Acute systemic LPS-exposure impairs perivascular CSF distribution in mice

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Manouchehrian, OscarLund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups (författare)

Acute systemic LPS-exposure impairs perivascular CSF distribution in mice

Artikel/kapitelEngelska2021

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2021-01-29
Springer Science and Business Media LLC,2021

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LIBRIS-ID:oai:lup.lub.lu.se:225aea8f-f102-4c76-9968-6f91e8ff3d4e
https://lup.lub.lu.se/record/225aea8f-f102-4c76-9968-6f91e8ff3d4eURI
https://doi.org/10.1186/s12974-021-02082-6DOI

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Språk:engelska
Sammanfattning på:engelska

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BACKGROUND: The exchange of cerebrospinal (CSF) and interstitial fluid is believed to be vital for waste clearance in the brain. The sleep-dependent glymphatic system, which is comprised of perivascular flow of CSF and is largely dependent on arterial pulsatility and astrocytic aquaporin-4 (AQP4) expression, facilitates much of this brain clearance. During the last decade, several observations have indicated that impaired glymphatic function goes hand in hand with neurodegenerative diseases. Since pathologies of the brain carry inflammatory components, we wanted to know how acute inflammation, e.g., with lipopolysaccharide (LPS) injections, would affect the glymphatic system. In this study, we aim to measure the effect of LPS on perivascular CSF distribution as a measure of glymphatic function.METHODS: Three hours after injection of LPS (1 mg/kg i.p.), C57bl/6 mice were (1) imaged for two CSF tracers, injected into cisterna magna, (2) transcardially perfused with buffer, or (3) used for physiological readouts. Tracer flow was imaged using a low magnification microscope on fixed brains, as well as using vibratome-cut slices for measuring tracer penetration in the brain. Cytokines, glial, and BBB-permeability markers were measured with ELISAs, Western blots, and immunohistochemistry. Cerebral blood flow was approximated using laser Doppler flowmetry, respiration and heart rate with a surgical monitor, and AQP4-polarization was quantified using confocal microscopy of immunolabeled brain sections.RESULTS: LPS-injections significantly lowered perivascular CSF tracer flow and penetration into the parenchyma. No differences in AQP4 polarization, cytokines, astroglial and BBB markers, cerebral blood flow, or respiration were detected in LPS-injected mice, although LPS did elevate cortical Iba1+ area and heart rate.CONCLUSIONS: This study reports another physiological response after acute exposure to the bacterial endotoxin LPS, namely the statistically significant decrease in perivascular distribution of CSF. These observations may benefit our understanding of the role of systemic inflammation in brain clearance.

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Ramos, MartaLund University,Lunds universitet,Cancer and matrix remodelling,Forskargrupper vid Lunds universitet,Glia-Immune Interactions,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine(Swepub:lu)ma1515ra (författare)
Bachiller, SaraLund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)sa2870ba (författare)
Lundgaard, IbenLund University,Lunds universitet,Glia-Immune Interactions,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine(Swepub:lu)ib4521lu (författare)
Deierborg, TomasLund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)expb-tol (författare)
NeuroinflammationForskargrupper vid Lunds universitet (creator_code:org_t)

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Ingår i:Journal of Neuroinflammation: Springer Science and Business Media LLC18:11742-2094

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Av författaren/redakt...: Manouchehrian, O ...; Ramos, Marta; Bachiller, Sara; Lundgaard, Iben; Deierborg, Tomas

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

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