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1.
A study was performed to determine the effect of zinc deficiency on the zinc concentration of the retina, lens, and the retinal pigment epithelium and choroid. Weanling, male Sprague-Dawley rats were fed ad libitum modified AIN-93 diets containing 3 mg zinc/kg diet (−Zn; n=10) for 6 wk. Control animals were pair-fed (+ZnPF; n=10) or fed ad libitum (+ZnAL; n=10) diets containing 100 mg zinc/kg diet. At 6 wk, plasma and tibia zinc were measured by flame atomic absorption spectrophotometry to confirm zinc deficiency. The zinc concentration of ocular tissues was measured by inductively coupled plasma-mass spectrometry. Mean (±SEM) lens zinc concentration was significantly depressed in the zinc-deficient group as compared to that of pair-fed or ad libitum-fed controls, suggesting that the role of zinc in cataract formation should be investigated. The zinc concentration of total neural retina was preserved in zinc deficiency. Previously reported deterioration of retinal function in zinc deficiency may be the result of a decline in the zinc concentration of a specific cell layer of the retina that cannot be detected on gross analysis of the entire retina. This work was presented in part at Experimental Biology 98, April 1998, San Francisco, CA [P. G. Paterson, B. H. Grahn, and J. S. Fabe, Retinal and lens zinc concentration in the zinc-deficient rat. FASEB J. 12, A521 (1998)].  相似文献   

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Gas bubble trauma (GBT) caused by gas supersaturation of river water continues to be a problem in the Columbia River Basin. A common indicator of GBT is the percent of the lateral line occluded with gas bubbles; however, this effect has never been examined in relation to lateral line morphology. The effects of 115, 125 and 130% total dissolved gas levels were evaluated on five fish species common to the upper Columbia River. Trunk lateral line pore diameters differed significantly (P<0.0001) among species (longnose sucker>largescale sucker>northern pikeminnow>/=chinook salmon>/=redside shiner). At all supersaturation levels evaluated, percent of lateral line occlusion exhibited an inverse correlation to pore size but was not generally related to total dissolved gas level or time of exposure. This study suggests that the differences in lateral line pore diameters between species should be considered when using lateral line occlusion as an indicator of gas bubble trauma.  相似文献   

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Concussion has been linked to the presence of injurious strains in the brain tissues. Research investigating severe brain injury has reported that strains in the brain may be affected by two parameters: magnitude of the acceleration, and duration of that acceleration. However, little is known how this relationship changes in terms of creating risk for brain injury for magnitudes and durations of acceleration common in sporting environments. This has particular implications for the understanding and prevention of concussive risk of injury in sporting environments. The purpose of this research was to examine the interaction between linear and rotational acceleration and duration on maximum principal strain in the brain tissues for loading conditions incurred in sporting environments. Linear and rotational acceleration loading curves of magnitudes and durations similar to those from impact in sport were used as input to the University College Brain Trauma Model and maximum principal strain (MPS) was measured for the different curves. The results demonstrated that magnitude and duration do have an effect on the strain incurred by the brain tissue. As the duration of the acceleration increases, the magnitude required to achieve strains reflecting a high risk of concussion decreases, with rotational acceleration becoming the dominant contributor. The magnitude required to attain a magnitude of MPS representing risk of brain injury was found to be as low as 2500 rad/s2 for impacts of 10–15 ms; indicating that interventions to reduce the risk of concussion in sport must consider the duration of the event while reducing the magnitude of acceleration the head incurs.  相似文献   

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The possible homology between anomalies of the corpus callosum in mice and in humans remains questionable. The small number of existing behavioural studies in mice have not shown effects, at the behavioural level, of the absence or reduction in size of the corpus callosum. We therefore examined the development, during the first 3 weeks of postnatal life, of a number of simple reflex and integrative responses in the members of a sample of 101 BALB/cCF mice; at autopsy carried out at 50 days of age, 29 mice showed anomalies of the corpus callosum (total absence or an area less than 0.75 mm2). Asymmetry of the development of these responses was measured either as the proportion of animals showing asymmetrical appearance of responses on the left and right sides, and as the delay between appearances on the left and right sides in "asymmetrical" mice. Both measures decreased over the first 15 postnatal days, at the same rate in normal and abnormal mice; in each case the decrease is better described by a second-order, quadratic, function than by a simple linear function. We therefore conclude that the integrity of the corpus callosum is not necessary for the normal maturation of sensorimotor behaviour in mice, and suggest that this conclusion may possibly be explained by the relatively recent appearance of mice in the mammalian radiation.  相似文献   

