Abstract
We performed in vivo PET imaging with 3-[18F]F-CP118,954 (1) for acetylcholinesterase (AChE) and [18F]fluoromethyl-PBR28-d2 (2) for translocator protein 18-kDa (TSPO) to investigate the inflammatory brain response after stroke. Imaging studies were performed in the middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model for a period of three weeks. The percentage injected dose per tissue weight (%ID/g) of striatum of 1, and cortex of 2 were obtained, respectively. To trace the sequential inflammatory responses, AChE imaging of 1 was done on post-MCAO day 2, after giving cold PK-11195 for 1 day, and TSPO imaging of 2 was carried out on post-MCAO day 11, after giving donepezil for 10 days. AChE activity in the MCAO-lesioned side were significantly higher than that of the contralateral side on day one, and TSPO activity was highest on day 11. TSPO inhibitor, PK-11195 did not affect AChE activity on day two, while AChE inhibitor, donepezil significantly lowered TSPO binding on day 12. Our study demonstrates that AChE level is elevated in the early course of brain ischemia as a trigger for the inflammatory response, and TSPO level is elevated persistently throughout the post-ischemic injury in the brain. Also, the AChE inhibitor may be able to inhibit or delay neurotoxic inflammatory responses and serve as a beneficial treatment option.
Highlights
Less than 10% of total ischemic stroke patients benefit from thrombolytic therapy, due to the narrow time window of disease progression [2]
Thrombolytic therapyrelated complications, such as intracranial hemorrhage occurs in about 6% [3]
Triphenyltetrazolium chloride (TTC) staining of rat brain was conducted to validate the middle cerebral artery occlusion (MCAO) surgery at day 11 and measured the infarct volume (Figure 3)
Summary
Ischemic stroke is a sudden neurologic deficit resulting in high mortality and morbidity. Numerous clinical trials are ongoing, in order to improve its outcomes, but still has limited results [1]. One reason for the high mortality is due to the limitation of effective treatment options, which are mainly focused on thrombolysis during the acute stage. Thrombolytic therapy is the most effective treatment in improving outcomes by providing reperfusion to the cerebral tissues before irreversible neuronal death. Less than 10% of total ischemic stroke patients benefit from thrombolytic therapy, due to the narrow time window of disease progression [2]. Thrombolytic therapyrelated complications, such as intracranial hemorrhage occurs in about 6% [3]. Thrombolytic therapy-related complications, such as intracranial hemorrhage occurs
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