Acta neuropathologica
-
Acta neuropathologica · Nov 2007
Increased caveolin-1 expression precedes decreased expression of occludin and claudin-5 during blood-brain barrier breakdown.
The significance of caveolin-1, a major constituent of caveolae, and the tight junction proteins occludin and claudin-5 in early blood-brain barrier (BBB) breakdown was assessed by sequential demonstration of the expression of these proteins over a period of 12 h to 6 days post-lesion in the rat cortical cold injury model. Pial and intracerebral vessels of control rats showed punctuate endothelial immunoreactivity for caveolin-1 and caveolin-2, while claudin-5 and occludin were localized as longitudinal strands in endothelium. During the early phase of BBB breakdown following injury at 12 h and on day 2, western blot analyses detected a significant increase in caveolin-1 expression at the lesion site while immunohistochemistry showed that the caveolin-1 increase was localized to the endothelium of lesion vessels. ⋯ Dual labeling for fibronectin, a marker of BBB breakdown, and caveolin-1 or the tight junction proteins demonstrated that only lesion vessels with BBB breakdown showed a marked increase of caveolin-1, loss of occludin and reduced localization of claudin-5. The issue whether these alterations precede or follow BBB breakdown is uncertain; however, increased expression of caveolin-1 preceded the decreased expression of occludin and claudin-5. Thus caveolae and caveolin-1 have an important role in early BBB breakdown and could be potential therapeutic targets in the control of early brain edema.
-
Acta neuropathologica · Jun 2006
Canine cognitive deficit correlates with diffuse plaque maturation and S100beta (-) astrocytosis but not with insulin cerebrospinal fluid level.
Like humans, canines develop with aging beta-amyloid (Abeta) plaques and a progressive cognitive deficit on tasks similar to those used in diagnosis and follow-up of Alzheimer's disease. Owing to that, dogs are quite unique to investigate the early events taking place in the diffuse Abeta plaque maturation and its relationship with cognitive deficit. ⋯ Abeta plaques were measured and counted in prefrontal cortex of 16 pet dogs of different breeds, weight and sex, classified as control and with a light or severe cognitive deficit. A correlation between canine graded cognitive deficit, diffuse plaque maturation, and S100beta (-) astrocytosis, but not with cerebrospinal fluid insulin level, was found that may reflect the very early events of Abeta deposition in Alzheimer's disease.
-
Acta neuropathologica · Apr 2006
Case ReportsGlioblastoma multiforme with small cell neuronal-like component: association with human neurotropic JC virus.
The human polyomavirus JCV, the etiological agent of progressive multifocal leukoencephalopathy, has been associated with primitive neuroectodermal tumors and various glial-derived tumors, including glioblastoma multiforme (GBM). Here we describe the unique clinical case of a 54-year-old man who presented with headaches, hemiparesis and drowsiness. T1 and T2 magnetic resonance images revealed a large solid tumor with a cystic component located in the right temporal lobe, with extension into the parietal lobe. ⋯ No evidence for capsid protein was observed, excluding productive viral infection. Sequencing demonstrated the presence of the JCV Mad-1 strain with distinct point mutations in the CR of isolates from both, GBM and small cell architectural areas. The presence of JCV DNA sequences and expression of viral proteins further reinforces the role of the widely spread human neurotropic virus in early transformation and in the development of brain tumors.
-
Acta neuropathologica · Dec 2005
Comparative StudyHypoxic-ischemic brain injury in infants with congenital heart disease dying after cardiac surgery.
Cardiac surgery for congenital heart disease is performed increasingly earlier in infancy, including in the neonatal period. With increased survival of infants, there is growing concern about the long-term neurological sequelae of hypoxic-ischemic injury due to congenital heart disease itself prior to surgery, corrective surgery with the use of low-flow cardiopulmonary bypass (CPB) and/or deep hypothermic circulatory arrest (DHCA), and/or unstable hemodynamic factors postoperatively. In analyzing the neuropathology of 38 infants dying after cardiac surgery, we tested a set of questions related to the severity and patterns of brain injury, CPB, DHCA, and age of the infants at the time of surgery. ⋯ There was no significant association between the age at the time of surgery (neonatal versus postneonatal) and the severity of overall brain injury. The patterns of brain injury were not age-related in the limited time-frame analyzed, except that infants who developed acute PVL after both closed and DHCA/CPB surgery (14/38 infants, 34%) were significantly younger at death (median age 13.0 days) compared to unaffected infants (median age at death 42.5 days) (P=0.031). This observation suggests that neonatal (<30 postnatal days), but not postneonatal (>30 postnatal days), brains are at risk for acute PVL, and likely reflects the vulnerability of immature (pre-myelinating) white matter to hypoxia-ischemia.
-
Acta neuropathologica · Nov 2005
Case ReportsPrion disease with a 144 base pair insertion: unusual cerebellar prion protein immunoreactivity.
Sporadic, acquired, and genetic human prion diseases are characterized neuropathologically by distinct deposition patterns of the abnormal, disease-associated form of the prion protein (PrP(sc)). In addition to mutations in the prion protein gene (PRNP), PrP(sc) immunostaining patterns correlate with molecular phenotypes of prion diseases defined by the PRNP polymorphism at codon 129 and with protease-resistant PrP classified by Western blotting. Some point or insertional PRNP mutations share similar clinical and neuropathological phenotypes, whereas others show great variability even within the same family. ