Inflammatory processes are important mediators of 6-OHDA induced cell death. Under normal conditions, the SN contains a large number of Aliskiren Hemifumarate microglia as dopaminergic neurons are in a state of constant oxidative stress due to the production of ROS during DA metabolism. Indeed, we found Iba-1 immunoreactive microglia were present within the SN of sham animals. Although microglia are vital to the control of Sennoside-C immune and homeostatic functions within the brain, once activated they produce inflammatory cytokines such as IL-1, IL-6, and TNF-a, glutamate and quinolinic acid, superoxide radicals and NO. A major source of ROS is microglial NADPH oxidase. In PD, both NADPH oxidase and ROS production are upregulated due to increased microglial activation. ROS may cause apoptosis of neurons by inducing mitochondrial dysfunction and damaging lipids, proteins and DNA. Indeed, ROS are thought to be major contributors to 6-OHDA-mediated cell death. Notably, microglia express NK1 receptors and SP is considered to be a potent microglial activator. In the current study, an increase in Iba-1 positive microglia was observed prior to TH neuronal loss, confirming that the appearance of activated microglia may proceed neurodegeneration. Moreover, activation of microglia correlated with the degree of dopaminergic degeneration, as SP treated animals had both the greatest loss of DA neurons and the most nigral Iba-1 and ED-1 immunoreactive microglia. Conversely, animals treated with the NK1 antagonists had less Iba-1 immunoreactive microglia and a small reduction in the number of ED-1 positive microglia. Thus, inhibition of microglial activation using the SP, NK1 receptor antagonists may have contributed to the protection of dopaminergic neurons. Astrocytes also express the NK1 receptor, and once activated by SP, NF-kb translocates to the nucleus resulting in cytokine secretion. An increase in GFAP positive reactive astrocytes was observed in the SN of all 6-OHDA groups. Reactive astrocytes may be beneficial by metabolizing excess cytosolic DA and through secretion of glial- and brain-derived neurotrophic factors and antioxidant enzymes. Conversely, their secretion of pro-inflammatory cytokines may contribute to inflammatory processes and injury.