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Andermann syndrome is characterized by agenesis of corpus callosum, anterior horn cell disease, a mixed sensory and motor neuropathy, and facial dysmorphism, and is inherited as an autosomal recessive trait. A 7-month-old boy was admitted with developmental retardation. Head control was not gained and he could not sit. He had high arched palate, elongated facies and large angle of the mandible, which were compatible with the Andermann syndrome. Moderate hypotonicity and absent tendon reflexes were also noted. Serum creatine kinase level was normal. Magnetic resonance imaging of the brain showed agenesis of the corpus callosum. Electromyographic examination revealed the presence of both sensory and motor neuropathy. The patient was diagnosed as having the Andermann syndrome according to the clinical and laboratory findings and he is reported due to rare presentation.  相似文献   

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The corpus callosum is hypothesized to play a fundamental role in integrating information and mediating complex behaviors. Here, we demonstrate that lack of normal callosal development can lead to deficits in functional connectivity that are related to impairments in specific cognitive domains. We examined resting-state functional connectivity in individuals with agenesis of the corpus callosum (AgCC) and matched controls using magnetoencephalographic imaging (MEG-I) of coherence in the alpha (8-12 Hz), beta (12-30 Hz) and gamma (30-55 Hz) bands. Global connectivity (GC) was defined as synchronization between a region and the rest of the brain. In AgCC individuals, alpha band GC was significantly reduced in the dorsolateral pre-frontal (DLPFC), posterior parietal (PPC) and parieto-occipital cortices (PO). No significant differences in GC were seen in either the beta or gamma bands. We also explored the hypothesis that, in AgCC, this regional reduction in functional connectivity is explained primarily by a specific reduction in interhemispheric connectivity. However, our data suggest that reduced connectivity in these regions is driven by faulty coupling in both inter- and intrahemispheric connectivity. We also assessed whether the degree of connectivity correlated with behavioral performance, focusing on cognitive measures known to be impaired in AgCC individuals. Neuropsychological measures of verbal processing speed were significantly correlated with resting-state functional connectivity of the left medial and superior temporal lobe in AgCC participants. Connectivity of DLPFC correlated strongly with performance on the Tower of London in the AgCC cohort. These findings indicate that the abnormal callosal development produces salient but selective (alpha band only) resting-state functional connectivity disruptions that correlate with cognitive impairment. Understanding the relationship between impoverished functional connectivity and cognition is a key step in identifying the neural mechanisms of language and executive dysfunction in common neurodevelopmental and psychiatric disorders where disruptions of callosal development are consistently identified.  相似文献   

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It is known that four common inbred mouse strains show defects of the forebrain commissures. The BALB/cJ strain has a low frequency of abnormally small corpus callosum, whereas the 129 strains have many animals with deficient corpus callosum. The I/LnJ and BTBR T+ tf/J strains never have a corpus callosum, whereas half of I/LnJ and almost all BTBR show severely reduced size of the hippocampal commissure. Certain F1 hybrid crosses among these strains are known to be less severely abnormal than the inbred parents, suggesting that the parent strains have different genetic causes of commissure defects. In this study, all hybrid crosses among the four strains were investigated. The BTBR × I/Ln hybrid expressed almost no defects of the hippocampal commissure, unlike its inbred parent strains. Numerous three‐way crosses among the four strains yielded many mice with no corpus callosum and severely reduced hippocampal commissure, which shows that the phenotypic defect can result from several different combinations of genetic alleles. The F2 and F3 hybrid crosses of BTBR and I/LnJ had almost 100% absence of the corpus callosum but about 50% frequency of deficient hippocampal commissure. The four‐way hybrid cross among all four abnormal strains involved highly fertile parents and yielded a very wide phenotypic range of defects from almost no hippocampal commissure to totally normal forebrain commissures. The F2 and F3 crosses as well as the four‐way cross provide excellent material for studies of genetic linkage and behavioral consequences of commissure defects.  相似文献   

