4 results on '"Hahn, Max"'
Search Results
2. An MR-based brain template and atlas for optical projection tomography and light sheet fluorescence microscopy in neuroscience
- Author
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Willekens, Stefanie M. A., Morini, Federico, Mediavilla, Tomás, Nilsson, Emma, Orädd, Greger, Hahn, Max, Chotiwan, Nunya, Visa, Montse, Berggren, Per-Olof, Ilegems, Erwin, Överby, Anna K., Ahlgren, Ulf, Marcellino, Daniel, Willekens, Stefanie M. A., Morini, Federico, Mediavilla, Tomás, Nilsson, Emma, Orädd, Greger, Hahn, Max, Chotiwan, Nunya, Visa, Montse, Berggren, Per-Olof, Ilegems, Erwin, Överby, Anna K., Ahlgren, Ulf, and Marcellino, Daniel
- Abstract
Introduction: Optical Projection Tomography (OPT) and light sheet fluorescence microscopy (LSFM) are high resolution optical imaging techniques, ideally suited for ex vivo 3D whole mouse brain imaging. Although they exhibit high specificity for their targets, the anatomical detail provided by tissue autofluorescence remains limited. Methods: T1-weighted images were acquired from 19 BABB or DBE cleared brains to create an MR template using serial longitudinal registration. Afterwards, fluorescent OPT and LSFM images were coregistered/normalized to the MR template to create fusion images. Results: Volumetric calculations revealed a significant difference between BABB and DBE cleared brains, leading to develop two optimized templates, with associated tissue priors and brain atlas, for BABB (OCUM) and DBE (iOCUM). By creating fusion images, we identified virus infected brain regions, mapped dopamine transporter and translocator protein expression, and traced innervation from the eye along the optic tract to the thalamus and superior colliculus using cholera toxin B. Fusion images allowed for precise anatomical identification of fluorescent signal in the detailed anatomical context provided by MR. Discussion: The possibility to anatomically map fluorescent signals on magnetic resonance (MR) images, widely used in clinical and preclinical neuroscience, would greatly benefit applications of optical imaging of mouse brain. These specific MR templates for cleared brains enable a broad range of neuroscientific applications integrating 3D optical brain imaging.
- Published
- 2024
- Full Text
- View/download PDF
3. Illuminating the complete ß-cell mass of the human pancreas- signifying a new view on the islets of Langerhans.
- Author
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Lehrstrand, Joakim, Davies, Wayne I. L., Hahn, Max, Korsgren, Olle, Alanentalo, Tomas, and Ahlgren, Ulf
- Subjects
ISLANDS of Langerhans ,THREE-dimensional imaging ,BLOOD sugar ,ISLANDS ,HOMEOSTASIS ,HUMAN beings - Abstract
Pancreatic islets of Langerhans play a pivotal role in regulating blood glucose homeostasis, but critical information regarding their mass, distribution and composition is lacking within a whole organ context. Here, we apply a 3D imaging pipeline to generate a complete account of the insulin-producing islets throughout the human pancreas at a microscopic resolution and within a maintained spatial 3D context. These data show that human islets are far more heterogenous than previously accounted for with regards to their size distribution and cellular make up. By deep tissue 3D imaging, this in-depth study demonstrates that 50% of the human insulin-expressing islets are virtually devoid of glucagon-producing α-cells, an observation with significant implications for both experimental and clinical research. The pancreatic islets of Langerhans play a pivotal role in regulating blood glucose homeostasis through the regulated secretion of the hormones insulin and glucagon. Here, the authors use deep tissue 3D imaging to re-construct the entire human pancreas at microscopic resolution and display previously unrecognized heterogeneities in the islet's cellularity with pre-clinical and clinical implications. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. SARS-CoV-2 infection induces hyaluronan production in vitro and hyaluronan levels in COVID-19 patients relate to morbidity and long-term lung impairment: a prospective cohort study.
- Author
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Hellman U, Rosendal E, Lehrstrand J, Henriksson J, Björsell T, Wennemo A, Hahn M, Österberg B, Dorofte L, Nilsson E, Forsell MNE, Smed-Sörensen A, Lange A, Karlsson MG, Ahlm C, Blomberg A, Cajander S, Ahlgren U, Lind A, Normark J, Överby AK, and Lenman A
- Subjects
- Humans, Male, Prospective Studies, Middle Aged, Female, Aged, Severity of Illness Index, Adult, COVID-19 metabolism, Hyaluronic Acid metabolism, Hyaluronic Acid blood, SARS-CoV-2, Lung pathology, Lung metabolism
- Abstract
We previously demonstrated that the lungs of deceased COVID-19 patients were filled with a clear hydrogel consisting of hyaluronan (HA). In this translational study, we investigated the role of HA at all stages of COVID-19 disease to map the consequences of elevated HA on morbidity and identify the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced HA production. A reduced alveolar surface area was observed in the lungs of deceased COVID-19 patients compared to healthy controls, as visualized by a 3D rendering of lung morphology using light-sheet fluorescence microscopy. We confirmed the presence of HA in lung biopsies and found large quantities of proinflammatory fragmented HA. The association of systemic HA in blood plasma and disease severity was assessed in patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1-5) and severe COVID-19 (WHO-CPS, 6-9) during the acute and convalescent phases and related to lung function. We found that systemic levels of HA were high during acute COVID-19 disease, remained elevated during convalescence, and were associated with a reduced diffusion capacity. In vitro 3D-lung models, differentiated from primary human bronchial epithelial cells, were used to study the effects of SARS-CoV-2 infection on HA metabolism, and transcriptomic analyses revealed a dysregulation of HA synthases and hyaluronidases, both contributing to increased HA in apical secretions. Furthermore, corticosteroid treatment reduced the inflammation and downregulated HA synthases. Our findings demonstrate that HA plays a role in COVID-19 morbidity and that sustained elevated HA concentrations may contribute to long-term respiratory impairment.IMPORTANCEThis study provides insights into the role of hyaluronan (HA) in the severity and long-term impact of COVID-19 on lung function. Through extensive morphological examination of lung tissues and a multicenter study, we identified that HA levels are significantly elevated in COVID-19 patients, correlating with a reduced lung diffusion capacity during convalescence. Using a 3D-lung model, we further uncovered how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection causes a dysregulated HA metabolism, leading to increased HA production. Our findings provide valuable insights into the pathogenesis of SARS-CoV-2 and suggest that targeting HA metabolism could offer new therapeutic avenues for managing COVID-19, particularly to prevent long-term lung impairment. Additionally, HA holds potential as a biomarker for predicting disease severity, which could guide personalized treatment strategies., Competing Interests: A. Lenman has received unconditional research support from Carl Bennet AB. A.S.-S. has received payments from Astra-Zeneca for Data and Safety Monitoring Board (DSMB) work on COVID-19 phase I/II/III clinical trials. S.C. has participated in DSMBs for Pfizer, Sobi, and MSD Merck. There are no patents, products in development, or marketed products associated with this research to declare. All other authors declare no conflicts of interest.
- Published
- 2024
- Full Text
- View/download PDF
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