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      Respiratory brain impulse propagation in focal epilepsy

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          Abstract

          Respiratory brain pulsations pertaining to intra-axial hydrodynamic solute transport are markedly altered in focal epilepsy. We used optical flow analysis of ultra-fast functional magnetic resonance imaging (fMRI) data to investigate the velocity characteristics of respiratory brain impulse propagation in patients with focal epilepsy treated with antiseizure medication (ASM) (medicated patients with focal epilepsy; ME, n = 23), drug-naïve patients with at least one seizure (DN, n = 19) and matched healthy control subjects (HC, n = 75). We detected in the two patient groups (ME and DN) several significant alterations in the respiratory brain pulsation propagation velocity, which showed a bidirectional change dominated by a reduction in speed. Furthermore, the respiratory impulses moved more in reversed or incoherent directions in both patient groups vs. the HC group. The speed reductions and directionality changes occurred in specific phases of the respiratory cycle. In conclusion, irrespective of medication status, both patient groups showed incoherent and slower respiratory brain impulses, which may contribute to epileptic brain pathology by hindering brain hydrodynamics.

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          A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β.

          Because it lacks a lymphatic circulation, the brain must clear extracellular proteins by an alternative mechanism. The cerebrospinal fluid (CSF) functions as a sink for brain extracellular solutes, but it is not clear how solutes from the brain interstitium move from the parenchyma to the CSF. We demonstrate that a substantial portion of subarachnoid CSF cycles through the brain interstitial space. On the basis of in vivo two-photon imaging of small fluorescent tracers, we showed that CSF enters the parenchyma along paravascular spaces that surround penetrating arteries and that brain interstitial fluid is cleared along paravenous drainage pathways. Animals lacking the water channel aquaporin-4 (AQP4) in astrocytes exhibit slowed CSF influx through this system and a ~70% reduction in interstitial solute clearance, suggesting that the bulk fluid flow between these anatomical influx and efflux routes is supported by astrocytic water transport. Fluorescent-tagged amyloid β, a peptide thought to be pathogenic in Alzheimer's disease, was transported along this route, and deletion of the Aqp4 gene suppressed the clearance of soluble amyloid β, suggesting that this pathway may remove amyloid β from the central nervous system. Clearance through paravenous flow may also regulate extracellular levels of proteins involved with neurodegenerative conditions, its impairment perhaps contributing to the mis-accumulation of soluble proteins.
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            Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images

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              Sleep drives metabolite clearance from the adult brain.

              The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.
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                Author and article information

                Contributors
                Ahmed.Elabasy@oulu.fi
                Mia.suhonen@oulu.fi
                vesa.kiviniemi@oulu.fi
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                30 March 2023
                30 March 2023
                2023
                : 13
                : 5222
                Affiliations
                [1 ]GRID grid.10858.34, ISNI 0000 0001 0941 4873, Center for Machine Vision and Signal Analysis, , University of Oulu, ; 90014 Oulu, Finland
                [2 ]GRID grid.10858.34, ISNI 0000 0001 0941 4873, Medical Imaging, Physics and Technology, , University of Oulu, ; 90029 Oulu, Finland
                [3 ]GRID grid.412326.0, ISNI 0000 0004 4685 4917, Oulu Functional NeuroImaging, Diagnostic Radiology, Medical Research Center/HTS, , Oulu University Hospital, ; 90029 Oulu, Finland
                [4 ]GRID grid.10858.34, ISNI 0000 0001 0941 4873, Research Unit of Clinical Neuroscience, Neurology, University of Oulu, ; 90029 Oulu, Finland
                [5 ]GRID grid.412326.0, ISNI 0000 0004 4685 4917, Neurocenter, Neurology, Oulu University Hospital, Member of ERN EpiCARE, ; 90029 Oulu, Finland
                [6 ]GRID grid.412326.0, ISNI 0000 0004 4685 4917, MRC, Oulu University Hospital, ; 90029 Oulu, Finland
                [7 ]GRID grid.412326.0, ISNI 0000 0004 4685 4917, Clinical Neurophysiology, Oulu University Hospital, , 90029 OYS, ; Oulu, Finland
                Article
                32271
                10.1038/s41598-023-32271-7
                10063583
                36997658
                2df3ee7a-90cf-449d-b3a1-5ed533fd4269
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 January 2023
                : 24 March 2023
                Funding
                Funded by: Epilepsy Research Foundation
                Funded by: Finnish Cultural Foundation, North Ostrobothnia Regional Fund
                Funded by: Tauno Tönning Foundation
                Funded by: The University of Oulu Scholarship Foundation
                Funded by: Medical Research Center (MRC) -Oulu
                Funded by: Maire Taponen Foundation sr
                Funded by: Finnish Brain Foundation sr
                Funded by: Instrumentarium Science Foundation sr
                Funded by: Orion Research Foundation
                Funded by: The Finnish Medical Foundation
                Funded by: Pohjois-Suomen Terveydenhuollon tukisäätiö
                Funded by: Finnish Academy
                Award ID: 275352
                Award Recipient :
                Funded by: Jane and Aatos Erkko Foundation
                Award ID: 1
                Award Recipient :
                Funded by: KEVO grants from Oulu University Hospital
                Categories
                Article
                Custom metadata
                © The Author(s) 2023

                Uncategorized
                neurology,epilepsy
                Uncategorized
                neurology, epilepsy

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