), dramatically increase brain injury to a subsequent hypoxic-ischemic challenge, implicating that bacterial products can sensitize the immature CNS. Contrary to this finding, other bacterial agents like lipoteichoic acid were recently shown to induce tolerance of the immature brain suggesting that the innate immune system may respond differently to various ligands, which needs to be further explored. MRDD Research Reviews 2002;8:30,38. © 2002 Wiley-Liss, Inc. [source] Outcome of severe unilateral cerebellar hypoplasiaDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 8 2010ANDREA PORETTI Aim, Complete or subtotal absence of one cerebellar hemisphere is exceptional; only single cases have been described. We aimed to assess the long-term outcome in children with severe unilateral cerebellar hypoplasia (UCH). Method, As part of a retrospective study we describe neuroimaging features, clinical findings, and cognitive outcomes of seven children with UCH (five males, two females; age at first magnetic resonance imaging [MRI]: median 1y 3mo, range 9d,8y 10mo; age at latest follow-up: median 6y 6mo, range 2y 3mo,14y 11mo). Results, One child had abnormalities on prenatal MRI at 21 weeks' gestation. The left cerebellar hemisphere was affected in five children, and the right hemisphere in two children. The vermis was involved in five children. The volume of the posterior fossa was variable. At the latest follow-up, neurological findings included truncal ataxia and muscular hypotonia in five children, limb ataxia in three patients, and head nodding in two patients. Three children had learning disability*, five had speech and language disorders, and one had a severe behavioural disorder. Interpretation, Severe UCH is a residual change after a disruptive prenatal cerebellar insult, most likely haemorrhagic. The outcome is variable, ranging from almost normal development to marked developmental impairment. Ataxia is a frequent but not a leading sign. It seems that involvement of the cerebellar vermis is often, but not consistently, associated with a poorer cognitive outcome, whereas an intact vermis is associated with normal outcome and no truncal ataxia. [source] Stroke in the developing brain and intractable epilepsy: effect of timing on hippocampal sclerosisDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2003Waney Squier FRCP FRC Path A detailed study was made of the pathology of specimens removed by hemispherectomy for the treatment of intractable epilepsy in children with unilateral middle cerebral artery stroke. Neuropathological criteria were used to differentiate strokes that occurred in early intrauterine development (before 28 weeks gestational age) from those occurring in the last trimester, at birth, or after birth: 19 children had early strokes and 21 late. There was no difference in seizure history or occurrence of febrile convulsions in these two groups. Hippocampal tissue was available in 20 patients; pathology in the hippocampus, remote from the infarcted area, showed a marked difference between early-onset and late-onset groups. Hippocampal sclerosis was uncommon in children with early-onset strokes but developed in most of the children whose strokes were of later origin. However, hippocampal sclerosis was more closely related to a clinical history of a late initial precipitating insult irrespective of infarct timing. These findings demonstrate the changing vulnerability of the developing brain and show that hippocampal pathology is more closely related to the timing of an insult than seizure history or the occurrence of febrile convulsions. [source] Corpus callosum and posterior fossa development in monozygotic females: a morphometric MRI study of Turner syndromeDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2003Susannah L Fryer BA Previous neuroimaging research in Turner syndrome (TS) has indicated parietal lobe anomalies, while anomalies in other brain loci have been less well-substantiated. This study focused on potential cerebellar abnormalities and possible disruptions of interhemispheric (parietal) callosal connections in individuals with TS. Twenty-seven female children and adolescents with TS (mean age 13 years, SD 4 years 2 months) and 27 age-matched female control individuals (mean age 13 years 2 months, SD 4 years 1 month) underwent MRI. Age range of all participants was 7 to 20 years. Morphometric analyses of midline brain structures were conducted using standardized, reliable methods. When compared with control participants, females with TS showed reduced areas of the genu of the corpus