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Title: In vivo imaging of post-ischaemic cellular changes : a longitudinal microPET study
Author: Hughes, J. L.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2006
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The ability to visualize the development of stroke-related brain damage in each individual is essential to gain a more complete understanding of the underlying mechanisms, which contribute to dysfunction, and potentially to aid clinical diagnosis. Previous positron emission tomography (PET) studies suggest the radioligands 11C-Flumazenil and 11C-PK11195 may be useful for in vivo investigation of selective neuronal loss and microglia activation. However, histological validation is lacking, while the time-course and inter-relationship between 11C-Flumazenil and 11C-PK11195 imaging are not fully understood. The ability to dynamically image stroke-related brain damage in vivo using these radioligands cannot be fully exploited in man. Consequently, this thesis describes the sequential use of both 11C-Flumazenil and 11C-PK11195, in combination with histopathological assessment, in a rodent temporary middle cerebral artery occlusion (tMCAo) model. Each subject was imaged at three time-points (1 hour, 48 hours and 14 days) after tMCAo. The model selected was characterised further and generated extensive cortical selective neuronal loss and microglial activation with very limited pan-necrosis. This is the first study to utilize a longitudinal MicroPET protocol to investigate ischaemia-induced cellular changes in a rodent model of stroke. The results indicate biphasic changes in 11C-Flumazenil binding in the occluded cortex following tMCAo, which challenge the current understanding of 11C-Flumazenil binding following ischaemia. Relationships with selective neuronal loss and pan-necrosis were complex, suggesting additional factors such as receptor plasticity may be contributing to the observed changes in 11C-Flumazenil binding; representing several temporally evolving pathosphysiological mechanisms in the ischaemic penumbra. The results presented also validate 11C-PK11195 as an in vivo marker of microglial activation in the reperfused penumbra, corroborating its usefulness to image inflammation after stroke in vivo.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available