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Figure 9 | Journal of Neuroinflammation

Figure 9

From: Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell death in the mouse MPTP model of Parkinson's disease

Figure 9

Schematic flow chart depicting the role of the vicious circle in dopaminergic neurotoxicity. For this study, the initial insult MPP+ exerts direct dopaminergic neurodegeneration (~30% of the original numbers). Neuronal damage initiates the vicious circle with COX-2 and microglia as the key components feeding oxidative and inflammatory damage to the neurons, which in turn progresses to the secondary damage/death which is coupled to the release of factors that initiate another cycle of oxidative and inflammatory insults. The positive feed back loop may continue until the additional neuronal death (~50% of the remaining of the initial death) combined with the initial loss exceed the amount needed for normal motor control (~80% total loss); thus the PD symptoms, such as postural instability or hypokinesia, occurs. This vicious circle helps explain the chronic and prolong nature of PD progression. It is hypothesized that the blockade of COX-2 activity by selective COX-2 inhibitors or deficiency of COX-2 would attenuate the vicious circle and alleviate dopaminergic neurotoxicity by directly reducing COX-2 free radical production as well as by indirectly decreasing microglial activation and subsequent microglia-mediated damage.

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