This likely contributed to suppressed DArgic neurodegeneration. The surviving neurons with elevated Bcl-xL expression then would affect the actions of glial cells within their vicinity. Neurons fated to die may activate microglial cells to accelerate neuronal degeneration, while surviving neurons may activate neuroprotective attributes of glial cells (Streit et al. 1999; Cullheim and Thams 2007). Regardless of the cause of brain injury, microglial cells respond to even minor pathologic events in the brain, evident by morphologic changes such as enlargement of their cell bodies and Inhibitors,research,lifescience,medical shortening

of their ramified processes (Kreutzberg 1996; Streit et al. 1999). 6-OHDA-treatment caused microglial activation with these types of morphologic changes. However, it is notable that the activated morphology was observed regardless

of the survival of DA neurons, with or without the cytokine mixture injection. Interestingly, Inhibitors,research,lifescience,medical many studies have described the harmful effects of activated microglia on neurons (Mosley et al. 2006; Long–Smith et al. 2009; Tansey and Goldberg 2010); however, our results suggest that this may not always be the case. There Inhibitors,research,lifescience,medical are some controversies regarding the activation of microglia (Liberatore et al. 1999; Henry et al. 2009; Marinova–Mutafchieva et al. 2009). Is their activation the cause or the result of DArgic neurodegeneration? Inhibitors,research,lifescience,medical Because DArgic neurodegeneration induced by selleck inhibitor 6-OHDA is a

rather chronic process (Henry et al. 2009; Marinova–Mutafchieva et al. 2009), it is conceivable that microglial activation may influence the fate of DArgic neurons even if the DArgic neurodegeneration precedes microglial activation. In fact, proinflammatory cytokines, such as IL-1β or TNFα, and reactive oxygen species, such as NO or superoxide, which are produced by microglia, have been implicated in the pathogenesis of PD (McGeer and McGeer 2008; Long–Smith Inhibitors,research,lifescience,medical et al. 2009; Yacoubian and Standaert 2009; Tansey and Goldberg 2010). The ameliorative effects of the cytokine mixture may be related to the functional changes of the activated microglia. The cytokine injection decreased the expression tuclazepam of IL-1β or TNFα in the SNpc of 6-OHDA-treated rats and it simultaneously increased expression of IGF-1 and HGF. IGF-1 (Guan et al. 2000; Ebert et al. 2008;) and HGF (Koike et al. 2006) have been shown for its ameliorative effects of 6-OHDA-induced rat Parkinsonism. Addition of GM-CSF and IL-3 to primary microglial cell cultures induced similar expression spectra of the proinflammatory cytokines and the neuroprotective factors. Thus, the action of the cytokine mixture to alter the microglial phenotype from a neurotoxic phenotype to a neuroprotective one, could at least partly explain the amelioration of 6-OHDA-induced Parkinsonism by the cytokine mixture.