Reducing Hypermuscularization of the Transitional Segment between Arterioles and Capillaries Protects Against Spontaneous Intracerebral Hemorrhage

International audienceBackground: Spontaneous deep intracerebral hemorrhage (ICH) is a devastating subtype of stroke without specific treatments. It has been thought that smooth muscle cell (SMC) degeneration at the site of arteriolar wall rupture may be sufficient to cause hemorrhage. However, deep ICHs are rare in some aggressive small vessel diseases that are characterized by significant arteriolar SMC degeneration. Here we hypothesized that a second cellular defect may be required for the occurrence of ICH. Methods: We studied a genetic model of spontaneous deep ICH using Col4a1+/G498V and Col4a1+/G1064D mouse lines that are mutated for the alpha1 chain of Collagen type IV. We analyzed cerebroretinal microvessels, performed genetic rescue experiments, vascular reactivity analysis and computational modeling. We examined post-mortem brain tissues from patients with sporadic deep ICH. Results: We identified in the normal cerebroretinal vasculature a novel segment between arterioles and capillaries, herein called the transitional segment (TS), that is covered by mural cells distinct from SMCs and pericytes. In Col4a1 mutant mice, this TS was hypermuscularized, with a hyperplasia of mural cells expressing more contractile proteins, whereas the upstream arteriole exhibited a loss of SMCs. Mechanistically, TS showed a transient increase in proliferation of mural cells during post-natal maturation. Mutant brain microvessels, unlike mutant arteries, displayed a significant upregulation of SM genes and Notch3 target genes, and genetic reduction of Notch3 in Col4a1+/G498V mice protected against ICH. Retina analysis showed that hypermuscularization of the TS was attenuated but arteriolar SMC loss unchanged in Col4a1+/G498V, Notch3+/- mice. Moreover, hypermuscularization of the retinal TS increased its contractility and tone and raised the intravascular pressure in the upstream feeding arteriole. We similarly found hypermuscularization of the TS and focal arteriolar SMC loss in brain tissues from patients with sporadic deep ICH. Conclusions: Our results suggest that hypermuscularization of the TS, via increased Notch3 activity, is involved in the occurrence of ICH in Col4a1 mutant mice, by raising the intravascular pressure in the upstream feeding arteriole and promoting its rupture at the site of SMC loss. Our human data indicate that these 2 mutually reinforcing vascular defects may represent a general mechanism of deep ICH

Caracterização física do resíduo de uma estação de tratamento de água para sua utilização em materiais de construção

Resumo A produção de água tratada, nas Estações de Tratamento de Água (ETAs) gera lodo, também chamado de resíduo de ETA (RETA). A maior parte das ETAs descarrega estes resíduos em meios hídricos, apesar da política nacional de resíduos sólidos salientar que é de responsabilidade da fonte geradora adotar destinação sustentável aos resíduos, visto que o seu lançamento in natura nos corpos hídricos é prejudicial, tornando esse meio de disposição um sério passivo ambiental das companhias de saneamento. O objetivo do presente trabalho foi realizar a caracterização física do resíduo gerado em uma ETA buscando obter parâmetros com bases normativas e considerar alternativas sustentáveis de reincorporação do lodo na cadeia produtiva para confecção de materiais de construção, de maneira a reduzir o impacto causado com o lançamento do RETA nos cursos de água. Para isso, foram realizados ensaios de índices de consistência do resíduo, granulometria, microscopia de varredura eletrônica e espectroscopia por dispersão de energia. Os resultados encontrados nas análises do resíduo demonstram a potencialidade de sua aplicação em substituição parcial do solo e/ou da areia, sendo suas propriedades similares a matéria-prima, na fabricação de materiais de construção