Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects

Background: Retinitis pigmentosa is a heterogeneous group of inherited neurodegenerative retinal disorders characterized by a progressive peripheral vision loss and night vision difficulties, subsequently leading to central vision impairment. Chronic microglia activation is associated with various neurodegenerative diseases including retinitis pigmentosa. The objective of this study was to quantify microglia activation in the retina of P23H rats, an animal model of retinitis pigmentosa, and to evaluate the therapeutic effects of TUDCA (tauroursodeoxycholic acid), which has been described as a neuroprotective compound. Methods: For this study, homozygous P23H line 3 and Sprague-Dawley (SD) rats were injected weekly with TUDCA (500 mg/kg, ip) or vehicle (saline) from 20 days to 4 months old. Vertical retinal sections and whole-mount retinas were immunostained for specific markers of microglial cells (anti-CD11b, anti-Iba1 and anti-MHC-II). Microglial cell morphology was analyzed and the number of retinal microglial was quantified. Results: Microglial cells in the SD rat retinas were arranged in regular mosaics homogenously distributed within the plexiform and ganglion cell layers. In the P23H rat retina, microglial cells increased in number in all layers compared with control SD rat retinas, preserving the regular mosaic distribution. In addition, a large number of amoeboid CD11b-positive cells were observed in the P23H rat retina, even in the subretinal space. Retinas of TUDCA-treated P23H animals exhibited lower microglial cell number in all layers and absence of microglial cells in the subretinal space. Conclusions: These results report novel TUDCA anti-inflammatory actions, with potential therapeutic implications for neurodegenerative diseases, including retinitis pigmentosa.This research was supported by grants from the Spanish Ministry of Economy and Competitiveness-FEDER (BFU2012-36845), Instituto de Salud Carlos III (RETICS RD12/0034/0010), Organización Nacional de Ciegos Españoles (ONCE), FUNDALUCE, Asociación Retina Asturias and Fundación Jesús de Gangoiti

Motion of the dipolarization front during a flow burst event observed by Cluster

In this paper we study a flow burst event which took place during enhanced geomagnetic activity on July 22, 2001, when Cluster was located in the postmidnight magnetotail. The flow burst was associated with a clear dipolarization ahead of the high-speed part of the predominantly Earthward directed flow. Based on the analysis of the four spacecraft data, we found that a similar to2000 km thick dipolarization front moves Earthward and dawnward with a speed of similar to77 km/s. The plasma before this front is deflected, consistent with the plasma ahead of a localized plasma bubble centered at midnight side being pushed aside by the moving obstacle. The main body of the high-speed flow is directed mainly parallel to the dipolarization front. These observations indicate that the evolution of the dipolarization front across the tail is directly coupled with the fast flow