Effects of exercise training on intrauterine growth restriction in an animal model

Résumé Selon l'OMS, la retard de croissance intra-utérine (RCIU; 10% en dessous du poids normal pendant la grossesse) affecte 5-10% des grossesses et est une cause principale de la morbidité et de la mortalité périnatales. Dans notre étude précédente sur un modèle de souris transgénique de prééclampsie (R+A+), nous avons constaté que l’entraînement physique (ExT) avant et pendant la grossesse réduisait la pression artérielle maternelle et empêchait la RCIU en améliorant le développement placentaire. Dans le cadre de mon projet, nous avons confirmé les bénifices de l’ExT dans un modèle de RCIU (souris déficiente en p57Kip2 (p57-/+). Ainsi, nous avons observé la présence de RCIU, d’une masse placentaire réduite, d’une augmentation de la pathologie placentaire ainsi qu’une plus petite taille des portées chez les souris p57-/+ sédentaire. L’ExT prévient la RCIU ainsi que tous les paramètres mentionnés ci-haut. Nous avons observé que l'expression du facteur de croissance de l’endothélium vasculaire, un régulateur clé de l'angiogenèse lors de la croissance placentaire, était réduite dans le placenta des souris p57-/+ et normalisée par l’ExT. Nous avons également trouvé que l'expression en ARN dans le placenta de 2 facteurs inflammatoires (interleukine-1β et MCP-1) était augmenté chez les souris sédentaires p57-/+ alors que ceci n’était pas présent chez les souris entraînées, ce qui suggère que l'inflammation placentaire peut contribuer à la pathologie placentaire. Toutefois, contrairement aux souris R+A+, le système rénine-angiotensine placentaire chez les souris p57-/+ était normale et aucun effet de l’ExT a été observé. Ces résultats suggèrent que l’ExT prévient la RCIU en normalisant la pathologie placentaire, l’angiogenèse et l’inflammation placentaire.

Biocompatible properties of surgical mesh using an animal model

To study the biocompatibility of surgical meshes for use in pelvic reconstructive surgery using an animal model. Eight different types of mesh: Atrium, Dexon, Gynemesh, IVS tape, Prolene, SPARC tape, TVT tape and Vypro II, were implanted into the abdominal walls of rats for 3 months' duration. Explanted meshes were assessed, using light microscopy, for parameters of rejection and incorporation. Type 1 (Atrium, Gynemesh, Prolene, SPARC and TVT) and type 3 (Vypro II, Dexon and IVS) meshes demonstrated different biocompatible properties. Inflammatory cellular response and fibrosis at the interface of mesh and host tissue was most marked with Vypro II and IVS. All type 1 meshes displayed similar cellular responses despite markedly different mesh architecture. The inflammatory response and fibrous reaction in the non-absorbable type 3 meshes tested (IVS and Vypro II) was more marked than the type 1 meshes. The increased inflammatory and fibrotic response may be because of the multifilamentous polypropylene components of these meshes. Material and filament composition of mesh is the main factor in determining cellular response.

What does the animal model teach us about the effects of physical activity on growing bone?

Experiments to design physical activity programs that optimize their osteogenic potential are difficult to accomplish in humans. The aim of this article is to review the contributions that animal studies have made to knowledge of the loading conditions that are osteogenic to the skeleton during growth, as well as to consider to what extent animal studies fail to provide valid models of physical activity and skeletal maturation. Controlled loading studies demonstrate that static loads are ineffective, and that bone formation is threshold driven and dependent on strain rate, amplitude, and duration of loading. Only a few loading cycles per session are required, and distributed bouts are more osteogenic than sessions of long duration. Finally, animal models fail to inform us of the most appropriate ways to account for the variations in biological maturation that occur in our studies of children and adolescents, requiring the use of techniques for studying human growth and development.