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BACKGROUND: Pai syndrome (PS) is a rare regional developmental defect of the face, mainly characterized by the variable association of midline cleft of the upper lip (MCL), duplicated maxillary median frenulum, and midline facial cutaneous and midanterior alveolar process polyps. Its entire clinical spectrum is still poorly delineated and the etiology remains unknown. CASE: We describe a 1-month-old boy presenting with MCL, left nostril hamartomatous mass, midline pedunculated polyp originating from the columella base, midline alveolar cleft, duplication of the upper median frenulum, unilateral persistent papillary membrane, lipoma of the corpus callosum, and additional minor facial dysmorphism. This patient also presents with agenesis of the corpus callosum, which has never been reported in PS. Literature review was carried out comparing clinical data of the 20 previously published patients with those observed in the present case. CONCLUSIONS: The minimum diagnostic criteria for PS has been fixed in one or more hamartomatous nasal polyps plus MCL (with or without cleft alveolus) and/or midanterior alveolar process congenital polyp. Additional common ancillary findings include duplicated median maxillary frenulum, hypertelorism, nasal cleft, midfrontal skin tags, and ocular and CNS structural abnormalities. However, mental retardation is only an occasional feature and seems to be related to coexisting conditions (such as chromosome imbalance). Literature review shows that PS is etiologically heterogeneous, as it may result from chromosome abnormalities and environmental/stochastic events, as well as de novo mutations.  相似文献   

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The corpus callosum (CC) is the major commissure connecting the cerebral hemispheres and there is evidence of its continuing development into young adulthood [Ann. Neurol. 34 (1993) 71]. Yet, little is known about changes in the size and tissue characteristics of its sub-regions. The sub-regions of the CC (genu, body, isthmus and splenium) are topographically organized to carry interhemispheric fibres representing heteromodal and unimodal cortical brain regions. Studies of the development of each of these sub-regions can therefore provide insights into the time course of brain development. We assessed age-related changes in the size and the signal intensities (SI) of the subregions of the corpus callosum in the Magnetic Resonance Imaging (MRI) scans of a cross-sectional sample of 109 healthy young individuals aged 7-32 years. Age was significantly positively correlated with the size of the callosal sub-regions (with the exception of the isthmus). On the other hand, there was an age-related decrease in SI across all the CC sub-regions. The rates of CC regional size increases appeared to be most pronounced in childhood. By contrast, SI decreases occurred during childhood and adolescence but reached an asymptote during young adulthood. Finally, the observed size and SI changes were similar across CC sub-regions. The observed increases in CC size in conjunction with the decreases in signal intensity reflect continued maturation of the structure from childhood through young adulthood. An increase in axonal size may underlie growth in the size of the CC during childhood. The continued decrease in the CC signal intensity during adolescence may in addition be related to ongoing maturation of the axonal cytoskeleton. CC maturational changes appeared synchronous across sub-regions suggesting parallel maturation of diverse brain regions during childhood and adolescence.  相似文献   

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BACKGROUND: Although experienced clinicians have been diagnosing fetal alcohol syndrome (FAS) for nearly 30 years, the rest of the spectrum of fetal alcohol damage is not being classified effectively. This article describes a quantification of neuroanatomical structure that may supply a useful discriminator of prenatal brain damage from alcohol. It is demonstrated in a data set of adults of both sexes. METHODS: Ninety adults (45 males) were examined by magnetic resonance imaging (MRI). These subjects were group-matched for age and ethnicity across three diagnoses: FAS, fetal alcohol effects (FAE), and normals. All FAS and FAE were heavily alcohol-exposed in utero; normals were not. From T(1)-weighted MR brain images, we extracted 3D morphometric representations of shape for 33-landmark point configurations and 40-point outlines of the corpus callosum along its midline (a slightly nonplanar structure). RESULTS: There are striking differences between exposed and unexposed in the statistical distributions of these two shapes. The differences are better characterized by excess variance in the exposed group than by any change in average landmark or outline shape. For each sex, combining the callosal outline data with the landmark data leads to a powerful quadratic discriminator of exposed from unexposed. The discriminating features include the relationship of brain stem to diencephalon, and localized variabilities of callosal outline shape, but not diagnosis (FAS vs. FAE). CONCLUSIONS: Statistical analysis of brain shape is a powerful new source of information relevant to fetal alcohol spectrum nosology and etiology. Patients with FAS and FAE do not differ in these brain shape features, but both differ from the unexposed. The aspects of brain shape that are especially variable may be entailed in the underlying neuroteratogenetic mechanisms.  相似文献   

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A Chinese hamster (male, 1-month-old) was found to have a large nodular mass at the left mandible. The tumor appeared to replace the entire left mandible, extending from the third molar to the incisor. The tumor mass occupied most of the oral cavity to compress the tongue ventrally. Histologically, the neoplasm was composed of islands of chondrocytes with bizarre and enlarged nuclei which were surrounded by poorly differentiated mesenchymal cells. The tumor involved the falx cerebri to compress the frontal crest of the cerebrum. On the basis of histological features, this tumor was diagnosed as chondrosarcoma.  相似文献   

