Abstract：
:It is well established that the binding of pathogenic aquaporin-4 (AQP4)-specific autoantibodies to astrocytes may initiate a cascade of events culminating in the destruction of these cells and in the formation of large tissue-destructive lesions typical for patients with neuromyelitis optica spectrum disorders (NMOSD). To date, not a single experimental study has shown that the systemic presence of the antibody alone can induce any damage to the central nervous system (CNS), while pathological studies on brains of NMOSD patients suggested that there might be ways for antibody entry and subsequent tissue damage. Here, we systemically applied a highly pathogenic, monoclonal antibody with high affinity to AQP4 over prolonged period of time to rats, and show that AQP4-abs can enter the CNS on their own, via circumventricular organs and meningeal or parenchymal blood vessels, that these antibodies initiate the formation of radically different lesions with AQP4 loss, depending on their mode and site of entry, and that lesion formation is much more efficient in the presence of encephalitogenic T-cell responses. We further demonstrate that the established tissue-destructive lesions trigger the formation of additional lesions by short and far reaching effects on blood vessels and their branches, and that AQP4-abs have profound effects on the AQP4 expression in peripheral tissues which counter-act possible titer loss by antibody absorption outside the CNS. Cumulatively, these data indicate that directly induced pathological changes caused by AQP4-abs inside and outside the CNS are efficient drivers of disease evolution in seropositive organisms.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Hillebrand S,Schanda K,Nigritinou M,Tsymala I,Böhm D,Peschl P,Takai Y,Fujihara K,Nakashima I,Misu T,Reindl M,Lassmann H,Bradl Mdoi
10.1007/s00401-018-1950-8subject
Has Abstractpub_date
2019-03-01 00:00:00pages
467-485issue
3eissn
0001-6322issn
1432-0533pii
10.1007/s00401-018-1950-8journal_volume
137pub_type
杂志文章abstract：:In search of novel genes associated with glioma pathogenesis, we have previously shown frequent deletions of the KIAA1797/FOCAD gene in malignant gliomas, and a tumor suppressor function of the encoded focadhesin impacting proliferation and migration of glioma cells in vitro and in vivo. Here, we examined an associati...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-019-02067-z
更新日期：2020-01-01 00:00:00
abstract：:Pilocytic astrocytomas are the most common astrocytic tumors of childhood and differ clinically and histopathologically from those astrocytomas that affect adults. Studies of adult astrocytic tumors have revealed allelic losses on chromosomes 10, 17p, 19q and alterations in the epidermal growth factor receptor (EGFR) ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00454903
更新日期：1993-01-01 00:00:00
abstract：:Round granulated body (RGB) and eosinophilic hyaline droplets (EHDs) have been described as cytoplasmic inclusions of certain astrocytic tumors. In the previous literature, however, these inclusions have been described using various terms or regarded as nosologically the same entity. Light microscopically, RGB appeare...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00296486
更新日期：1994-01-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the aggregation of ubiquitinated proteins in affected motor neurons. Recent studies have identified several new molecular constituents of ALS-linked cellular aggregates, including FUS, TDP-43, OPTN, UBQLN2 and the translational product...