Beta-amyloid deposition in the temporal lobe of patients with dementia with Lewy bodies:Comparison with non-demented cases and Alzheimer's disease

β-Amyloid (Aβ) deposition in regions of the temporal lobe in patients with dementia with Lewy bodies (DLB) was compared with elderly, non-demented (ND) cases and with Alzheimer's disease (AD). The distribution, density and clustering patterns of diffuse, primitive and classic Aβ deposits were similar in 'pure' DLB and ND cases. The distribution of Aβ deposits and the densities of the diffuse and primitive deposits were similar in 'mixed' DLB/AD cases compared with AD. However, the density of the classic deposits was significantly lower in DLB/AD compared with AD. In addition, the primitive Aβ deposits occurred more often in small, regularly spaced clusters in the tissue and less often in a single large cluster in DLB/AD compared with 'pure' AD. These results suggest that pure DLB and AD are distinct disorders which can coexist in some patients. However, the Aβ pathology of DLB/AD cases is not identical to that observed in patients with AD alone. (C) 2000 S. Karger AG, Basel.

Spatial patterns of the pathological changes in the temporal lobe of patients with neuronal intermediate filament inclusion disease

Neuronal intermediate filament inclusion disease (NIFID) is a new neurodegenerative disease characterized histologically by the presence of neuronal cytoplasmic inclusions (NI) immunopositive for intermediate filament proteins, neuronal loss, swollen achromatic neurons (SN), and gliosis. We studied the spatial patterns of these pathological changes parallel to the pia mater in gyri of the temporal lobe in four cases of NIFID. Both the NI and SN occurred in clusters that were regularly distributed parallel to the pia mater, the cluster sizes of the SN being significantly greater than those of the NI. In a significant proportion of areas studied, there was a spatial correlation between the clusters of NI and those of the SN and with the density of the surviving neurons. In addition, the clusters of surviving neurons were negatively correlated (out of phase) with the clusters of glial cell nuclei. The pattern of clustering of these histological features suggests that there is degeneration of the cortico-cortical projections in NIFID leading to the formation of NI and SN within the same vertical columns of cells. The glial cell reaction may be a response to the loss of neurons rather than to the appearance of the NI or SN.

Quantification of the pathological changes in the temporal lobe of patients with a novel neurofilamentopathy: neurofilament inclusion disease (NID)

Objective: To quantify the densities of neurofilament inclusions (NI), swollen achromatic neurons, surviving neurons and glial cells in a novel neurofilamentopathy neurofilament inclusion disease (NID). Material: Sectionsof temporal lobe from 4 cases of NID stained with an antibody raised to neurofilament proteins. Method: Densities of the pathological changes were estimated in the various gyri of the temporal lobe, hippocampus and dentate gyrus. Results: Densities of the NI and swollen achromatic neurons (SN) were greater in the cerebral cortical gyri than in the hippocampus and dentate gyrus. Lesion density was relatively constant between gyri and between the CA sectors of the hippocampus. In cortical gyri, the density of the NI, SN and glial cell nuclei was greater in laminae II/III than laminae V/VI. Densities of the NI were negatively correlated with the surviving neurons and positively correlated with the glial cell nuclei. The density of the SN was positively correlated with that of the surviving neurons. Conclusion: The pathology of NID morphologically resembles that of Pick's disease (PD) and corticobasal degeneration (CBD), but there are distinct differences between NID and these disorders supporting the hypothesis that NID is a novel and unique type of neurodegenerative disease.

Temporal lobe pathology of human patients with neurofilament inclusion disease

Neurofilament inclusion disease (NID) is a novel neurodegenerative disease characterized histologically by the presence of neurofilament positive neuronal inclusions (NI) and swollen achromatic neurons (SN). The density and distribution of NI and SN were studied in areas of the temporal lobe in four cases of NID. In NID, the density of the NI and SN was greater in areas of the cerebral cortex compared with the hippocampus and dentate gyrus. Lesion densities were similar in the different gyri of the temporal cortex and in the various cornu ammonis sectors of the hippocampus. In the cerebral cortex, the density of the NI and SN was greater in the lower compared with the upper cortical laminae. There was no significant correlation between the densities of the NI and SN. The distribution of the temporal lobe pathology of NID has several differences from that reported in Pick's disease and corticobasal degeneration supporting the hypothesis that NID is a novel and unique type of neurodegenerative disease. © 2003 Elsevier Ireland Ltd. All rights reserved.

