دورية أكاديمية
أعرض في EDS

Posthemorrhagic hydrocephalus associates with elevated inflammation and CSF hypersecretion via activation of choroidal transporters.

التفاصيل البيبلوغرافية
العنوان: Posthemorrhagic hydrocephalus associates with elevated inflammation and CSF hypersecretion via activation of choroidal transporters.
المؤلفون: Lolansen SD; Department of Neuroscience, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark., Rostgaard N; Department of Neurosurgery, The Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Barbuskaite D; Department of Neuroscience, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark., Capion T; Department of Neurosurgery, The Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Olsen MH; Department of Neuroanaesthesiology, The Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Norager NH; Department of Neurosurgery, The Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Vilhardt F; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark., Andreassen SN; Department of Neuroscience, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark., Toft-Bertelsen TL; Department of Neuroscience, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark., Ye F; Department of Neurosurgery, University of Michigan, Ann Arbor, USA., Juhler M; Department of Neurosurgery, The Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Keep RF; Department of Neurosurgery, University of Michigan, Ann Arbor, USA., MacAulay N; Department of Neuroscience, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark. macaulay@sund.ku.dk.
المصدر: Fluids and barriers of the CNS [Fluids Barriers CNS] 2022 Aug 10; Vol. 19 (1), pp. 62. Date of Electronic Publication: 2022 Aug 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Biomed Central Country of Publication: England NLM ID: 101553157 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-8118 (Electronic) Linking ISSN: 20458118 NLM ISO Abbreviation: Fluids Barriers CNS Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Biomed Central
مواضيع طبية MeSH: Hydrocephalus*/surgery, Animals ; Biomarkers/metabolism ; Cerebral Hemorrhage/complications ; Choroid Plexus/metabolism ; Inflammation/metabolism ; Rats
مستخلص: Introduction: Posthemorrhagic hydrocephalus (PHH) often develops following hemorrhagic events such as intraventricular hemorrhage (IVH) and subarachnoid hemorrhage (SAH). Treatment is limited to surgical diversion of the cerebrospinal fluid (CSF) since no efficient pharmacological therapies are available. This limitation follows from our incomplete knowledge of the molecular mechanisms underlying the ventriculomegaly characteristic of PHH. Here, we aimed to elucidate the molecular coupling between a hemorrhagic event and the subsequent PHH development, and reveal the inflammatory profile of the PHH pathogenesis.
Methods: CSF obtained from patients with SAH was analyzed for inflammatory markers using the proximity extension assay (PEA) technique. We employed an in vivo rat model of IVH to determine ventricular size, brain water content, intracranial pressure, and CSF secretion rate, as well as for transcriptomic analysis. Ex vivo radio-isotope assays of choroid plexus transport were employed to determine the direct effect of choroidal exposure to blood and inflammatory markers, both with acutely isolated choroid plexus and after prolonged exposure obtained with viable choroid plexus kept in tissue culture conditions.
Results: The rat model of IVH demonstrated PHH and associated CSF hypersecretion. The Na + /K + -ATPase activity was enhanced in choroid plexus isolated from IVH rats, but not directly stimulated by blood components. Inflammatory markers that were elevated in SAH patient CSF acted on immune receptors upregulated in IVH rat choroid plexus and caused Na + /K + /2Cl - cotransporter 1 (NKCC1) hyperactivity in ex vivo experimental conditions.
Conclusions: CSF hypersecretion may contribute to PHH development, likely due to hyperactivity of choroid plexus transporters. The hemorrhage-induced inflammation detected in CSF and in the choroid plexus tissue may represent the underlying pathology. Therapeutic targeting of such pathways may be employed in future treatment strategies towards PHH patients.
(© 2022. The Author(s).)
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معلومات مُعتمدة: E-23565-03 The research council at Copenhagen University Hospital Rigshospitalet; R303-2018-3005 Lundbeckfonden; R276-2018-403 Lundbeckfonden; NNF17OC0024718 Novo Nordisk Fonden; NNF17OC0024718 Novo Nordisk Fonden; CF19-0056 Carlsbergfondet
فهرسة مساهمة: Keywords: Biomarkers; Cerebrospinal fluid; Choroid plexus; Immune response; Intraventricular hemorrhage; Posthemorrhagic hydrocephalus; Subarachnoid hemorrhage
المشرفين على المادة: 0 (Biomarkers)
تواريخ الأحداث: Date Created: 20220810 Date Completed: 20220812 Latest Revision: 20230916
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9367104
DOI: 10.1186/s12987-022-00360-w
PMID: 35948938
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-8118
DOI:10.1186/s12987-022-00360-w