A B S T R A C T This study was designed to investigate the mechanisms involved in fibromusculoelastic lesion formation produced by selective de-endothelialization by the intra-arterial balloon catheter technique in thrombocytopenic rabbits. Thrombocytopenia was induced and maintained for up to 31 days by daily injections of highly specific sheep anti-rabbit platelet sera (APS). Evidence for re-endothelialization was obtained by i.v. Evans blue dye 30 min before sacrifice. Rabbits received daily injections of APS, which reduced the mean platelet count to 5,600/cm3; control animals received identically treated normal sheep sera on the same schedule, and had mean daily platelet counts of 363,000/cm3. Evaluation of intimal thickness was assessed by counting cell layers in semithin sections. Intimal thickening in aortae from rabbits treated with APS was strikingly suppressed, in contrast to those from normal sheep sera-treated animals which showed a mean intimal thickness of 18 cell layers within 28 days often after de-endothelialization. Re-endothelialization was not affected by APS treatment. These results indicate that the proliferation of smooth muscle cells which is characteristic ofarteriosclerotic lesions is dramatically inhibited by reduction of platelets.
SUMMARY The formation of arteriosclerotic fibromusculoelastic intimal thickening following arterial de-endothelialization is well documented. Recent findings, both in vitro and in vivo, suggest that platelets are a major participant in the pathogenesis of this lesion by releasing a mitogen to medial smooth muscle cells (SMC). This mitogen results in SMC migration to and proliferation within the intima. A similar mitogen has been described as originating in brain and pituitary tissue. We now report that, in hypophysectomized rats with normal platelet counts, intimal hyperplasia is markedly delayed; pair-fed intact controls normally develop lesions. It therefore appears that the pituitary gland plays a significant role in the experimental arteriosclerotic response.ARTERIOSCLEROTIC plaque formation proceeds by the intimal accumulation of cells and extracellular connective tissue that progressively narrows the vessel lumen. Vascular smooth muscle cells (SMC) appear to play the major role in this proliferative process; they migrate lumenally from the vessel media, through the internal elastic lamina following endothelial cell injury, 1 ' 2 proliferate, 3 and have demonstrated the in vitro ability to synthesize many extracellular connective tissue proteins found within the matrix of the arteriosclerotic plaque.4 ' 5 Therefore, influencing SMC migration and proliferation following endothelial cell injury should significantly affect development of the arteriosclerotic lesion. Recent evidence indicates that platelets promote the proliferation of cultured SMCs, 6 ' 7 as well as migration and proliferation of SMCs after vascular intimal injury in vivo.8 ' 9 This effect appears to be mediated via a mitogen carried by platelets and released with platelet adhesion. In addition, a mitogenic factor isolated from bovine brain and pituitary gland has been described, which promotes proliferation of fibroblasts in culture and which has biological properties similar to those of the platelet mitogenic factor. 10' " This similarity between mitogens led us to explore the in vivo role of the pituitary gland during the proliferative arterial response that follows endothelial cell removal. MethodsExperimental animals were male Sprague-Dawley rats, weighing 250-300 g, half of which were hypophysectomized. They were purchased from a commercial breeder (Charles River Laboratories) and were allowed to acclimate for 2 weeks after arrival before further surgical procedures were performed. During this period, each rat received 6% glucose in its drinking water for the first 7 days, followed thereafter by tap water, ad libitum. The control (nonhypophysectomized) rats were pair-fed, and all rats were housed at 37°C throughout the entire experiment. Confirmation of HypophysectomyUnder ether anesthesia, the rats were first bled from their tails into heparinized vacutainer tubes (no. 3204KA; Becton-Dickenson) for plasma corticosterone levels, which served as an initial index of pituitary function. Each of the hypophysectomized rats had a plasma cortic...