Quantification of pathological lesions in the frontal and temporal lobe of ten patients diagnosed with Pick's disease

The densities of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) in the frontal and temporal lobe were determined in ten patients diagnosed with Pick's disease (PD). The density of PB was significantly higher in the dentate gyrus granule cells compared with the cortex and the CA sectors of the hippocampus. Within the hippocampus, the highest densities of PB were observed in sector CA1. PC were absent in the dentate gyrus and no significant differences in PC density were observed in the remaining brain regions. With the exception of two patients, the densities of SP and NFT were low with no significant differences in mean densities between cortical regions. In the hippocampus, the density of NFT was greatest in sector CA1. PB and PC densities were positively correlated in the frontal cortex but no correlations were observed between the PD and AD lesions. A principal components analysis (PCA) of the neuropathological variables suggested that variations in the densities of SP in the frontal cortex, temporal cortex and hippocampus were the most important sources of heterogeneity within the patient group. Variations in the densities of PB and NFT in the temporal cortex and hippocampus were of secondary importance. In addition, the PCA suggested that two of the ten patients were atypical. One patient had a higher than average density of SP and one familial patient had a higher density of NFT but few SP.

β-Amyloid (Aβ) deposition in the medial temporal lobe of patients with dementia with Lewy bodies

The distribution and density of diffuse, primitive and classic β-amyloid (Aβ) deposits in the medial temporal lobe (MTL) was studied in cases of dementia with Lewy bodies (DLB) with and without associated Alzheimer's disease (AD) and 15 cases of sporadic AD. In the 'pure' DLB cases, virtually no Aβ deposits were observed in the CA regions of the hippocampus or dentate gyrus whereas deposits were distributed throughout the MTL in DLB/AD and AD cases. Densities of diffuse and primitive Aβ deposits were similar in AD and DLB/AD cases but density was significantly reduced in the 'pure' DLB cases. The density of the classic deposits was significantly reduced in DLB cases with or without associated AD compared with AD cases. These results suggest that Aβ deposition in the MTL in 'pure' DLB cases is similar to that of elderly non-demented patients while, with the exception of the classic deposits, Aβ deposition in DLB/AD cases is similar to that in cases of AD alone.

A comparison of βamyloid (aβ deposition in the medial temporal lobe in late-onset sporadic Alzheimer's disease, and down's syndrome

The density of diffuse, primitive, classic and compact βamyloid (Aβ deposits was estimated in regions of the medial temporal lobe (MTL) in 15 cases of late-onset sporadic Alzheimer's disease (AD) and 12 cases of Down's syndrome (DS). A similar pattern of Aβ deposition was observed in the MTL in the AD and DS cases with a reduced density of deposits in the hippocampus compared with the adjacent cortical regions. Total Aβ deposit density was greater in DS than in AD in all brain regions examined. This could be attributable to overexpression of the amyloid precursor protein gene. The ratio of the primitive to the diffuse Aβ deposits was greater in DS than in AD which suggests that the formation of mature amyloid deposits is enhanced in DS. The diffuse deposits exhibited a parabolic and the primitive deposits an inverted parabolic response with age in the DS cases. This suggests either that the diffuse and primitive deposits are sequentially related or that there are alternate pathways of Aβ deposition. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Analysis of β-amyloid (Aβ) deposition in the temporal lobe in Alzheimer's disease using Fourier (spectral) analysis

To determine the spatial pattern of ß-amyloid (Aß) deposition throughout the temporal lobe in Alzheimer's disease (AD). Methods: Sections of the complete temporal lobe from six cases of sporadic AD were immunolabelled with antibody against Aß. Fourier (spectral) analysis was used to identify sinusoidal patterns in the fluctuation of Aß deposition in a direction parallel to the pia mater or alveus. Results: Significant sinusoidal fluctuations in density were evident in 81/99 (82%) analyses. In 64% of analyses, two frequency components were present with density peaks of Aß deposits repeating every 500–1000 µm and at distances greater than 1000 µm. In 25% of analyses, three or more frequency components were present. The estimated period or wavelength (number of sample units to complete one full cycle) of the first and second frequency components did not vary significantly between gyri of the temporal lobe, but there was evidence that the fluctuations of the classic deposits had longer periods than the diffuse and primitive deposits. Conclusions: (i) Aß deposits exhibit complex sinusoidal fluctuations in density in the temporal lobe in AD; (ii) fluctuations in Aß deposition may reflect the formation of Aß deposits in relation to the modular and vascular structure of the cortex; and (iii) Fourier analysis may be a useful statistical method for studying the patterns of Aß deposition both in AD and in transgenic models of disease.

