2007). In this study, Mac-2+ resident microglia release the proneurogenic molecule insulin-like growth factor (IGF-1), which

likely contribute to the microglia-induced neuroprotection (Lalancette-Hebert et al. 2007). Recent studies suggest that microglia may be beneficial by engulfing neutrophils (Neumann et al. 2008) and releasing TNF-α (Lambertsen Inhibitors,research,lifescience,medical et al. 2009) after ischemia. In addition, microglia may be beneficial through their phagocytic functions. Some studies suggest that phagocytosis of injured tissue is important for remodeling and may limit secondary damage following brain hemorrhage (Zhao et al. 2007). Recent studies suggest that microglia may shape hippocampal adult neurogenesis by clearing out apoptotic newborn cells, which illustrates the important phagocytic function of microglia (Sierra et al. 2010). Recently, we have shown that there is long-lasting microglial activation Inhibitors,research,lifescience,medical with a proneurogenic phenotype in SVZ after stroke (Thored et al. 2009). These glial cells release IGF-1 in late survival times after stroke, which has been confirmed by affymetrix analysis and quantitative polymerase chain reaction (PCR) (Thored et al. 2009). The results indicate Inhibitors,research,lifescience,medical that long-term activation of microglia in SVZ after stroke is important for regulating the previously described long-lasting neurogenesis in SVZ (Thored et al. 2006). Detrimental actions

of microglia after CNS diseases There is clear experimental evidence suggesting that overactivated microglia may be extremely detrimental following acute neural disorders, including SCI (Popovich et al. 1999, 2002; Gomes-Leal et al. 2005; Kigerl et al. 2009) and stroke (Yrjanheikki Inhibitors,research,lifescience,medical et al. 1999; Yong et al. 2004; Hewlett and Corbett 2006; Hayakawa et al. 2008; Schabitz et al. 2008; Wu et al. 2009; Fagan et al. 2010). Depletion of hematogenous macrophages with clodronate induces partial hindlimb recovery and neuroprotection after acute SCI (Popovich et al. 1999). Microglia/macrophage activation

seems to contribute to axonal damage following experimental injection of Inhibitors,research,lifescience,medical N-methyl-d-Aspartate (NMDA) (Gomes-Leal et al. 2005) and zymosan (Popovich et al. 2002) into the rat spinal cord. The semisynthetic tetra-cycline minocycline, an inhibitor of microglial found activation, reduces secondary oligodendrocyte and axonal degeneration as well as modulates apoptosis after SCI (Stirling et al. 2004) and cell cycle inhibition attenuates microglia-induced inflammatory response and decreases cell death after SCI (Tian et al. 2007). In addition, mild hypothermic treatment reduces spinal cord motor dysfunction by decreasing microglia activation (Morino et al. 2008). Blockage of microglial activation with minocycline induces conspicuous neuroprotection in both cortex and KPT-330 supplier striatum after experimental rat MCAO (Yrjanheikki et al. 1999).