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Astrogliosis and impaired aquaporin‐4 and dystrophin systems in idiopathic normal pressure hydrocephalus
Abstract
Aims: Idiopathic normal pressure hydrocephalus (iNPH) is one subtype of dementia that may improve following drainage of cerebrospinal fluid (CSF). This prospective observational study explored whether expression of the water channel aquaporin‐4 (AQP4) and the anchoring molecule dystrophin 71 (Dp71) are altered at astrocytic perivascular endfeet and in adjacent neuropil of iNPH patient. Observations were related to measurements of pulsatile and static intracranial pressure (ICP). Methods: The study included iNPH patients undergoing overnight monitoring of the pulsatile/static ICP in whom a biopsy was taken from the frontal cerebral cortex during placement of the ICP sensor. Reference (Ref) biopsies were sampled from 13 patients who underwent brain surgery for epilepsy, tumours or cerebral aneurysms. The brain tissue specimens were examined by light microscopy, immunohistochemistry, densitometry and morphometry. Results: iNPH patients responding to surgery ( n = 44) had elevated pulsatile ICP, indicative of impaired intracranial compliance. As compared to the Ref patients, the cortical biopsies of iNPH patients revealed prominent astrogliosis and reduced expression of AQP4 and Dp71 immunoreactivities in the astrocytic perivascular endfeet and in parts of the adjacent neuropil. There was a significant correlation between degree of astrogliosis and reduction of AQP4 and Dp71 at astrocytic perivascular endfeet. Conclusions: Idiopathic normal pressure hydrocephalus patients responding to CSF diversion present with abnormal pulsatile ICP, indicative of impaired intracranial compliance. A main histopathological finding was astrogliosis and reduction of AQP4 and of Dp71 in astrocytic perivascular endfeet. We propose that the altered AQP4 and Dp71 complex contributes to the subischaemia prevalent in the brain tissue of iNPH.
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“AQP4 density and its anchoring protein dystrophin 71 have been found to be reduced at astrocytic end feet in iNPH (73).”
From Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. (2018) · cites this paper as [73]
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Metadata
- Authors
- Eide, P. K., & Hansson, H. ‐.
- Affiliations
- Oslo University Hospital (NO)
- University of Gothenburg (SE)
- Corresponding author
- Eide, P. K.
- Venue
- Neuropathology and Applied Neurobiology
- Publisher
- Wiley
- Published
- 2017-07-19
- Volume
- 44
- Issue
- 5
- Pages
- 474-490
- ISSN
- 0305-1846 (ISSN-L)
- 1365-2990
- OpenAlex
- W2664710281
- Cited by
- 119
- References
- 64
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 14 · 2023: 18 · 2022: 18 · 2021: 13 · 2020: 7 · 2019: 9 · 2018: 7 · 2017: 2
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropathology and Applied Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Stiftelserna Wilhelm och Martina Lundgrens
- Topics
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- idiopathic normal pressure hydrocephalus, astrocyte activation, aquaporin-4, intracranial compliance, cerebrospinal fluid drainage
- MeSH terms
- Aged, Female, Gliosis, Humans, Hydrocephalus, Normal Pressure, Male, Middle Aged, Dystrophin, Aquaporin 4
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