Journal
AGING AND DISEASE
Volume 11, Issue 6, Pages 1407-1422Publisher
INT SOC AGING & DISEASE
DOI: 10.14336/AD.2020.0224
Keywords
neuronal excitation; brain extracellular space; interstitial fluid; tracer-based MRI; neurotransmitters
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Funding
- National Science Fund for Distinguished Young Scholars [61625102]
- Beijing Brain Initiative of Beijing Municipal Science & Technology Commission [Z181100001518004]
- Program for Training Capital Science and Technology Leading Talents [Z181100006318003]
- Peking University Clinical Scientist Program [BMU2019LCKXJ007]
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The drainage of brain interstitial fluid (ISF) has been observed to slow down following neuronal excitation, although the mechanism underlying this phenomenon is yet to be elucidated. In searching for the changes in the brain extracellular space (ECS) induced by electrical pain stimuli in the rat thalamus, significantly decreased effective diffusion coefficient (DECS) and volume fraction (a) of the brain ECS were shown, accompanied by the slowdown of ISF drainage. The morphological basis for structural changes in the brain ECS was local spatial deformation of astrocyte foot processes following neuronal excitation. We further studied aquaporin-4 gene (APQ4) knockout rats in which the changes of the brain ECS structure were reversed and found that the slowed DECS and ISF drainage persisted, confirming that the down-regulation of ISF drainage following neuronal excitation was mainly attributable to the release of neurotransmitters rather than to structural changes of the brain ECS. Meanwhile, the dynamic changes in the DECS were synchronized with the release and elimination processes of neurotransmitters following neuronal excitation. In conclusion, the downregulation of ISF drainage following neuronal excitation was found to be caused by the restricted diffusion in the brain ECS, and DECS mapping may be used to track the neuronal activity in the deep brain.
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