callosum, the pons, and vermis lobules VI,VII, and an increased area of the fourth ventricle. No group difference in intracranial area measurements was observed. The reduced area of the genu in TS may reflect compromised connectivity between inferior parietal regions. Further, cerebellar vermis hypoplasia associated with TS agrees with literature that suggests the posterior fossa as a region prone to structural alterations in the face of early developmental insult. [source] The effect of prenatal hypoxia on brain development: short- and long-term consequences demonstrated in rodent modelsDEVELOPMENTAL SCIENCE, Issue 4 2006Hava Golan Hypoxia (H) and hypoxia-ischemia (HI) are major causes of foetal brain damage with long-lasting behavioral implications. The effect of hypoxia has been widely studied in human and a variety of animal models. In the present review, we summarize the latest studies testing the behavioral outcomes following prenatal hypoxia/hypoxia-ischemia in rodent models. Delayed development of sensory and motor reflexes during the first postnatal month of rodent life was observed by various groups. Impairment of motor function, learning and memory was evident in the adult animals. Activation of the signaling leading to cell death was detected as early as three hours following H/HI. An increase in the counts of apoptotic cells appeared approximately three days after the insult and peaked about seven days later. Around 14,20 days following the H/HI, the amount of cell death observed in the tissue returned to its basal levels and cell loss was apparent in the brain tissue. The study of the molecular mechanism leading to brain damage in animal models following prenatal hypoxia adds valuable insight to our knowledge of the central events that account for the morphological and functional outcomes. This understanding provides the starting point for the development and improvement of efficient treatment and intervention strategies. [source] Therapeutic approaches to epileptogenesis,Hope on the horizonEPILEPSIA, Issue 2010Asla Pitkänen Summary Prevention of epileptogenesis is an unmet need in medicine. During the last 3 years, however, several preclinical studies have demonstrated remarkable favorable effects of novel treatments on genetic and acquired epileptogenesis. These include the use of immunosuppressants and treatments that modify cellular adhesion, proliferation, and/or plasticity. In addition, the use of antiepileptic drugs in rats with genetic epilepsy or proconvulsants in acquired epilepsy models has provided somewhat unexpected favorable effects. This review summarizes these studies, and introduces some caveats when interpreting the data. In particular, the effect of genetic background, the severity of epileptogenic insult, the method and duration of seizure monitoring, and size of animal population are discussed. Furthermore, a novel scheme for defining epileptogenesis-related terms is presented. [source] Recommendation for a definition of acute symptomatic seizureEPILEPSIA, Issue 4 2010Ettore Beghi Summary Purpose:, To consider the definition of acute symptomatic seizures for epidemiological studies, and to refine the criteria used to distinguish these seizures from unprovoked seizures for specific etiologies. Methods:, Systematic review of the literature and of epidemiologic studies. Results:, An acute symptomatic seizure is defined as a clinical seizure occurring at the time of a systemic insult or in close temporal association with a documented brain insult. Suggestions are made to define acute symptomatic seizures as those events occurring within 1 week of stroke, traumatic brain injury, anoxic encephalopathy, or intracranial surgery; at first identification of subdural hematoma; at the presence of an active central nervous system (CNS) infection; or during an active phase of multiple sclerosis or other autoimmune diseases. In addition, a diagnosis of acute symptomatic seizure should be made in the presence of severe metabolic derangements (documented within 24 h by specific biochemical or hematologic abnormalities), drug or alcohol intoxication and withdrawal, or exposure to well-defined epileptogenic drugs. Discussion:, Acute symptomatic seizures must be distinguished from unprovoked seizures and separately categorized for epidemiologic purposes. These recommendations are based upon the best available data at the time of this report. Systematic studies should be undertaken to better define the associations in question, with special reference to metabolic and toxic insults, for which the time window for the