Contributions
Abstract: P1060
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Introduction: Experimental autoimmune encephalomyelitis (EAE) is widely used as a model of multiple sclerosis (MS). However, the development of cerebral focal lesions in EAE is quite inconsistent and hence experimental assessment of lesion pathogenesis and progression is difficult.
Objectives: To develop a model of focal brain lesion induction in EAE using focused ultrasound (FUS) and to monitor lesion formation and development with MRI and magnetic resonance elastography (MRE).
Aims: To analyse whether FUS induced blood brain barrier disruption (BBBD) increases the likelihood of lesion occurrence in the sonicated parenchyma and to evaluate, if early inflammatory changes can be visualized with MRI and MRE. We hypothesized that FUS-BBBD facilitates the influx of inflammatory cells into the brain and thus promotes lesion formation. We also hypothesized that early inflammation interferes with the geometrical lattice of the brain, rendering lesions detectable with MRE.
Methods: EAE was induced in female C57BL/6 mice using myelin oligodendrocyte glycoprotein (MOG) peptide. FUS was performed 6, 7 and 9 days after immunization in subgroups of 4 animals each and in controls. MRI and MRE were acquired 14 and 21 days after induction on a 7T scanner. Post-mortem histopathology was assessed.
Results: Seven animals presented with T2w hyperintensities in the sonicated hemisphere. Histopathology revealed foci of activated microglia/macrophages in the sonicated right hemisphere of seven EAE animals. Five of the T2w hyperintensities could be co-localized to foci of activated microglia/macrophages. These T2w conspicuities tended to be softer and less viscous than corresponding normal brain tissue. Moreover, the MRE parameters of the right sonicated and the left normal cortex were relevantly different in EAE-animals (mean stiffness right sonicated cortex 6.6 kPa vs. left cortex 7.5 kPa). Larger cellular infiltrates or demyelination were absent. Controls neither showed MR signal alterations nor inflammatory histological changes.
Conclusions: Focal activation of microglia/macrophages in the absence of lymphocytic infiltration appears to be an early step in lesion formation, consistent with recent human findings. Ipsilateral hemispheric softening consistent with more diffuse and subtle edematous changes were also observed. We provide evidence for controlled lesion induction in EAE using FUS-BBBD.
Disclosure: Katharina Schregel received funding from the German Research Foundation (DFG, SCHR 1542/1-1).
Caroline Baufeld has nothing to disclose.
Miklos Palotai has nothing to disclose.
Roberta Meroni has nothing to disclose.
Paolo Fiorina has nothing to disclose.
Jens Wuerfel is CEO of MIAC AG Basel, Switzerland. He served on scientific advisory boards of Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche. He is or was supported by grants of the EU (Horizon2020), German Federal Ministries of Education and Research (BMBF) and of Economic Affairs and Energy (BMWI).
Yonghzi Zang has nothing to disclose.
Ralph Sinkus has nothing to disclose.
Samuel Patz has nothing to disclose.
Nathan McDannold has nothing to disclose.
P. Jason White has nothing to disclose.
Charles R.G. Guttmann has nothing to disclose that could constitute a conflict of interest for this work. Dr. Guttmann has received research funding from Sanofi, the National Multiple Sclerosis Society, and the International Progressive Multiple Sclerosis Alliance.
Abstract: P1060
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Introduction: Experimental autoimmune encephalomyelitis (EAE) is widely used as a model of multiple sclerosis (MS). However, the development of cerebral focal lesions in EAE is quite inconsistent and hence experimental assessment of lesion pathogenesis and progression is difficult.
Objectives: To develop a model of focal brain lesion induction in EAE using focused ultrasound (FUS) and to monitor lesion formation and development with MRI and magnetic resonance elastography (MRE).
Aims: To analyse whether FUS induced blood brain barrier disruption (BBBD) increases the likelihood of lesion occurrence in the sonicated parenchyma and to evaluate, if early inflammatory changes can be visualized with MRI and MRE. We hypothesized that FUS-BBBD facilitates the influx of inflammatory cells into the brain and thus promotes lesion formation. We also hypothesized that early inflammation interferes with the geometrical lattice of the brain, rendering lesions detectable with MRE.
Methods: EAE was induced in female C57BL/6 mice using myelin oligodendrocyte glycoprotein (MOG) peptide. FUS was performed 6, 7 and 9 days after immunization in subgroups of 4 animals each and in controls. MRI and MRE were acquired 14 and 21 days after induction on a 7T scanner. Post-mortem histopathology was assessed.
Results: Seven animals presented with T2w hyperintensities in the sonicated hemisphere. Histopathology revealed foci of activated microglia/macrophages in the sonicated right hemisphere of seven EAE animals. Five of the T2w hyperintensities could be co-localized to foci of activated microglia/macrophages. These T2w conspicuities tended to be softer and less viscous than corresponding normal brain tissue. Moreover, the MRE parameters of the right sonicated and the left normal cortex were relevantly different in EAE-animals (mean stiffness right sonicated cortex 6.6 kPa vs. left cortex 7.5 kPa). Larger cellular infiltrates or demyelination were absent. Controls neither showed MR signal alterations nor inflammatory histological changes.
Conclusions: Focal activation of microglia/macrophages in the absence of lymphocytic infiltration appears to be an early step in lesion formation, consistent with recent human findings. Ipsilateral hemispheric softening consistent with more diffuse and subtle edematous changes were also observed. We provide evidence for controlled lesion induction in EAE using FUS-BBBD.
Disclosure: Katharina Schregel received funding from the German Research Foundation (DFG, SCHR 1542/1-1).
Caroline Baufeld has nothing to disclose.
Miklos Palotai has nothing to disclose.
Roberta Meroni has nothing to disclose.
Paolo Fiorina has nothing to disclose.
Jens Wuerfel is CEO of MIAC AG Basel, Switzerland. He served on scientific advisory boards of Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche. He is or was supported by grants of the EU (Horizon2020), German Federal Ministries of Education and Research (BMBF) and of Economic Affairs and Energy (BMWI).
Yonghzi Zang has nothing to disclose.
Ralph Sinkus has nothing to disclose.
Samuel Patz has nothing to disclose.
Nathan McDannold has nothing to disclose.
P. Jason White has nothing to disclose.
Charles R.G. Guttmann has nothing to disclose that could constitute a conflict of interest for this work. Dr. Guttmann has received research funding from Sanofi, the National Multiple Sclerosis Society, and the International Progressive Multiple Sclerosis Alliance.