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The role of the corpus callosum (CC) in the interhemispheric interaction of prosodic and syntactic information during speech comprehension was investigated in patients with lesions in the CC, and in healthy controls. The event-related brain potential experiment examined the effect of prosodic phrase structure on the processing of a verb whose argument structure matched or did not match the prior prosody-induced syntactic structure. While controls showed an N400-like effect for prosodically mismatching verb argument structures, thus indicating a stable interplay between prosody and syntax, patients with lesions in the posterior third of the CC did not show this effect. Because these patients displayed a prosody-independent semantic N400 effect, the present data indicate that the posterior third of the CC is the crucial neuroanatomical structure for the interhemispheric interplay of suprasegmental prosodic information and syntactic information.  相似文献   

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Increased blood concentrations of phenylalanine in patients with trauma and sepsis are common but unexplained. We examined the potential relationship between serum concentrations of phenylalanine and the immune activation marker neopterin in 84 specimens of 18 patients (14 males and 4 females) post-trauma during 12-14 days of follow up. Compared to healthy controls, average phenylalanine and neopterin concentrations were elevated in patients, and there existed a positive correlation between concentrations of the two analytes (r (s) = 0.375, p < 0.001). No such association existed between neopterin and tyrosine concentrations (r (s) = -0.018), but neopterin concentrations correlated to the phenylalanine to tyrosine ratio (r (s) = 0.328, p = 0.001). Increased phenylalanine implies insufficient conversion by phenylalanine (4)-hydroxylase (PAH). Oxidative stress due to immune activation and inflammation may destroy cofactor 5,6,7,8-tetrahydrobiopterin and impair PAH activity. This assumption is further supported by the correlation found between higher neopterin concentrations and higher phenylalanine to tyrosine ratio, which estimates efficacy of PAH.  相似文献   

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Repeated stressful events are known to be associated with onset of depression. Further, stress activates the hypothalamic-pituitary-adrenocortical (HPA) system by elevating plasma cortisol levels. However, little is known about the related downstream molecular pathway. In this study, by using repeated water-immersion and restraint stress (WIRS) as a stressor for mice, we attempted to elucidate the molecular pathway induced by elevated plasma corticosterone levels. We observed the following effects both, in vivo and in vitro: (1) repeated exposure to WIRS activates the 3-phosphoinositide-dependent protein kinase (PDK1)-serum glucocorticoid regulated kinase (SGK1)-N-myc downstream-regulated gene 1 (NDRG1)-adhesion molecule (i.e., N-cadherin, α-catenin, and β-catenin) stabilization pathway via an increase in plasma corticosterone levels; (2) the activation of this signaling pathway induces morphological changes in oligodendrocytes; and (3) after recovery from chronic stress, the abnormal arborization of oligodendrocytes and depression-like symptoms return to the control levels. Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms.  相似文献   

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It has been shown in vivo that Wnt5a gradients surround the corpus callosum and guide callosal axons after the midline (postcrossing) by Wnt5a-induced repulsion via Ryk receptors. In dissociated cortical cultures we showed that Wnt5a simultaneously promotes axon outgrowth and repulsion by calcium signaling. Here to test the role of Wnt5a/calcium signaling in a complex in vivo environment we used sensorimotor cortical slices containing the developing corpus callosum. Plasmids encoding the cytoplasmic marker DsRed and the genetically encoded calcium indicator GCaMP2 were electroporated into one cortical hemisphere. Postcrossing callosal axons grew 50% faster than pre-crossing axons and higher frequencies of calcium transients in axons and growth cones correlated well with outgrowth. Application of pharmacological inhibitors to the slices showed that signaling pathways involving calcium release through IP3 receptors and calcium entry through TRP channels regulate post-crossing axon outgrowth and guidance. Co-electroporation of Ryk siRNA and DsRed revealed that knock down of the Ryk receptor reduced outgrowth rates of postcrossing but not precrossing axons by 50% and caused axon misrouting. Guidance errors in axons with Ryk knockdown resulted from reduced calcium activity. In the corpus callosum CaMKII inhibition reduced the outgrowth rate of postcrossing (but not precrossing) axons and caused severe guidance errors which resulted from reduced CaMKII-dependent repulsion downstream of Wnt/calcium. We show for the first time that Wnt/Ryk calcium signaling mechanisms regulating axon outgrowth and repulsion in cortical cultures are also essential for the proper growth and guidance of postcrossing callosal axons which involve axon repulsion through CaMKII.  相似文献   

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