occurrence of an acute symptomatic seizure and the absolute values for toxic and metabolic dysfunction still require a clear identification. [source] Facial Emotion Recognition after Curative Nondominant Temporal Lobectomy in Patients with Mesial Temporal SclerosisEPILEPSIA, Issue 8 2006Shearwood McClelland III Summary:,Purpose: The right (nondominant) amygdala is crucial for processing facial emotion recognition (FER). Patients with temporal lobe epilepsy (TLE) associated with mesial temporal sclerosis (MTS) often incur right amygdalar damage, resulting in impaired FER if TLE onset occurred before age 6 years. Consequently, early right mesiotemporal insult has been hypothesized to impair plasticity, resulting in FER deficits, whereas damage after age 5 years results in no deficit. The authors performed this study to test this hypothesis in a uniformly seizure-free postsurgical population. Methods: Controls (n = 10), early-onset patients (n = 7), and late-onset patients (n = 5) were recruited. All patients had nondominant anteromedial temporal lobectomy (AMTL), Wada-confirmed left-hemisphere language dominance and memory support, MTS on both preoperative MRI and biopsy, and were Engel class I 5 years postoperatively. By using a standardized (Ekman and Friesen) human face series, subjects were asked to match the affect of one of two faces to that of a simultaneously presented target face. Target faces expressed fear, anger, or happiness. Results: Statistical analysis revealed that the early-onset group had significantly impaired FER (measured by percentage of faces correct) for fear (p = 0.036), whereas the FER of the late-onset group for fear was comparable to that of controls. FER for anger and happiness was comparable across all three groups. Conclusions: Despite seizure control/freedom after AMTL, early TLE onset continues to impair FER for frightened expressions (but not for angry or happy expression), whereas late TLE onset does not impair FER, with no indication that AMTL resulted in FER impairment. These results indicate that proper development of the right amygdala is necessary for optimal fear recognition, with other neural processes unable to compensate for early amygdalar damage. [source] Cerebral Damage in Epilepsy: A Population-based Longitudinal Quantitative MRI StudyEPILEPSIA, Issue 9 2005Rebecca S. N. Liu Summary:,Purpose: Whether cerebral damage results from epileptic seizures remains a contentious issue. We report on the first longitudinal community-based quantitative magnetic resonance imaging (MRI) study to investigate the effect of seizures on the hippocampus, cerebellum, and neocortex. Methods: One hundred seventy-nine patients with epilepsy (66 temporal lobe epilepsy, 51 extratemporal partial epilepsy, and 62 generalized epilepsy) and 90 control subjects underwent two MRI brain scans 3.5 years apart. Automated and manual measurement techniques identified changes in global and regional brain volumes and hippocampal T2 relaxation times. Results: Baseline hippocampal volumes were significantly reduced in patients with temporal lobe epilepsy and could be attributed to an antecedent neurologic insult. Rates of hippocampal, cerebral, and cerebellar atrophy were not syndrome specific and were similar in control and patient groups. Global and regional brain atrophy was determined primarily by age. A prior neurologic insult was associated with reduced hippocampal and cerebellar volumes and an increased rate of cerebellar atrophy. Significant atrophy of the hippocampus, neocortex, or cerebellum occurred in 17% of patients compared with 6.7% of control subjects. Patients with and without significant volume reduction were comparable in terms of seizure frequency, antiepileptic drug (AED) use, and epilepsy duration, with no identifiable risk factors for the development of atrophy. Conclusions: Overt structural cerebral damage is not an inevitable consequence of epileptic seizures. In general, brain volume reduction in epilepsy is the cumulative effect of an initial precipitating injury and age-related cerebral atrophy. Significant atrophy developed in individual patients, particularly those with temporal lobe and generalized epilepsy. Longer periods of observation may detect more subtle effects of seizures. [source] Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxideEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2004W. B. Borke Abstract Background, Perinatal asphyxia is associated with cardiac dysfunction, and it is important to prevent further tissue injury during resuscitation. There is increasing evidence