2008). Nevertheless, it is important to bear in mind that minocycline has other pleiotropic actions, including matrix metalloproteinases-9 (MMP-9) inhibition, PARP or NFκB, scavenging of peroxynitrite, upregulation of bcl-2, and may affect cells other than microglia (Yong et al. 2004; Kim and Suh 2009). Other microglial inhibitors

render neuroprotection after stroke. PJ34, a potent poly(ADP-ribose) polymerase inhibitor, abolishes microglial activation and reduces hippocampal neuronal death by 84% if administered at 8 h after Inhibitors,research,lifescience,medical 10 min of global forebrain ischemia in rats (Hamby et al. 2007). Patients with acute stroke had a better neurological outcome with minocycline treatment (Lampl et al. 2007; Schabitz et al. 2008; Fagan et al. 2010). Recent in vitro and in vivo studies suggest that the neurotoxic actions of microglia during ischemia are mediated by microglial type II metabotropic receptors, TNF-α overproduction, NF-κB activation (Kaushal and Schlichter 2008), and Nox-1-dependent NADPH oxidase (Cheret

et Inhibitors,research,lifescience,medical al. 2008). In addition, it has been reported that caspase activation is an important mechanism underlying the deleterious functions of microglia (Burguillos et al. 2011). There are experimental evidences that microglial activation is detrimental for adult neurogenesis in different models of CNS injury Inhibitors,research,lifescience,medical (Ekdahl et al. 2003; Monje et al. 2003; Hoehn et al.

2005; Liu et al. 2007). Microglial activation selleck chemicals DAPT secretase impairs basal hippocampal adult neurogenesis induced by tissue damage associated with status epilepticus or lipopolysaccharide (LPS) infusion (Ekdahl et al. 2003). The impaired Inhibitors,research,lifescience,medical adult neuro-genesis is restored after microglial blockage using minocycline (Ekdahl et al. 2003). Minocycline or indomethacin treatment also enhances adult neurogenesis after MCAO in rodents (Hoehn et al. 2005; Liu et al. 2007). How to Explain the Dual Role of Microglia after Inhibitors,research,lifescience,medical CNS Diseases? We have seen that microglia have important physiological functions on the normal CNS and a dual role Cilengitide after neural disorders. How to explain this apparent paradox? In the following paragraphs, based on experimental evidences, including our own data, we propose a hypothesis to explain the dual role of microglia after CNS diseases. Microglia are fundamental components of brain innate immune system responsible for protecting neural tissue against infections (Olson and Miller 2004; Town et al. 2005; Lehnardt 2010). To perform such a role, microglia monitor the CNS environment using membrane molecules called “pattern recognition receptors” (PRRs) (Akira et al. 2006). These PRRs include toll-like sellekchem receptors (Olson and Miller 2004; Downes and Crack 2010), scavenger receptors (Husemann et al. 2002), and the complement receptor 3 Mac1 (Ross 2000).