Abstract
Longitudinal studies on brain pathology and assessment of therapeutic strategies rely on a fully mature adult brain to exclude confounds of cerebral developmental changes. Thus, knowledge about onset of adulthood is indispensable for discrimination of developmental phase and adulthood. We have performed a high-resolution longitudinal MRI study at 11.7T of male Wistar rats between 21days and six months of age, characterizing cerebral volume changes and tissue-specific myelination as a function of age. Cortical thickness reaches final value at 1month, while volume increases of cortex, striatum and whole brain end only after two months. Myelin accretion is pronounced until the end of the third postnatal month. After this time, continuing myelination increases in cortex are still seen on histological analysis but are no longer reliably detectable with diffusion-weighted MRI due to parallel tissue restructuring processes. In conclusion, cerebral development continues over the first three months of age. This is of relevance for future studies on brain disease models which should not start before the end of month 3 to exclude serious confounds of continuing tissue development.
Highlights
Brain development is a continuous process, which proceeds well after birth and even adolescence
As the tensor elements have been reported to be more sensitive than the fractional anisotropy (FA) alone which is a mathematical expression of the combination of the tensor elements (Bockhorst et al, 2008; Deo et al, 2006; Song et al, 2002), we have focused our analysis on λ∥and λ⊥
The combination of the different in vivo measurements in this study suggested cell density and myelination to be strongly responsible for changes in T2 and diffusion, respectively
Summary
Brain development is a continuous process, which proceeds well after birth and even adolescence. Most studies employing rats claim to use “young adults”, implying a fully matured brain parenchyma. The definition for “young adults” is diverse and ranges between two and four months old and body weight of 200 to 350 g. For longitudinal studies it is important to be able to discriminate between natural, development-dependent tissue changes and those alterations due to induced diseases or lesions. Tissues and microstructures mature at different paces, great care must be taken in choosing the age and observation period for the animal model of interest. Adolescence is understood as the time of transition between infancy and adulthood, despite a lack of clear and unambiguous boundaries between those stadiums.
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