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Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis.
- Source :
-
Brain : a journal of neurology [Brain] 2007 May; Vol. 130 (Pt 5), pp. 1224-34. Date of Electronic Publication: 2007 Apr 02. - Publication Year :
- 2007
-
Abstract
- Neuromyelitis optica (NMO) is an inflammatory and necrotizing disease clinically characterized by selective involvement of the optic nerves and spinal cord. There has been a long controversy as to whether NMO is a variant of multiple sclerosis (MS) or a distinct disease. Recently, an NMO-specific antibody (NMO-IgG) was found in the sera from patients with NMO, and its target antigen was identified as aquaporin 4 (AQP4) water channel protein, mainly expressed in astroglial foot processes. However, the pathogenetic role of the AQP4 in NMO remains unknown. We did an immunohistopathological study on the distribution of AQP4, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), activated complement C9neo and immunoglobulins in the spinal cord lesions and medulla oblongata of NMO (n = 12), MS (n = 6), brain and spinal infarction (n = 7) and normal control (n = 8). The most striking finding was that AQP4 immunoreactivity was lost in 60 out of a total of 67 acute and chronic NMO lesions (90%), but not in MS plaques. The extensive loss of AQP4 accompanied by decreased GFAP staining was evident, especially in the active perivascular lesions, where immunoglobulins and activated complements were deposited. Interestingly, in those NMO lesions, MBP-stained myelinated fibres were relatively preserved despite the loss of AQP4 and GFAP staining. The areas surrounding the lesions in NMO had enhanced expression of AQP4 and GFAP, which reflected reactive gliosis. In contrast, AQP4 immunoreactivity was well preserved and rather strongly stained in the demyelinating MS plaques, and infarcts were also stained for AQP4 from the very acute phase of necrosis to the chronic stage of astrogliosis. In normal controls, AQP4 was diffusely expressed in the entire tissue sections, but the staining in the spinal cord was stronger in the central grey matter than in the white matter. The present study demonstrated that the immunoreactivities of AQP4 and GFAP were consistently lost from the early stage of the lesions in NMO, notably in the perivascular regions with complement and immunoglobulin deposition. These features in NMO were distinct from those of MS and infarction as well as normal controls, and suggest that astrocytic impairment associated with the loss of AQP4 and humoral immunity may be important in the pathogenesis of NMO lesions.
- Subjects :
- Adult
Aged
Aged, 80 and over
Astrocytes chemistry
Astrocytes pathology
Brain Infarction metabolism
Case-Control Studies
Complement Activation
Complement C9 analysis
Disease Progression
Female
Glial Fibrillary Acidic Protein analysis
Humans
Immunoglobulin G analysis
Immunohistochemistry
Infarction metabolism
Male
Medulla Oblongata pathology
Middle Aged
Multiple Sclerosis pathology
Myelin Basic Protein analysis
Neuromyelitis Optica pathology
Optic Nerve chemistry
Optic Nerve pathology
Spinal Cord blood supply
Spinal Cord pathology
Aquaporin 4 analysis
Medulla Oblongata chemistry
Multiple Sclerosis metabolism
Neuromyelitis Optica metabolism
Spinal Cord chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2156
- Volume :
- 130
- Issue :
- Pt 5
- Database :
- MEDLINE
- Journal :
- Brain : a journal of neurology
- Publication Type :
- Academic Journal
- Accession number :
- 17405762
- Full Text :
- https://doi.org/10.1093/brain/awm047