that myocardial matrix metalloproteinases (MMPs) are involved in myocardial hypoxaemia,reoxygenation injury. Objective, To assess MMPs and antioxidant capacity in newborn pigs after global ischaemia and subsequent resuscitation with ambient air or 100% O2 at different PaCO2 -levels. Methods, Newborn pigs (12,36 h of age) were resuscitated for 30 min by ventilation with 21% or 100% O2 at different PaCO2 levels after a hypoxic insult, and thereafter observed for 150 min. In myocardial tissue extracts, MMPs were analyzed by gelatin zymography and broad matrix-degrading capacity (total MMP). Total endogenous antioxidant capacity in myocardial tissue extracts was measured by the oxygen radical absorbance capacity (ORAC) assay. Results, Matrix metalloproteinase-2 more than doubled from baseline values (P < 0·001), and was higher in piglets resuscitated with 100% O2 than with ambient air (P = 0·012). The ORAC value was considerably decreased (P < 0·001). In piglets with elevated PaCO2, total MMP-activity in the right ventricle was more increased than in the left ventricle (P = 0·008). In the left ventricle, total MMPactivity was higher in the piglets with low PaCO2 than in the piglets with elevated PaCO2 (P = 0·013). Conclusion, In hypoxaemia-reoxygenation injury the MMP-2 level was highly increased and was most elevated in the piglets resuscitated with 100% O2. Antioxidant capacity was considerably decreased. Assessed by total MMP-activity, elevated PaCO2 during resuscitation might protect the left ventricle, and probably increase right ventricle injury of the myocardium. [source] Autoantibodies in alcoholic liver diseaseADDICTION BIOLOGY, Issue 2 2000Ian G. McFarlane Despite many decades of research, the reasons why only a relatively small proportion of individuals who consume excessive quantities of alcohol develop clinically significant liver disease remain unknown. The association with features of autoimmune diseases, including hypergammaglobulinaemia, circulating autoantibodies, inheritance of certain immunogenetic (HLA) markers and response to corticosteroid therapy in some patients has led to a persistent impression that altered immune regulation with a relative loss of self-tolerance underlies susceptibility to the development of the more severe forms of alcoholic liver disease (alcoholic hepatitis and/or cirrhosis). However, review of the data from the numerous studies that have been conducted over the past 30 years fails to reveal sufficiently convincing evidence that autoimmunity plays a primary role in alcohol-related liver damage. In particular, most of the wide range of circulating autoantibodies that have been reported in patients are found mainly at low titres, are not confined to those with severe liver injury, and are probably more likely to be a response to the hepatic insult than causally related to liver damage. Additionally, an association with various HLA phenotypes has not been confirmed by meta-analysis. Interpretation is complicated by evidence that alcohol may have direct effects on some components of the immune system but, if there is an immunogenetic basis for alcoholic liver disease, the present evidence suggests that this might be related more to cytokine gene polymorphisms than to a predisposition to autoimmunity per se. [source] Correlation of a high D-dimer level with poor outcome in traumatic intracranial hemorrhageEUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2007J.-R. Kuo The correlations between D-dimer and Glasgow Coma Scale (GCS), pupillary light reflex, distance of midline shift on brain computed tomography (CT), and Glasgow Outcome Score (GOS) in patients with trauma/non-trauma intracranial hemorrhage (ICH) are not consistent in studies. Ninety-eight traumatic and 59 non-traumatic ICH patients were studied. Pre-existing venous thrombosis, recent surgery, drug use (aspirin or coumadin), or malignancy, were excluded. D-dimer level was estimated within hours after acute insult, and statistical analyses were used for comparisons between groups. Traumatic ICH patients had higher D-dimer levels than controls (2984 vs. 256 ,g/l; P = 0.001). The GCS, midline shift on brain CT, pupillary reflex, and GOS at 3 months were significantly correlated with high D-dimer value in traumatic patients (individual P < 0.001), but not in the non-traumatic group. Using receiver-operating characteristic curve (ROC), the cutoff point was 1496 ,g/l, with sensitivity and specificity of 100% and 83%, respectively. D-dimer ,1496 ,g/l predicted a poor outcome [adjusted odds ratio (OR) 14.44, 95% CI 1.16,179.27; P = 0.038]. A high D-dimer level is associated with a poor outcome in patients with traumatic ICH. It can be used in addition to neurological assessment to predict the outcome. [source] Differential impact of brain damage on the access mode to memory representations: an information theoretic approachEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2007Rosapia Lauro-Grotto Abstract Different access modes to information stored in long-term memory can lead to different distributions of errors in classification tasks. We have designed a famous faces memory classification task that allows for the extraction of a measure of metric content, an index of the relevance of semantic cues for classification performance. High levels of metric content are indicative of a relatively preferred semantic access mode, while low levels, and similar correct performance, suggest a preferential episodic access mode. Compared with normal controls, the metric content index was increased in patients with Alzheimer's disease (AD), decreased in patients with herpes simplex encephalitis, and unvaried in patients with insult in the prefrontal cortex. Moreover, the metric content index was found to correlate with a measure of the severity of dementia in patients with AD, and to track the progression of the disease. These results underline the role of the medial-temporal lobes and of the temporal cortex, respectively, for the episodic and semantic routes to memory retrieval. Moreover, they confirm the reliability of information theoretic measures for characterizing the structure of the surviving memory representations in memory-impaired patient populations. [source] Minocycline attenuates hypoxia,ischemia-induced neurological dysfunction and brain injury in the juvenile ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006Lir-Wan Fan Abstract To investigate whether minocycline provides long-lasting protection against neonatal hypoxia,ischemia-induced brain injury and neurobehavioral deficits, minocycline was administered intraperitoneally in postnatal day 4 Sprague,Dawley rats subjected to bilateral carotid artery occlusion followed by exposure to hypoxia (8% oxygen for 15 min). Brain injury and myelination were examined on postnatal day 21 (P21) and tests for neurobehavioral toxicity were performed from P3 to P21. Hypoxic,ischemic insults resulted in severe white matter injury, enlarged ventricles, deficits in the hippocampus, reduction in numbers of mature oligodendrocytes and tyrosine hydroxylase-positive neurons, damage to axons and dendrites, and impaired myelination, as indicated by the decrease in myelin basic protein immunostaining in the P21 rat brain. Hypoxic,ischemic insult also significantly affected physical development (body weight gain and eye opening) and neurobehavioral performance, including sensorimotor and locomotor function, anxiety and cognitive ability in the P21 rat. Treatments with minocycline significantly attenuated the hypoxia,ischemia-induced brain injury and improved neurobehavioral performance. The protection of minocycline was associated with its ability to reduce microglial activation. The present results show that minocycline has long-lasting protective effects in the neonatal rat brain in terms of both hypoxia,ischemia-induced brain injury and the associated neurological dysfunction. [source] Dietary phytoestrogens improve stroke outcome after transient focal cerebral ischemia in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006María C. Burguete Abstract As phytoestrogens are postulated as being neuroprotectants, we assessed the hypothesis that dietary isoflavone-type phytoestrogens are neuroprotective against ischemic stroke. Transient focal cerebral ischemia (90 min) was induced by middle cerebral artery occlusion (MCAO) following the intraluminal thread technique, both in rats fed with soy-based diet and in rats fed with isoflavone-free diet. Cerebro-cortical laser-Doppler flow (cortical perfusion, CP), arterial blood pressure, core temperature, PaO2, PaCO2, pH and glycemia were measured before, during and after MCAO. Neurological examination and infarct volume measurements were carried out 3 days after the ischemic insult. Dietary isoflavones (both glycosides and aglycones) were measured by high-performance liquide chromatography. Neither pre-ischemic, intra-ischemic nor post-ischemic CP values were significantly different between the soy-based diet and the isoflavone-free diet groups. Animals fed with the soy-based diet showed an infarct volume of 122 ± 20.2 mm3 (19 ± 3.3% of the whole ipsilateral hemisphere