TY - JOUR A1 - Hoffmann, Angelika A1 - Pfeil, Johannes A1 - Alfonso, Julieta A1 - Kurz, Felix T. A1 - Sahm, Felix A1 - Heiland, Sabine A1 - Monyer, Hannah A1 - Bendszus, Martin A1 - Mueller, Ann-Kristin A1 - Helluy, Xavier A1 - Pham, Mirko T1 - Experimental Cerebral Malaria Spreads along the Rostral Migratory Stream JF - PLoS Pathogens N2 - It is poorly understood how progressive brain swelling in experimental cerebral malaria (ECM) evolves in space and over time, and whether mechanisms of inflammation or microvascular sequestration/obstruction dominate the underlying pathophysiology. We therefore monitored in the Plasmodium berghei ANKA-C57BL/6 murine ECM model, disease manifestation and progression clinically, assessed by the Rapid-Murine-Coma-and-Behavioral-Scale (RMCBS), and by high-resolution in vivo MRI, including sensitive assessment of early blood-brain-barrier-disruption (BBBD), brain edema and microvascular pathology. For histological correlation HE and immunohistochemical staining for microglia and neuroblasts were obtained. Our results demonstrate that BBBD and edema initiated in the olfactory bulb (OB) and spread along the rostral-migratory-stream (RMS) to the subventricular zone of the lateral ventricles, the dorsal-migratory-stream (DMS), and finally to the external capsule (EC) and brainstem (BS). Before clinical symptoms (mean RMCBS = 18.5±1) became evident, a slight, non-significant increase of quantitative T2 and ADC values was observed in OB+RMS. With clinical manifestation (mean RMCBS = 14.2±0.4), T2 and ADC values significantly increased along the OB+RMS (p = 0.049/p = 0.01). Severe ECM (mean RMCBS = 5±2.9) was defined by further spread into more posterior and deeper brain structures until reaching the BS (significant T2 elevation in DMS+EC+BS (p = 0.034)). Quantitative automated histological analyses confirmed microglial activation in areas of BBBD and edema. Activated microglia were closely associated with the RMS and neuroblasts within the RMS were severely misaligned with respect to their physiological linear migration pattern. Microvascular pathology and ischemic brain injury occurred only secondarily, after vasogenic edema formation and were both associated less with clinical severity and the temporal course of ECM. Altogether, we identified a distinct spatiotemporal pattern of microglial activation in ECM involving primarily the OB+RMS axis, a distinct pathway utilized by neuroblasts and immune cells. Our data suggest significant crosstalk between these two cell populations to be operative in deeper brain infiltration and further imply that the manifestation and progression of cerebral malaria may depend on brain areas otherwise serving neurogenesis. KW - experimental cerebral malaria KW - rostral-migratory-stream KW - brain swelling Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167434 VL - 12 IS - 3 ER - TY - JOUR A1 - Kurz, Felix T. A1 - Kampf, Thomas A1 - Buschle, Lukas R. A1 - Schlemmer, Heinz-Peter A1 - Bendszus, Martin A1 - Heiland, Sabine A1 - Ziener, Christian H. T1 - Generalized moment analysis of magnetic field correlations for accumulations of spherical and cylindrical magnetic perturbers JF - Frontiers in Physics N2 - In biological tissue, an accumulation of similarly shaped objects with a susceptibility difference to the surrounding tissue generates a local distortion of the external magnetic field in magnetic resonance imaging. It induces stochastic field fluctuations that characteristically influence proton spin dephasing in the vicinity of these magnetic perturbers. The magnetic field correlation that is associated with such local magnetic field inhomogeneities can be expressed in the form of a dynamic frequency autocorrelation function that is related to the time evolution of the measured magnetization. Here, an eigenfunction expansion for two simple magnetic perturber shapes, that of spheres and cylinders, is considered for restricted spin diffusion in a simple model geometry. Then, the concept of generalized moment analysis, an approximation technique that is applied in the study of (non-)reactive processes that involve Brownian motion, allows deriving analytical expressions of the correlation function for different exponential decay forms. Results for the biexponential decay for both spherical and cylindrical magnetized objects are derived and compared with the frequently used (less accurate) monoexponential decay forms. They are in asymptotic agreement with the numerically exact value of the correlation function for long and short times. KW - magnetized sphere/cylinder KW - magnetic susceptibility KW - correlation function KW - diffusion KW - magnetic resonance imaging Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190604 SN - 2296-424X VL - 4 ER -