journal_title：Acta neuropathologica
pub_type： 杂志文章,评审
doi：10.1007/s00401-013-1125-6
更新日期：2013-06-01 00:00:00
abstract：:A system is presented for the classification of chronic herniations of the cerebellar tonsils in the absence of space-occupying intracranial lesions, based on a survey of the literature and 13 own cases. The Arnold-Chiari malformation in adults typically involves herniation of the cerebellar tonsils instead of herniat...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688677
更新日期：1976-03-30 00:00:00
abstract：:Unusual inclusions with some of the features of "reducing bodies" were encountered in the skeletal muscle biopsy of a 2.5-year-old boy with childhood-onset acid maltase deficiency. The biopsy revealed a vacuolar myopathy with lysosomal storage of glycogen and eosinophilic refractile inclusions in myofibers, which appe...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00304641
更新日期：1992-01-01 00:00:00
abstract：:The gastrocnemius muscles of 3 groups of 10 rats, sacrified 5, 7, and 12 days respectively, following tenotomy, were submitted to different types of fixation, fixative and embedding. The occurrence of target fibres is shown not to be an artefact due to the histological procedures. Further examination demonstrates that...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690981
更新日期：1978-05-24 00:00:00
abstract：:We examined whether the Golgi apparatus (GA) is fragmented in nigral neurons in 18 cases with Parkinson's disease (PD) and in 8 control cases. The nigral neurons in cases with PD showed various degrees of Lewy pathology with alpha-synuclein immunohistochemistry, and we divided the neurons into three subtypes according...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-006-0114-4
更新日期：2006-09-01 00:00:00
abstract：:We examined the effect of lactic acid on cultured human glioma cell lines expressing glial fibrillary acidic protein (GFAP), vimentin and neuron-specific enolase (NSE). The growth of the cells was inhibited by the lactic acid in a dose-dependent manner. At 56 mM of lactic acid, the surviving cells of the KNS-42-c2 cel...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00296110
更新日期：1990-01-01 00:00:00
abstract：:Old age is associated with a deficient recovery from stroke, but the cellular mechanisms underlying such phenomena are poorly understood. To address this issue, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. Aged rats sh...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-006-0164-7
更新日期：2007-03-01 00:00:00
abstract：:The blood-brain barrier (BBB) was studied in rats with electrolyte-induced demyelination (EID), an experimental model for central pontine myelinolysis. Intravenously injected peroxidase was extravasated at 3 h post hypertonic saline injection (PHS) into regions frequently involved in EID. Increased pinocytotic activit...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00310371
更新日期：1994-01-01 00:00:00
abstract：:Following maternal chicken pox in the 14th week of pregnancy, a male infant was born with low birth weight, muscle wasting and limb contractures, hypotonia and areflexia. A rising titre of varicella-zoster-specific IgM (by enzyme-linked immunoabsorbent assay) confirmed congenital infection, and electromyogram showed w...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687781
更新日期：1988-01-01 00:00:00
abstract：:Prions cause scrapie and Creutzfeldt-Jakob disease (CJD); these infectious pathogens are composed largely, if not entirely, of protein molecules. No prion-specific polynucleotide has been identified. Purified preparations of scrapie prions contain high titers (greater than or equal to 10(9.5) ID50/ml), one protein (Pr...
journal_title：Acta neuropathologica
pub_type： 杂志文章,评审
doi：10.1007/BF00687261
更新日期：1987-01-01 00:00:00
abstract：:Oxidative stress has been implicated in the pathogenesis of a number of diseases including Alzheimer's disease (AD). The oxidative stress hypothesis of AD pathogenesis, in part, is based on beta-amyloid peptide (Abeta)-induced oxidative stress in both in vitro and in vivo studies. Oxidative modification of the protein...
journal_title：Acta neuropathologica
pub_type： 杂志文章,评审
doi：10.1007/s00401-009-0517-0
更新日期：2009-07-01 00:00:00
abstract：:Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the gradual appearance of α-synuclein (α-syn)-containing neuronal protein aggregates. Although the exact mechanism of...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-019-02099-5
更新日期：2020-02-01 00:00:00
abstract：:There is evidence that physical activity is associated with decreased brain injury resulting from transient middle cerebral artery (MCA) occlusion. We investigated whether exercise could reduce stroke-induced brain inflammatory injury and its associated mediators. Sprague Dawley rats (3 months old) were subjected to 3...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-004-0943-y
更新日期：2005-03-01 00:00:00
abstract：:The pattern of recovery of myelinated axons in the posterior tibial nerve after crushing was studied in rats chronically intoxicated with 2,5-hexanedione. It was given for 2 weeks before crushing (200 mg/kg i.p. 5 times a week) or additionally for two further weeks after the nerve crush. Two animals were examined from...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00703206
更新日期：1983-01-01 00:00:00
