Astrogliosis and impaired aquaporin‐4 and dystrophin systems in idiopathic normal pressure hydrocephalus

Jun 20, 2017Neuropathology and applied neurobiology

Brain support cell changes and water channel problems in normal pressure hydrocephalus

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Abstract

iNPH patients responding to surgery (n = 44) exhibited elevated pulsatile intracranial pressure.

Cortical biopsies from iNPH patients showed prominent astrogliosis compared to reference patients.
Reduced expression of the water channel aquaporin-4 (AQP4) and the anchoring molecule dystrophin 71 (Dp71) was observed in astrocytic perivascular endfeet of iNPH patients.
A significant correlation was found between the degree of astrogliosis and the reduction of AQP4 and Dp71 in these areas.
Abnormal pulsatile intracranial pressure suggests impaired intracranial compliance in iNPH patients.
Altered levels of AQP4 and Dp71 may contribute to subischaemia in the brain tissue of iNPH.

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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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Astrogliosis and impaired aquaporin‐4 and dystrophin systems in idiopathic normal pressure hydrocephalus

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