Time sequential monitoring of the translocator protein 18 kDa (TSPO) and acetylcholinesterase (AChE) expression in a middle cerebral artery occlusion (MCAO) rat model using PET radiotracers

Objectives Ischemia induced neuroinflammation in stroke is a critical process in the ischemia-reperfusion injury 1. The involvement of inflammatory mediators differs according to the time window after stroke. We used two different biomarkers for the post-stroke brain inflammatory response, TSPO, which is a membrane bound protein on the mitochondria, and a biomarker of reactive gliosis 2, and AChE which is one of the major components of the cholinergic anti-inflammatory pathway in the nervous system. Here, we evaluated the post-stroke inflammatory response according to the time course of post-ischemic injury using TSPO and AChE imaging radiotracers.

Methods We prepared two different targeted PET imaging radiotracers; [18F]fluoromethyl-PBR28 (1) for TSPO and 3-[18F]fluoro-CP-118,954 (2) for AChE. Serial neuroinflammation imaging of 1 and 2 was performed in MCAO Sprague Dawley rat models during 3 weeks. Specific binding ratios (SBRs) of the cortex were obtained, with the cerebellum as the reference region. Wilcoxon signed rank test was used to compare the SBRs of the MCAO lesion and the contralateral normal cortex.

Results MCAO lesional SBRs of TSPO image was highest on day 11, compared with the contralateral cortex (2.0 vs 0.0) and decreased gradually till day 21 (0.9 vs 0.0). In contrast, MCAO lesional SBRs of AChE image was highest on day 1, compared with the contralateral cortex (1.3 vs 0.8), and decreased gradually till day 15 (0.8 vs 0.8).

Conclusions Our results indicate that an AChE level elevate in the early course of disease and becomes normal, while TSPO expression elevates later, and is sustained throughout the post-ischemic injury. It is known that different inflammatory mechanisms are involved according to the time window after stroke 4. AChE was reported to be related with early apoptosis after stroke. TSPO related cytokines such as TNF-α and IL-6 increased later. Our study shows that the brain inflammatory process can be demonstrated and quantified with PET imaging. RESEARCH SUPPORT: .