Blood-brain barrier leakage of blood proteins in idiopathic normal pressure hydrocephalus

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Nyckelord

Blood-brain barrier dysfunction

Fibrinogen/fibrin extravasation

Dysfunction of capillaries

Impaired neurovascular unit

Astrogliosis

Neurodegeneration

neurovascular unit

aquaporin-4

fibrinogen

disease

health

flow

fibrinolysis

permeability

association

management

Neurosciences & Neurology

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