Characterization of arachnoid cysts using clinical chemistry, qualitative and quantitative proteomics

Abstract

Arachnoid cyst are benign intracranial lesions with a reported prevalence up to 1.1 % in the population. The origin of such cysts and the mechanisms of filling and sustaining are poorly understood. The aim of the thesis was to characterize the arachnoid cyst fluid and compare it with cerebrospinal fluid from the same individuals to evaluate the content of arachnoid cysts, as well as to gain further knowledge of the mechanisms of filling and sustaining of such cysts. Patients were recruited prior to elective surgery for fenestration of symptomatic arachnoid cysts in the temporal fossa and arachnoid cyst fluid and cerebrospinal fluid was collected with written informed consent from 19 patients. In Paper I the content of arachnoid cyst fluid and cerebrospinal fluid from the same patients were compared by clinical chemistry. The protein content of arachnoid cyst fluid is reduced relative to cerebrospinal fluid, while the concentration of phosphate is elevated. The results from this evaluation indicated that arachnoid cyst fluid is not identical to cerebrospinal fluid. In Paper II the protein content in arachnoid cyst fluid from 15 patients was evaluated by qualitative proteomics and the findings were compared with published databases of plasma and cerebrospinal fluid. These comparisons indicated that the arachnoid cyst fluid proteome was similar to cerebrospinal fluid, but dissimilar to plasma. In Paper III we performed a quantitative comparison of the proteomes of arachnoid cyst fluid and cerebrospinal fluid for five patients. 348 proteins were quantified in individual patients, and 1425 proteins in a pool of the same patients using an iTRAQ-strategy combined with extensive fractionation. We identify differences between the fluids, but currently we are not able to elute the biological significance. Searched against DNA and mRNA-data, we find some differences, but not in patterns of biological significance. This is the first quantitative proteomics comparison of AC fluid and CSF. In conclusion, the work presented in this thesis indicates that AC fluid is similar, but not identical, to CSF. Results do not support oncotic filling or valves as mechanisms for filling and sustaining of arachnoid cysts but rather an active or selective mechanism for filling.