Mapping of neuroinflammation-induced hypoxia in the spinal cord using optoacoustic imaging

Acta Neuropathologica Communications

B. Thomas Bäckström¹  Tekla Maria Kylkilahti²  Marta Ramos-Vega²  Iben Lundgaard²  Pontus Kjellman³  Chris Denis Madsen³  Mihail Ivilinov Todorov⁴  Ali Ertürk⁴ 

[1] Department of Clinical Sciences, Department of Neurosurgery, Lund University;Department of Experimental Medical Science, Lund University;Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University;Institute for Tissue Engineering and Regenerative Medicine (ITERM), Helmholtz Zentrum München;

关键词: Neuroinflammation;    Hypoxia;    Optoacoustic imaging;    Light sheet fluorescence microscopy;    EAE;    Multiple sclerosis;   

DOI  :  10.1186/s40478-022-01337-4

来源: DOAJ

【 摘 要 】

Abstract Recent studies suggest that metabolic changes and oxygen deficiency in the central nervous system play an important role in the pathophysiology of multiple sclerosis (MS). In our present study, we investigated the changes in oxygenation and analyzed the vascular perfusion of the spinal cord in a rodent model of MS. We performed multispectral optoacoustic tomography of the lumbar spinal cord before and after an oxygen enhancement challenge in mice with experimental autoimmune encephalomyelitis (EAE), a model for MS. In addition, mice were transcardially perfused with lectin to label the vasculature and their spinal columns were optically cleared, followed by light sheet fluorescence microscopy. To analyze the angioarchitecture of the intact spine, we used VesSAP, a novel deep learning-based framework. In EAE mice, the spinal cord had lower oxygen saturation and hemoglobin concentration compared to healthy mice, indicating compromised perfusion of the spinal cord. Oxygen administration reversed hypoxia in the spinal cord of EAE mice, although the ventral region remained hypoxic. Additionally, despite the increased vascular density, we report a reduction in length and complexity of the perfused vascular network in EAE. Taken together, these findings highlight a new aspect of neuroinflammatory pathology, revealing a significant degree of hypoxia in EAE in vivo that is accompanied by changes in spinal vascular perfusion. The study also introduces optoacoustic imaging as a tractable technique with the potential to further decipher the role of hypoxia in EAE and to monitor it in MS patients.

【 授权许可】

Unknown