| OCR Text |
Show 63 in the peripheral circulation and by microglia and astrocytes in the brain (Gorina et al., 2011; van Noort and Bsibsi, 2009). Following bacterial invasion and LPS binding to immunologically active cells expressing TLR4, complex intracellular cascades are mobilized leading to alteration of cellular function for the purpose of clearing the invading pathogen (Medzhitov et al., 1997; Muzio et al., 2000). In contrast to humans, rodents respond to peripheral LPS-exposure in a complex multiphase fashion (Derijk et al., 1994; Rudaya et al., 2005). During the acute phase of LPS-induced (5 mg/kg i.p.) peripheral inflammation, C57Bl/6 mice become hypothermic. The acute phase is followed by complex patterns of thermoregulatory oscillations, which depend on the extent of LPS exposure (Morrow and Opp, 2005; Rudaya et al., 2005). In vivo administration of LPS (5 mg/kg i.p.) provokes a robust astrocytic response, as defined by increased GFAP expression, which subsides within 7 days (Kalmár et al., 2001; Zamanian et al., 2012). Astrocytes appear to respond to LPS and other immunologically active compounds, such as cytokines (Ronco et al., 2014), differently than in other pathological states such as stroke (Zamanian et al., 2012) or Aβ42-exposure (Ronco et al., 2014). This suggests that astrocytes may respond in a disease-specific fashion. Due to technological limitations for directly monitoring intracellular astrocytic dynamics, LPS-induced changes in astrocytic function are still not well-understood, especially in terminal fine processes where important astrocytic-neuronal interactions take place. Altered calcium dynamics have been previously described in LPS-exposed cultured astrocytes using synthetic calcium dyes, such as Fura-2 AM (Hamby et al., 2012; Ronco et al., 2014; Strokin et al., 2011). However, bulk-loaded synthetic dyes are not taken up by mature tissue and do not readily diffuse into distal fine processes. Thus, their use is limited to somatic and large proximal process activity in immature cells (Reeves et al., 2011). It |
