Abstract
The integrity of myelination is crucial for maintaining brain interstitial fluid (ISF) drainage in adults; however, the mechanism of ISF drainage with immature myelin in the developing brain remains unknown. In the present study, the ISF drainage from the caudate nucleus (Cn) to the ipsilateral cortex was studied at different developmental stages of the rat brain (P 10, 20, 30, 40, 60, 80, 10-80). The results show that the traced ISF drained to the cortex from Cn and to the thalamus in an opposite direction before P30. From P40, we found impeded drainage to the thalamus due to myelin maturation. This altered drainage was accompanied by enhanced cognitive and social functions, which were consistent with those in the adult rats. A significant difference in diffusion parameters was also demonstrated between the extracellular space (ECS) before and after P30. The present study revealed the alteration of ISF drainage regulated by myelin at different stages during development, indicating that a regional ISF homeostasis may be essential for mature psychological and cognitive functions.
Highlights
The integrity of myelination is crucial for maintaining brain interstitial fluid (ISF) drainage in adults; the mechanism of ISF drainage with immature myelin in the developing brain remains unknown
Dynamic changes of brain extracellular space (ECS) and ISF drainage with the development of myelination Using tracer-based magnetic resonance imaging (MRI), the traced brain ISF was found to drain from caudate nucleus (Cn) bi-directionally to the ipsilateral cortex and the adjacent thalamus in the P10, P20, and P30 groups
An initially highly connected ECS becomes compartmentalized by day 40 due to the maturation of myelin, which resulted in a more regular one-way ISF
Summary
The integrity of myelination is crucial for maintaining brain interstitial fluid (ISF) drainage in adults; the mechanism of ISF drainage with immature myelin in the developing brain remains unknown. These results indicate that myelin integrity determines the normal drainage of ISF within brain ECS [5,6,7]. A novel method of tracer-based magnetic resonance imaging (MRI) with ECS diffusion mapping (DECS-Mapping) technique [10,11] was used to study the ISF drainage at different post-natal developmental stages in rat brains (postnatal days [P] 10, 20, 30, 40, 60, 80, P10-80).
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