Local diffusion in the extracellular space of the brain

Tønnesen, Jan; Hrabětová, Sabina; Soria, F.

doi:10.1016/j.nbd.2022.105981

Cited by 21 publications

(10 citation statements)

References 128 publications

(198 reference statements)

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“…Recent studies show that ECM's role is not restricted to the neuronal soma. It regulates synaptic plasticity by regulating neurotransmitters' diffusibility in and beyond the synaptic cleft [39][40][41], AMPAR receptor mobility [42], and physiological remodeling of the ECM in the hippocampus can increase plasticity [43].…”

Section: Introductionmentioning

confidence: 99%

Novel extracellular matrix architecture on excitatory neurons revealed by HaloTag-HAPLN1

Sterin,

Niazi,

Kim

et al. 2024

Preprint

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The brain's extracellular matrix (ECM) regulates neuronal plasticity and animal behavior. ECM staining shows an aggregated pattern in a net-like structure around a subset of neurons and diffuse staining in the interstitial matrix. However, understanding the structural features of ECM deposition across various neuronal types and subcellular compartments remains limited. To visualize the organization pattern and assembly process of the hyaluronan-scaffolded ECM in the brain, we fused a HaloTag to HAPLN1, which links hyaluronan and proteoglycans. Expression or application of the probe enables us to identify spatial and temporal regulation of ECM deposition and heterogeneity in ECM aggregation among neuronal populations. Dual-color birthdating shows the ECM assembly process in culture and in vivo. Sparse expression in vivo reveals novel forms of ECM architecture around excitatory neurons and developmentally regulated dendritic ECM. Overall, our study uncovers extensive structural features of the brain's ECM, suggesting diverse roles in regulating neuronal plasticity.

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Section: Introductionmentioning

confidence: 99%

Novel extracellular matrix architecture on excitatory neurons revealed by HaloTag-HAPLN1

Sterin,

Niazi,

Kim

et al. 2024

Preprint

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“…Among the several factors at work, a greater diffusion within the extracellular space of the different species 15 , 16 , notably to the hemisphere contralateral to the injection, could play a role and even lead to leakage to the peripheral organs. We thus hypothesised that restricting vector diffusion after injection could lead to (i) greater, more specific lesions of the nigrostriatal pathway and (ii) decreased leakage towards the periphery.…”

Section: Introductionmentioning

confidence: 99%

In vivo bioluminescence imaging of the intracerebral fibroin-controlled AAV-α-synuclein diffusion for monitoring the central nervous system and peripheral expression

Mazzocco,

Genevois,

et al. 2024

Sci Rep

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Among the several animal models of α-synucleinopathies, the well-known viral vector-mediated delivery of wild-type or mutated (A53T) α-synuclein requires new tools to increase the lesion in mice and follow up in vivo expression. To this end, we developed a bioluminescent expression reporter of the human A53T-α-synuclein gene using the NanoLuc system into an AAV2/9, embedded or not in a fibroin solution to stabilise its expression in space and time. We first verified the expression of the fused protein in vitro on transfected cells by bioluminescence and Western blotting. Next, two groups of C57Bl6Jr mice were unilaterally injected with the AAV-NanoLuc-human-A53T-α-synuclein above the substantia nigra combined (or not) with fibroin. We first show that the in vivo cerebral bioluminescence signal was more intense in the presence of fibroin. Using immunohistochemistry, we find that the human-A53T-α-synuclein protein is more restricted to the ipsilateral side with an overall greater magnitude of the lesion when fibroin was added. However, we also detected a bioluminescence signal in peripheral organs in both conditions, confirmed by the presence of viral DNA corresponding to the injected AAV in the liver using qPCR.

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“…The ISS is a component of the larger extracellular space; this larger space includes the ventricles and vascular spaces; often the term 'extracellular space' is loosely used as a synonym for the ISS. Although the ISS is critical for neurological function it has not received much attention but recently interest has increased [1][2][3][4]. Some of this attention followed the identification of a glymphatic system [5,6], which resurfaced a longstanding debate about transport modes in the ISS.…”

Section: Introductionmentioning

confidence: 99%

Sheet and void porous media models for brain interstitial space

Nicholson

2023

J. R. Soc. Interface.

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The interstitial space (ISS) component of brain extracellular space resembles an unconsolidated porous medium. Previous analysis of the diffusion of small molecules in this domain shows that the typical porosity is 0.2 and typical tortuosity 1.6. An ensemble of cubic cells separated by uniform sheets of ISS cannot generate the measured tortuosity, even if some of the tortuosity value is attributed to interstitial viscosity, so more complex models are needed. Here two models are analysed: the corner cubic void (CCV) and the edge tunnel void (ETV). Both models incorporate dead spaces formed from local expansions of the ISS to increase geometrical tortuosity. Using Monte Carlo simulation of diffusion it is found that in the range of normal porosities, the square of the tortuosity is a linear function of the ratio of void to sheet volumes for the CCV model and this model can generate the experimentally observed tortuosities. For abnormally high porosities, however, the linear relation fails. The ETV model shows a quartic functional relation and can only generate the observed tortuosity if interstitial viscosity is present. The CCV model is used to analyse the recently described changes in porosity between asleep and awake brain states.

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Local diffusion in the extracellular space of the brain

Cited by 21 publications

References 128 publications

Novel extracellular matrix architecture on excitatory neurons revealed by HaloTag-HAPLN1

Novel extracellular matrix architecture on excitatory neurons revealed by HaloTag-HAPLN1

In vivo bioluminescence imaging of the intracerebral fibroin-controlled AAV-α-synuclein diffusion for monitoring the central nervous system and peripheral expression

Sheet and void porous media models for brain interstitial space

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