Abstract
The biomechanical properties of brain tissue are altered by histopathological changes due to neurodegenerative diseases like Parkinson's disease (PD). Such alterations can be measured by magnetic resonance elastography (MRE) as a non-invasive technique to determine viscoelastic parameters of the brain. Until now, the correlation between histopathological mechanisms and observed alterations in tissue viscoelasticity in neurodegenerative diseases is still not completely understood. Thus, the objective of this study was to evaluate (1) the validity of MRE to detect viscoelastic changes in small and specific brain regions: the substantia nigra (SN), midbrain and hippocampus in a mouse model of PD, and (2) if the induced dopaminergic neurodegeneration and inflammation in the SN is reflected by local changes in viscoelasticity. Therefore, MRE measurements of the SN, midbrain and hippocampus were performed in adult female mice before and at five time points after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin hydrochloride (MPTP) treatment specifically lesioning dopaminergic neurons in the SN. At each time point, additional mice were utilized for histological analysis of the SN. After treatment cessation, we observed opposed viscoelastic changes in the midbrain, hippocampus and SN with the midbrain showing a gradual rise and the hippocampus a distinct transient increase of viscous and elastic parameters, while viscosity and–to a lesser extent—elasticity in the SN decreased over time. The decrease in viscosity and elasticity in the SN was paralleled by a reduced number of neurons due to the MPTP-induced neurodegeneration. In conclusion, MRE is highly sensitive to detect local viscoelastic changes in specific and even small brain regions. Moreover, we confirmed that neuronal cells likely constitute the backbone of the adult brain mainly accounting for its viscoelasticity. Therefore, MRE could be established as a new potential instrument for clinical evaluation and diagnostics of neurodegenerative diseases.
Highlights
The macroscopic biomechanical properties of in vivo brain tissue are influenced by the cellular composition of the brain given by the number of neurons and glial cells as well as their interactions with the extracellular matrix [1,2,3]
We demonstrate how viscosity and elasticity in various brain areas change in response to MPTP treatment and that the significant reduction of dopaminergic neurons in the substantia nigra (SN) in a mouse model for a neurodegenerative disease is reflected in the decrease of viscosity and–to a lesser extent–elasticity
The neurotoxin MPTP primarily affects dopaminergic neurons and is an established animal model for the histopathology seen in Parkinson's disease (PD) patients [19,20]
Summary
The macroscopic biomechanical properties of in vivo brain tissue are influenced by the cellular composition of the brain given by the number of neurons and glial cells as well as their interactions with the extracellular matrix [1,2,3]. This composition varies in diverse brain regions and under pathological conditions so that histological differences may be reflected in the biomechanical properties of tissue and can be represented in viscoelastic quantities. G'' gives information about the viscous, dampening properties of the tissue, which depend on the geometry of the network including bonds and branching
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