Detection of secondary neurodegeneration after subarachnoid hemorrhage in the rat using the PET tracer cis-4-[18F]fluoro-D-proline and functional MRI, and investigation of the neuroprotective effect of argon

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The patients’ impairments after a subarachnoid hemorrhage (SAH) cannot always be associated with focal structural brain lesions that could be detected by computer tomography (CT) or conventional magnetic resonance imaging (MRI). Furthermore, focal brain lesions are not always linked to neuropsychological deficits. The detection of neurodegenerative changes at an early stage after SAH is not possible at the moment.Positron emission tomography (PET) and autoradiography with the 18F-labeled amino acid cis-4-[18F]fluoro-D-proline (cisF18DPro) have proven to be very sensitive methods for the detection of secondary degenerative processes in caudate nucleus, thalamus and hippocampus in rat models of cortical infarction and brain tumor. Moreover, advanced MRI-methods like sodium imaging, water mapping and diffusion-weighted MRI offer new opportunities to detect subtle pathologic events in brain diseases that are not visible in conventional MRI at an early stage of disease.Furthermore, the biologically active noble gas argon has recently come into scientific focus. Its neuroprotective effects have been shown in different experimental models; moreover, unlike xenon, it lacks sedative side effects under normobaric conditions and has low acquisition costs.The aim of the present study is to investigate whether secondary neurodegeneration after SAH can be detected by cisF18DPro-PET or autoradiography and advanced MRI methods in an early stage of the disease. The trauma will be analyzed after different time points (3, 6, 9 days) using MRI, PET and autoradiography. By comparing the results with the uptake of a reference tracer (3H-deoxyglucose) and immunofluorescence, we intend to determine the value of the above mentioned imaging methods with regard to the detection of secondary neurodegenerative injuries. Moreover, we want to explore whether a treatment with argon at an early stage of SAH has beneficial effects on secondary damages and whether they can be detected and followed by the imaging methods mentioned above.The study aims at establishing novel PET and functional MRI methods as diagnostic tools for the early and non-invasive detection of secondary neuronal damage in patients with SAH and to investigate the neuroprotective effect of argon with the aim of optimizing the therapy and diagnosis, and to improve the prognosis in patients with SAH.