Differential Imaging Findings in Parkinsonian Syndromes
Differential Imaging Findings in Dementias
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Microglia constitute 10-20% of the glial cells in the brain, and they form its natural defense mechanism. They are normally in a resting state, but local injury causes them to activate and swell, leading to the expression of human leukocyte antigens on the cell surface, and to release cytokines such as tumor necrosis factor and interleukins. The mitochondria of activated (but not resting) microglia express peripheral-type benzodiazepine binding sites, which might have a role, via membrane stabilization, in the prevention of cell apoptosis. The isoquinoline 11CPK 11195 binds selectively to peripheral-type benzodiazepine sites and, therefore, potentially provides an in vivo PET marker of microglial activa tion (Figure 3). This marker suffers, however, from having high nonspecific background and vascular signals, which complicates its kinetic modeling and lowers its sensitivity in practice.
The loss of substantia nigra neurons in PD has been shown to be associated with microglial activa tion, and histochemical studies have shown that, in PD, microglial activation can also be seen in other basal ganglia, along with the cingulate, hippocampus and cortical areas.[55] One series reported increased midbrain 11CPK 11195 PET signal in patients with PD, which correlated inversely with the levels of DAT binding in the posterior putamen, as measured by 11C2β-carbomethoxy-3β-(4-fluorophenyl)tropane (11C-β-CFT) PET.[56] In patients with advanced PD, Gerhard and co-workers reported additional microglial activation in the brainstem, striatum, pallidum and frontal cortex,[57] which is consistent with the distribution of Lewy body pathology that was reported by Braak and colleagues.[58] Interestingly, Gerhard et al. found little change in the extent of microglial activation over a 2-year follow-up period, although all the patients deteriorated clinically. This finding could imply that microglial activation is merely an epi phenomenon in PD. Postmortem studies have shown, however, that the microglia continue to express cytokine messenger RNA, which suggests that they could be driving disease progression.