volume). In animals fed with the isoflavone-free diet the mean infarct volume was significantly higher, 191 ± 26.7 mm3 (28 ± 4.1%, P < 0.05). Neurological examination revealed significantly higher impairment in the isoflavone-free diet group compared with the soy-based diet group (3.3 ± 0.5 vs. 1.9 ± 0.5, P < 0.05). These results demonstrate that dietary isoflavones improve stroke outcome after transient focal cerebral ischemia in such a way that a higher dietary isoflavone content results in a lower infarct volume and a better neurological status. [source] Role of gap junctional coupling in astrocytic networks in the determination of global ischaemia-induced oxidative stress and hippocampal damageEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2006Jose L. Perez Velazquez Abstract While there is evidence that gap junctions play important roles in the determination of cell injuries, there is not much known about mechanisms by which gap junctional communication may exert these functions. Using a global model of transient ischaemia in rats, we found that pretreatment with the gap junctional blockers carbenoxolone, 18,-glycyrrhetinic acid and endothelin, applied via cannulae implanted into the hippocampus in one hemisphere, resulted in decreased numbers of TUNEL-positive neurons, as compared with the contralateral hippocampus that received saline injection. Post-treatment with carbenoxolone for up to 30 min after the stroke injury still resulted in decreased cell death, but post-treatment at 90 min after the ischaemic insult did not result in differences in cell death. However, quinine, an inhibitor of Cx36-mediated gap junctional coupling, did not result in appreciable neuroprotection. Searching for a possible mechanism for the observed protective effects, possible actions of the gap junctional blockers in the electrical activity of the hippocampus during the ischaemic insult were assessed using intracerebral recordings, with no differences observed between the saline-injected and the contralateral drug-injected hippocampus. However, a significant reduction in lipid peroxides, a measure of free radical formation, in the hippocampus treated with carbenoxolone, revealed that the actions of gap junctional coupling during injuries may be causally related to oxidative stress. These observations suggest that coupling in glial networks may be functionally important in determining neuronal vulnerability to oxidative injuries. [source] Immune-related mechanisms participating in resistance and susceptibility to glutamate toxicityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002Hadas Schori Abstract Glutamate is an essential neurotransmitter in the CNS. However, at abnormally high concentrations it becomes cytotoxic. Recent studies in our laboratory showed that glutamate evokes T cell-mediated protective mechanisms. The aim of the present study was to examine the nature of the glutamate receptors and signalling pathways that participate in immune protection against glutamate toxicity. We show, using the mouse visual system, that glutamate-induced toxicity is strain dependent, not only with respect to the amount of neuronal loss it causes, but also in the pathways it activates. In strains that are genetically endowed with the ability to manifest a T cell-dependent neuroprotective response to glutamate insult, neuronal losses due to glutamate toxicity were relatively small, and treatment with NMDA-receptor antagonist worsened the outcome of exposure to glutamate. In contrast, in mice devoid of T cell-dependent endogenous protection, NMDA receptor antagonist reduced the glutamate-induced neuronal loss. In all strains, blockage of the AMPA/KA receptor was beneficial. Pharmacological (with ,2 -adrenoceptor agonist) or molecular intervention (using either mice overexpressing Bcl-2, or DAP-kinase knockout mice) protected retinal ganglion cells from glutamate toxicity but not from the toxicity of NMDA. The results suggest that glutamate-induced neuronal toxicity involves multiple glutamate receptors, the types and relative contributions of which, vary among strains. We suggest that a multifactorial protection, based on an immune mechanism independent of the specific pathway through which glutamate exerts its toxicity, is likely to be a safer, more comprehensive, and hence more effective strategy for neuroprotection. It might suggest that, because of individual differences, the pharmacological use of NMDA-antagonist for neuroprotective purposes might have an adverse effect, even if the affinity is low. [source] N -methyl- d -aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following strokeEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001Andreas Arvidsson Abstract Neurogenesis in the adult rat dentate gyrus was studied following focal ischemic insults produced by middle cerebral artery occlusion (MCAO). Animals were subjected to either 30 min of MCAO, which causes damage confined to the striatum, or 2 h of MCAO, which leads to both striatal and cortical infarction. When compared to sham-operated rats, MCAO-rats showed a marked increase of the number of cells double-labelled for 5-bromo-2,-deoxyuridine-5,-monophosphate (BrdU; injected during 4,6 days postischemia) and neuronal-specific antigen (NeuN; a marker of postmitotic neurons) in the ipsilateral dentate granule cell layer and subgranular zone at 5 weeks following the 2 h insult. Only a modest and variable increase of BrdU-labelled cells was found after 30 min of MCAO. The enhanced neurogenesis was not dependent on cell death in the hippocampus, and its magnitude was not correlated to the degree of cortical damage. Systemic administration of the N -methyl- d -aspartate (NMDA) receptor blocker dizocilpine maleate (MK-801) completely suppressed the elevated neurogenesis following 2 h of MCAO. Our findings indicate that stroke leads to increased neurogenesis in the adult rat dentate gyrus through glutamatergic mechanisms acting on NMDA receptors. This modulatory effect may be mediated through changes in the levels of several growth factors, which occur after stroke, and could influence various regulatory steps of neurogenesis. [source] Personality terms of abuse in three cultures: type nouns between description and insultEUROPEAN JOURNAL OF PERSONALITY, Issue 2 2005Boele De Raad In this study terms of abuse are investigated in three different cultures. Spontaneous verbal aggression is to a certain extent reminiscent of the values of a certain culture. One hundred and ninety-two male subjects from Spain, Germany and the Netherlands were asked to write down terms of abuse that they would use given a certain stimulus situation, and in addition to give their rating of the offensive character of those terms. A total set of 830 useful expressions was thus collected. The frequencies of the expressions were established, and the total list of expressions was categorized in terms of what they were about. In Spanish abusive language is typically about family and relations, in Germany it is typically about anal aspects, and in the Netherlands it is mainly about genitals. Explanations are provided in terms of dimensions on which the three cultures differ. Copyright © 2004 John Wiley & Sons, Ltd. [source] COSTS OF AN INDUCED IMMUNE RESPONSE ON SEXUAL DISPLAY AND LONGEVITY IN FIELD CRICKETSEVOLUTION, Issue 10 2004Alain Jacot Abstract Immune system activation may benefit hosts by generating resistance to parasites. However, natural resources are usually limited, causing a trade-off between the investment in immunity and that in other life-history or sexually selected traits. Despite its importance for the evolution of host defense, state-dependent fitness costs of immunity received little attention under natural conditions. In a field experiment we manipulated the nutritional condition of male field crickets Gryllus campestris and subsequently investigated the effect of an induced immune response through inoculation of bacterial lipopolysaccharides. Immune system activation caused a condition-dependent reduction in body condition, which was proportional to the condition-gain during the preceding food-supplementation period. Independent of nutritional condition, the immune insult induced an enduring reduction in daily calling rate, whereas control-injected males fully regained their baseline level of sexual signaling following a temporary decline. Since daily calling rate affects female mate choice under natural conditions, this suggests a decline in male mating success as a cost of induced immunity. Food supplementation enhanced male life span, whereas the immune insult reduced longevity, independent of nutritional status. Thus, immune system activation ultimately curtails male fitness due to a combined decline in sexual display and life span. Our field study thus indicates a key role for fitness costs of induced immunity in the evolution of host defense. In particular, costs expressed in sexually selected traits might warrant the honest advertisement of male health status, thus representing an important mechanism in parasite-mediated sexual selection. [source] | ||||||||||||||||||||||||||||||||||||||||||||||