SUMMARY Histological and biochemical studies were made of the brains of 13 hydrocephalic adult cats and 7 control animals in order to establish whether there is any significant variation in the size or number of brain cells as a result of hydrocephalus and whether such variation could be a factor limiting repair of cerebral damage. The results suggest that cerebral white matter is primarily affected by hydrocephalus, and that the ventricles can expand without significant cellular loss. It is concluded that the disruption of myelin may be a factor which limits repair but that loss of cells is not a significant factor. RÉSUMÉ Effet des hydrocéphalies sévères sur la taille et le nombre de cellules cérébrales Des études histologiques et biochemiques ont été effectuées à partir de cerveaux de 13 chats hydrocéphales et de 7 animaux témoins dans le but d'établir s'il apparait une variation significative dans la taille ou le nombre des cellules cérébrales du fait de l'hydrocéphalie et si de telles variations pourraient être un facteur limitant la récupération d'un trouble cérébral. Les résultats suggèrent que l'hydrocéphalie altère principalement la substance blanche cérébrale et qu'on peut noter one augmentation de la taille des ventricules cérébraux sans perte cellulaire significative. Il en est déduit que l'altération de la myéline peut être un facteur limitant définitivement la réparation mais qu'une perte de cellules n'est pas un facteur significatif à craindre. ZUSAMMENFASSUNG Der Einfluβ eines schweren Hydrocephalus auf die Gröβe und Anzahl des Hirnzellen An Gehirnen von 13 hydrocephalen ausgewachsenen Katzen und 7 Kontrolltieren wurden histologische und biochemische Untersuchungen durchgeführt, um festzustellen, ob es signifikante Unterschiede in Größe und Anzahl der Hirnzellen gibt, die bedingt sind durch einen Hydrocephalus, und ob ein solcher Unterschied als limitierender Faktor für die Besserung eines Hirnschadens in Frage käme. Die Ergebnisse zeigen, daß vorwiegend die weiße Hirnsubstanz durch den Hydrocephalus geschädigt wird und daβ sich die Hirnventrikel ohne nennenswerten Zellverlust ausdehnen können. Man schließt daraus, daß durch den Myelinzerfall der Hirnschaden irreparabel sein könnte, daß jedoch der Zellzerfall nicht als signifikanter Faktor dafür in Frage kommt. RESUMEN Efecto de la hidrocefalia grave sobre el tamaño y número de células cerebrales Se realizaron estudios histológicos y bioquímicos en los cerebros de 13 gatos adultos hidrocefalicos y 7 animales de control con el objeto de establecer si existe una variación significativa en el tamaño o numero de las células cerebrales como resultado de una hidrocefalia y si esta variación podría constituir un factor limitante de la reparación del daño cerebral. Los resultados sugieren que la substancia blanca cerebral es lo que se afecta primariamente en la hidrocefalia, y que los ventrículos cerebrales pueden expanderse sin pérdida celular significativa. Se concluye que la disrupción de la mielina puede ser un facto que limite la reparación, pero la ...
SUMMARY The purpose of this study was to ascertain the sequence of events and the cellular constituents involved in reconstituting the cortical mantle after ventricular shunting. The subjects were severely hydrocephalic adult cats. After insertion of a shunt, the ventricular system rapidly returned to normal size and there was gross reconstitution of the cortical mantle. However, there still remained in the cortical mantle many of the histological changes seen before insertion of the shunt. The effect of hydrocephalus is mainly upon axons in the periventricular white matter. The axons become stretched and finally disrupted, resulting in disintegration of the surrounding myelin. In the absence of axons, remyelination cannot take place. It would seem, therefore, that prompt reversal of hydrocephalus is necessary in order to preserve the anatomical and functional integrity of the brain. RÉSUMÉ Reconstitution du manteau cortical dans l'hydrocéphalic corrigée par shunt Le but de cette étude était de préciser la suite des évènements et les caractéristiques cellulaires impliquées dans la reconstitution du manteau cortical après shunt ventriculaire. L'étude porte sur des chats adultes avec hydrocéphalic grave. Après insertion d'un shunt, le système ventriculaire est retourné rapidement à une taille normale et il y a eu une reconstitution grossière du manteau cortical. Cependant, beaucoup des modifications histologiques observées avant l'insertion du shunt demeurent dans le manteau cortical. Les effets de l'hydrocéphalie portent principalement sur les axones de la substance blanche périventriculaire. Lex axones sont étirés et finalement rompus avec désintégration de la gaine de myeline. En l'absence d'axones, la remyélinisation ne peut s'établir. Il semblerait done qu'une correction rapide de l'hydrocéphalie est nécessaire pour préserver l'intégrité anatomique et fonctionnelle du cerveau. ZUSAMMENFASSUNG Regeneration des Hirnmantels bei Hydrocephalus mil Ventil Es ist der Sinn dieser Arbeit Näheres über die Reihenfolge der Vorgänge und über die beteiligten zellulären Bestandteile zur Wiederherstellung des Hirnmantels nach einer Ventiloperation festzustellen. Das Untersuchungsmaterial bestand aus hochgradig hydrocephalen erwachsenen Katzen. Nach Implantation eines Ventils normalisierte sich die Größe des Ventrikelsystems sehr rasch und es fand sich eine deutliche Regeneration des Hirnmantels. Viele histologische Veränderungen, die vor der Ventilimplantation festgestellt wurden, blieben jedoch im Hirnmantel noch erhalten. Der Einfluß des Hydrocephalus macht sich hauptsächlich bei den Axonen in der periventrikulären weißen Substanz bemerkbar. Die Axone wurden gedehnt und sehließlich zerrissen. was zum Zerfall des benachbarten Myelins führte. Ohne Axone kann keine Remyelinisation erfolgen. Daher scheint eine möglichst schnelle Rückbildung des Hydrocephalus notwendig, urn die anatomische und funktionelle Integrität des Gehirns zu erhalten. RESUMEN Reconstitución del mando cortical en hidrocefalias corregidas con derivación El ...
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