Neuroinflammation contributes to neuronal degeneration in Parkinson's disease (PD). However, how brain inflammatory factors mediate the progression of neurodegeneration is still poorly understood. ...Experimental models of PD have shed light on the understanding of this phenomenon, but the exploration of inflammation-driven models is necessary to better characterize this aspect of the disorder. The use of lipopolysaccharide (LPS) to induce a neuroinflammation-mediated neuronal loss is useful to induce reliable elimination of dopaminergic neurons. Nevertheless, how this model parallels the PD-like neuroinflammation is uncertain. In the present work, we used the direct LPS injection as a model inductor to eliminate dopaminergic neurons of the substantia nigra pars compacta (SNpc) in rats and reevaluated the inflammatory reaction. High-resolution 3D histological examination revealed that, although LPS induced a reliable elimination of SNpc dopaminergic neurons, it also generated a massive inflammatory response. This inflammation-mediated injury was characterized by corralling, a damaged parenchyma occupied by a vast population of lesion-associated microglia and macrophages (LAMMs) undertaking wound compaction and scar formation, surrounded by highly reactive astrocytes. LAMMs tiled the entire lesion and engaged in long-standing phagocytic activity to resolve the injury. Additionally, modeling LPS inflammation in a cell culture system helped to understand the role of phagocytosis and cytotoxicity in the initial phases of dopaminergic degeneration and indicated that LAMM-mediated toxicity and phagocytosis coexist during LPS-mediated dopaminergic elimination. However, this type of severe inflammatory-mediated injury, and subsequent resolution appear to be different from the ageing-related PD scenario where the architectural structure of the parenchyma is mostly preserved. Thus, the necessity to explore new experimental models to properly mimic the inflammatory compound observed in PD degeneration.
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•LPS-induced mesencephalic injury causes corralling of microglia/macrophages•LPS-mediated lesion in SNpc triggers microglia/macrophages tiling and honeycomb structures•Microglia/macrophages tiling contributes to promote interactions with remnant dopaminergic neurons and debris•Corralled lesion shows high phagocytic capacity of dopaminergic remains
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
2.
Neuroinflammation in Movement Disorders Saavedra-López, E.; Casanova, P.V.; Cribaro, G.P. ...
Handbook of Basal Ganglia Structure and Function,
01/2016, Volume:
24
Book Chapter, Reference
Peer reviewed
Neuroinflammation is present in almost every injury of the central nervous system. This response is intended to resolve tissue damage and restore homeostasis. However, in pathological conditions, ...inflammation may cause direct damage and contribute to neuronal degeneration. Many, if not all, movement disorders show neuroinflammatory changes in the areas of tissue degeneration. Debate still persists on whether these inflammatory changes are a mere consequence or a cause of the local damage. Increasing data suggest the latter, since a broad range of pathological alterations, including genetic, are able to modify the inflammatory scenario and induce or at least contribute to the appearance of movement disorders. In the present chapter, we review inflammatory-mediated alterations in the most prevalent movement disorders, emphasizing the paradigm of Parkinson's disease, and suggest that anti-inflammatory drugs may be a positive therapeutic option for movement disorders.
