Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Complement proteins and activation products have been found associated with neuropathology in Alzheimer's disease (AD). Recently, a C5a receptor antagonist was shown to suppress neuropathology in two murine models of AD, Tg2576 and 3xTg. Previously, a genetic deficiency of C1q in the Tg2576 mouse model showed an accumulation of fibrillar plaques similar to the complement sufficient Tg2576, but reactive glia were significantly decreased and neuronal integrity was improved suggesting detrimental consequences for complement activation in AD. The goal of this study was to define the role of the classical complement activation pathway in the progression of pathology in the 3xTg mouse that develops tangles in addition to fibrillar plaques (more closely reflecting human AD pathology) and to assess the influence of complement in a model of AD with a higher level of complement hemolytic activity.</p> <p>Methods</p> <p>3xTg mice deficient in C1q (3xTgQ-/-) were generated, and both 3xTg and 3xTgQ-/- were backcrossed to the BUB mouse strain which has higher in vitro hemolytic complement activity. Mice were aged and perfused, and brain sections stained for pathological markers or analyzed for proinflammatory marker expression.</p> <p>Results</p> <p>3xTgQ-/- mice showed similar amounts of fibrillar amyloid, reactive glia and hyperphosphorylated tau as the C1q-sufficient 3xTg at the ages analyzed. However, 3xTg and 3xTgQ-/- on the BUB background developed pathology earlier than on the original 3xTg background, although the presence of C1q had no effect on neuropathological and pro-inflammatory markers. In contrast to that seen in other transgenic models of AD, C1q, C4 and C3 immunoreactivity was undetectable on the plaques of 3xTg in any background, although C3 was associated with reactive astrocytes surrounding the plaques. Importantly, properdin a component of the alternative complement pathway was associated with plaques in all models.</p> <p>Conclusions</p> <p>In contrast to previously investigated transgenic models of AD, development of neuropathology in 3xTg mice, which progresses much slower than other murine models, may not be influenced by fibrillar amyloid mediated activation of the classical complement pathway, suggesting that the alternative complement pathway activation or a C3-independent cleavage of C5 could account for the detrimental effects in these mice that are prevented by the C5a receptor antagonist. Furthermore, the paucity of complement activation may be a factor in the slower kinetics of progression of pathology in the 3xTg model of this disease.</p

Laparoscopy for the hepatologist and general surgeon

Un équipement avec accessoires de petite taille pour 2e ponction est proposé en laparoscopie diagnostique. Le diamètre externe du trocart n'est que de 4 mm. Chez plusieurs centaines de patients à haut risque. divers accessoires - pinces à biopsies - canules de coagulation, d'aspiration - ont été utilisés sans complications sérieuses ni accident mortel. Les dimensions réduites facilitent et rendent plus sûres l'introduction du trocart et les manipulations. En raison de la réduction de l'espace entre viscères et péritoine pariétal, ces instruments résolvent les difficultés techniques. La préférence est donnée à des trocarts standards (6-7 mm) plutôt qu'aux larges trocarts (10-12 mm) utilisés en laparophotographie. Une tige de quartz, pré-stérilisée, reliée à un flash externe, est introduite par un 3" site de ponction, après utilisation du pneumopéritoine. La câble de fibres fournit l'éclairage séparé destiné à l'observation visuelle. Un système synchronisé permet l'adaptation du générateur flash à une caméra 35 mm. La transmission lumineuse est supérieure et sans distorsion chromatique au moyen des tiges de quartz et au départ des sources lumineuses actuellement disponibles. Une documentation précise peut être obtenue même à distance de la lésion