@article{PonnuswamySchroettleOstermeieretal.2012,
  author    = {Ponnuswamy, Padmapriya and Schr{\"o}ttle, Angelika and Ostermeier, Eva and Gr{\"u}ner, Sabine and Huang, Paul L. and Ertl, Georg and Hoffmann, Ulrich and Nieswandt, Bernhard and Kuhlencordt, Peter J.},
  title     = {eNOS Protects from Atherosclerosis Despite Relevant Superoxide Production by the Enzyme in apoE\(^{-/-}\) Mice},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {1},
  doi       = {10.1371/journal.pone.0030193},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134866},
  pages     = {e30193},
  year      = {2012},
  abstract  = {Background: All three nitric oxide synthase (NOS) isoforms are expressed in atherosclerotic plaques. NOS enzymes in general catalyse NO production. However, under conditions of substrate and cofactor deficiency, the enzyme directly catalyse superoxide formation. Considering this alternative chemistry, the effects of NOS on key events in spontaneous hyperlipidemia driven atherosclerosis have not been investigated yet. Here, we evaluate how endothelial nitric oxide synthase (eNOS) modulates leukocyte/endothelial-(L/E) and platelet/endothelial-(P/E) interactions in atherosclerosis and the production of nitric oxide (NO) and superoxide by the enzyme. Principal Findings: Intravital microscopy (IVM) of carotid arteries revealed significantly increased L/E-interactions in apolipoproteinE/eNOS double knockout mice (apoE\(^{-/-}\)/eNOS\(^{-/-}\)), while P/E-interactions did not differ, compared to apoE\(^{-/-}\). eNOS deficiency increased macrophage infiltration in carotid arteries and vascular cell adhesion molecule-1 (VCAM-1) expression, both in endothelial and smooth muscle cells. Despite the expression of other NOS isoforms (inducible NOS, iNOS and neuronal NOS, nNOS) in plaques, Electron Spin Resonance (ESR) measurements of NO showed significant contribution of eNOS to total circulating and vascular wall NO production. Pharmacological inhibition and genetic deletion of eNOS reduced vascular superoxide production, indicating uncoupling of the enzyme in apoE\(^{-/-}\) vessels. Conclusion: Overt plaque formation, increased vascular inflammation and L/E-interactions are associated with significant reduction of superoxide production in apoE\(^{-/-}\)/eNOS\(^{-/-}\) vessels. Therefore, lack of eNOS does not cause an automatic increase in oxidative stress. Uncoupling of eNOS occurs in apoE\(^{-/-}\) atherosclerosis but does not negate the enzyme's strong protective effects.},
  language  = {en}
}
@article{PotreckMutkeWeylandetal.2021,
  author    = {Potreck, Arne and Mutke, Matthias A. and Weyland, Charlotte S. and Pfaff, Johannes A. R. and Ringleb, Peter A. and Mundiyanapurath, Sibu and M{\"o}hlenbruch, Markus A. and Heiland, Sabine and Pham, Mirko and Bendszus, Martin and Hoffmann, Angelika},
  title     = {Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy},
  series = {Translational Stroke Research},
  volume    = {12},
  journal   = {Translational Stroke Research},
  number    = {5},
  issn      = {1868-4483},
  doi       = {10.1007/s12975-020-00885-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308946},
  pages     = {799-807},
  year      = {2021},
  abstract  = {Despite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41-1.4) min-1 and was found in all 7 cases of hypoperfusion (100\%), in 10 of 16 cases of hyperperfusion (63\%), and in only three of 13 cases with unaffected perfusion (23\%). BBBD was significantly associated with hemorrhagic transformation (p < 0.001). While BBBD alone was not a predictor of clinical outcome at 3 months (positive predictive value (PPV) = 0.8 [0.56-0.94]), hypoperfusion occurred more often in patients with unfavorable clinical outcome (PPV = 0.43 [0.10-0.82]) compared to hyperperfusion (PPV = 0.93 [0.68-1.0]) or unaffected perfusion (PPV = 1.0 [0.75-1.0]). We show that combined perfusion and permeability imaging reveals distinct infarct signatures after recanalization, indicating the severity of prior ischemic damage. It assists in predicting clinical outcome and may identify patients at risk of stroke progression.},
  language  = {en}
}
@article{HoffmannPfeilAlfonsoetal.2016,
  author    = {Hoffmann, Angelika and Pfeil, Johannes and Alfonso, Julieta and Kurz, Felix T. and Sahm, Felix and Heiland, Sabine and Monyer, Hannah and Bendszus, Martin and Mueller, Ann-Kristin and Helluy, Xavier and Pham, Mirko},
  title     = {Experimental Cerebral Malaria Spreads along the Rostral Migratory Stream},
  series = {PLoS Pathogens},
  volume    = {12},
  journal   = {PLoS Pathogens},
  number    = {3},
  doi       = {10.1371/journal.ppat.1005470},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167434},
  pages     = {e1005470},
  year      = {2016},
  abstract  = {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.},
  language  = {en}
}