abstract：:Vascular smooth muscle cells are involved in deposition of amyloid in brain blood vessels. Accumulation of amyloid-beta peptide (Abeta) in cultured brain vascular smooth muscle cells that overexpress human amyloid-beta precursor protein (APP) Swedish, is strongly enhanced by exposure to iron ions. We studied cellular ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-009-0497-0
更新日期：2009-05-01 00:00:00
abstract：:To identify antigenic differences between gliomas and normal brain, we have immunohistochemically studied the expression of lymphocyte adhesion molecules (ICAM-1, ICAM-2, ICAM-3, VCAM-1, E-selectin and CD58), epidermal growth factor receptor (EGFR) and extracellular matrix proteins (collagen IV, fibronectin, laminin, ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050696
更新日期：1997-09-01 00:00:00
abstract：:It was earlier shown that bicuculline-induced status epilepticus gives rise to profound acute changes in the rat cerebral cortex, i.e. edema and neuronal alterations. In the present study, we explored to what extent interruption of the seizure activity reverses the changes observed. To that end, status epilepticus of ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00684924
更新日期：1983-01-01 00:00:00
abstract：:Primary extradural ependymomas are rare neoplasms usually of the myxopapillary type. Reports on malignant primary extradural ependymal tumors are exceptionally rare. We here report on a 3-year-old boy with Schinzel-Giedion syndrome (SGS), who presented with lumbar spina bifida occulta and a progressive extraspinal les...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-006-0179-0
更新日期：2007-03-01 00:00:00
abstract：:The caudate nucleus and putamen belong to the selectively vulnerable brain regions which incur neuronal damage in clinical and experimental settings of both hypoglycemia and ischemia. We have previously documented the density and distribution of the hypoglycemic damage in rat caudoputamen, but the evolution of the inj...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688122
更新日期：1985-01-01 00:00:00
abstract：:An extensive laminar spongiosis was found in the outer part of the dentate gyrus in an 84-year-old patient. An old cavitary infarct in the parahippocampal gyrus disconnected the dentate gyrus from the entorhinal area. This finding prompted us to seek laminar spongiosis in Alzheimer's disease, where the neuronal loss i...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050818
更新日期：1998-04-01 00:00:00
abstract：:In the nerve tissue with proliferating macroglia cells were observed a lowered oxygen consumption, an increased aerobic glycolysis and alanine formation and a higher alanine aminotransferase and glutamate dehydrogenase activity than in the control tissue in the homogenates and in the cell sap fraction. The substrate s...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00684665
更新日期：1976-03-15 00:00:00
abstract：:An unusual tumor of the pituitary gland is reported. The most characteristic finding of the present tumor was the presence of numerous "colloid" and mucoid secretions. The cells were stellate in shape and there were intra- or intercellular lumina which were lined by many microvilli and occasional cilia. There were als...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687617
更新日期：1984-01-01 00:00:00
abstract：:A histochemical study is reported of regional differences of the lipid storage in a case of Niemann-Pick disease (NPD) type C. Besides tissues known to be affected (reticulo-endothelium, hepatocytes, nervous system), storage was demonstrated in adrenal cortical spongiocytes, sweat glands, renal glomerular and tubular ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688393
更新日期：1975-12-19 00:00:00
abstract：:The activities of three enzymes of the hexose monophosphate pathway (HMP) were measured in frozen samples of rat cerebral cortex and ethylnitrosourea-induced tumors of the rat nervous system. Results show that in most tumors, adequate amounts of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogena...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690440
更新日期：1978-03-15 00:00:00
abstract：:Motor neuron disease (MND) may be complicated by frontotemporal dementia and/or an extrapyramidal movement disorder. Several studies have identified the pathological substrate for dementia in MND as being ubiquitin-immunoreactive inclusions and dystrophic neurites in the extramotor neocortex and hippocampus. Although ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-003-0814-y
更新日期：2004-04-01 00:00:00
abstract：:Apoptosis of neurons and glial cells has been shown to occur in the brain of patients with the acquired immune deficiency syndrome (AIDS) and was postulated as contributing to brain atrophy and white matter damage in these patients. Since apoptotic events may be induced by the Fas-Fas ligand (FasL) system, we analyzed...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010051094
更新日期：1999-10-01 00:00:00
abstract：:Keratan sulphate proteoglycan (KSPG) is a developmentally regulated barrier molecule, directing axonal growth during central nervous system (CNS) formation. The possible re-expression and functional significance of KSPG in preventing axon regeneration following spinal cord injury (SCI) is poorly understood. In the pre...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-002-0589-6
更新日期：2002-12-01 00:00:00
