Per Kristian Eide1, Hans-Arne Hansson2. 1. Department of Neurosurgery, Oslo University Hospital - Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: p.k.eide@medisin.uio.no. 2. Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
Abstract
AIM: Idiopathic normal pressure hydrocephalus (iNPH) is one subtype of dementia characterized by cerebrospinal fluid (CSF) disturbance, but with unknown cause. We recently reported that frontal cortex biopsies of iNPH patients disclosed degenerative alterations of the capillary basement membrane, including degenerated pericyte processes. Given that pericyte degeneration is associated with blood-brain barrier (BBB) dysfunction, the present study was undertaken to examine whether BBB leakage of blood proteins can be revealed by light microscopy (LM) immunohistochemistry in iNPH. METHODS: The study included cortical brain tissue specimens from 14 reference (REF) subjects undergoing neurosurgery for epilepsy, aneurysm or tumor, and 45 iNPH patients. Dysfunction of the BBB was measured semi-quantitatively as area percentage extravasated fibrin(ogen) in cerebral cortical layers I, II and III. The degree of fibrin(ogen) extravasation was also correlated with expression of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), dystrophin 71 (Dp71) and Cluster of Differentiation 68 (CD68). RESULTS: The study disclosed extravasation of fibrin(ogen) in 4/14 REF subjects and in 45/45 iNPH patients, the percentage area of fibrin(ogen) was significantly higher in iNPH than REF cortical specimens. Diffuse, less prominent fibrin(ogen) extravasation was seen in the subcortical white matter of one iNPH individual. Increasing degree of fibrinogen extravasation in cerebral cortex was significantly associated with increasing degree of astrogliosis and with reduced expression of perivascular AQP4 and Dp71. CONCLUSIONS: The present results provide evidence of BBB dysfunction in iNPH. The BBB leakage of blood proteins may render for impaired neurovascular units in iNPH patients.
AIM: Idiopathic normal pressure hydrocephalus (iNPH) is one subtype of dementia characterized by cerebrospinal fluid (CSF) disturbance, but with unknown cause. We recently reported that frontal cortex biopsies of iNPH patients disclosed degenerative alterations of the capillary basement membrane, including degenerated pericyte processes. Given that pericyte degeneration is associated with blood-brain barrier (BBB) dysfunction, the present study was undertaken to examine whether BBB leakage of blood proteins can be revealed by light microscopy (LM) immunohistochemistry in iNPH. METHODS: The study included cortical brain tissue specimens from 14 reference (REF) subjects undergoing neurosurgery for epilepsy, aneurysm or tumor, and 45 iNPH patients. Dysfunction of the BBB was measured semi-quantitatively as area percentage extravasated fibrin(ogen) in cerebral cortical layers I, II and III. The degree of fibrin(ogen) extravasation was also correlated with expression of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), dystrophin 71 (Dp71) and Cluster of Differentiation 68 (CD68). RESULTS: The study disclosed extravasation of fibrin(ogen) in 4/14 REF subjects and in 45/45 iNPH patients, the percentage area of fibrin(ogen) was significantly higher in iNPH than REF cortical specimens. Diffuse, less prominent fibrin(ogen) extravasation was seen in the subcortical white matter of one iNPH individual. Increasing degree of fibrinogen extravasation in cerebral cortex was significantly associated with increasing degree of astrogliosis and with reduced expression of perivascular AQP4 and Dp71. CONCLUSIONS: The present results provide evidence of BBB dysfunction in iNPH. The BBB leakage of blood proteins may render for impaired neurovascular units in iNPH patients.
Authors: Per Kristian Eide; Aslan Lashkarivand; Åsmund Aleksander Hagen-Kersten; Øivind Gjertsen; Bård Nedregaard; Ruth Sletteberg; Grethe Løvland; Svein Are Sirirud Vatnehol; Are Hugo Pripp; Lars Magnus Valnes; Geir Ringstad Journal: Front Neurol Date: 2022-04-06 Impact factor: 4.086
Authors: Phillip A Bonney; Robert G Briggs; Kevin Wu; Wooseong Choi; Anadjeet Khahera; Brandon Ojogho; Xingfeng Shao; Zhen Zhao; Matthew Borzage; Danny J J Wang; Charles Liu; Darrin J Lee Journal: Front Aging Neurosci Date: 2022-04-28 Impact factor: 5.750
Authors: Per K Eide; Espen Mariussen; Hilde Uggerud; Are H Pripp; Aslan Lashkarivand; Bjørnar Hassel; Hege Christensen; Markus Herberg Hovd; Geir Ringstad Journal: JCI Insight Date: 2021-05-10