A spatial pattern analysis of beta-amyloid (Abeta) deposition in the temporal lobe in Alzheimer's disease

To determine the factors influencing the distribution of -amyloid (Abeta) deposits in Alzheimer's disease (AD), the spatial patterns of the diffuse, primitive, and classic A deposits were studied from the superior temporal gyrus (STG) to sector CA4 of the hippocampus in six sporadic cases of the disease. In cortical gyri and in the CA sectors of the hippocampus, the Abeta deposits were distributed either in clusters 200-6400 microm in diameter that were regularly distributed parallel to the tissue boundary or in larger clusters greater than 6400 microm in diameter. In some regions, smaller clusters of Abeta deposits were aggregated into larger 'superclusters'. In many cortical gyri, the density of Abeta deposits was positively correlated with distance below the gyral crest. In the majority of regions, clusters of the diffuse, primitive, and classic deposits were not spatially correlated with each other. In two cases, double immunolabelled to reveal the Abeta deposits and blood vessels, the classic Abeta deposits were clustered around the larger diameter vessels. These results suggest a complex pattern of Abeta deposition in the temporal lobe in sporadic AD. A regular distribution of Abeta deposit clusters may reflect the degeneration of specific cortico-cortical and cortico-hippocampal pathways and the influence of the cerebral blood vessels. Large-scale clustering may reflect the aggregation of deposits in the depths of the sulci and the coalescence of smaller clusters.

An X-ray micro-fluorescence study to investigate the distribution of Al, Si, P and Ca ions in the surrounding soft tissue after implantation of a calcium phosphate-mullite ceramic composite in a rabbit animal model

Synthetic calcium phosphates, despite their bioactivity, are brittle. Calcium phosphate-mullite composites have been suggested as potential dental and bone replacement materials which exhibit increased toughness. Aluminium, present in mullite, has however been linked to bone demineralisation and neurotoxicity: it is therefore important to characterise the materials fully in order to understand their in vivo behaviour. The present work reports the compositional mapping of the interfacial region of a calcium phosphate-20 wt% mullite biocomposite/soft tissue interface, obtained from the samples implanted into the long bones of healthy rabbits according to standard protocols (ISO-10993) for up to 12 weeks. X-ray micro-fluorescence was used to map simultaneously the distribution of Al, P, Si and Ca across the ceramic-soft tissue interface. A well defined and sharp interface region was present between the ceramic and the surrounding soft tissue for each time period examined. The concentration of Al in the surrounding tissue was found to fall by two orders of magnitude, to the background level, within similar to 35 mu m of the implanted ceramic.

Temporal lobe pathology in neurodegenerative disease:a comparative study of eight disorders with special reference to the hippocampus

The temporal lobe is a major site of pathology in a number of neurodegenerative diseases. In this chapter, the densities of the characteristic pathological lesions in various regions of the temporal lobe were compared in eight neurodegenerative disorders, viz., Alzheimer’s disease (AD), Down’s syndrome (DS), dementia with Lewy bodies (DLB), Pick’s disease (PiD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), sporadic Creutzfeldt-Jakob disease (sCJD), and neuronal intermediate filament inclusion disease (NIFID). Temporal lobe pathology was observed in all of these disorders most notably in AD, DS, PiD, sCJD, and NIFID. The regions of the temporal lobe affected by the pathology, however, varied between disorders. In AD and DS, the greatest densities of ?-amyloid (A?) deposits were recorded in cortical regions adjacent to the hippocampus (HC), DS exhibiting greater densities of A? deposits than AD. Similarly, in sCJD, greatest densities of prion protein (PrPsc) deposits were recorded in cortical areas of the temporal lobe. In AD and PiD, significant densities of neurofibrillary tangles (NFT) and Pick bodies (PB) respectively were present in sector CA1 of the HC while in CBD, the greatest densities of tau-immunoreactive neuronal cytoplasmic inclusions (NCI) were present in the parahippocampal gyrus (PHG). Particularly high densities of PB were present in the DG in PiD, whereas NFT in AD and Lewy bodies (LB) in DLB were usually absent in this region. These data confirm that the temporal lobe is an important site of pathology in the disorders studied regardless of their molecular ‘signature’. However, disorders differ in the extent to which the pathology spreads to affect the HC which may account for some of the observed differences in clinical dementia.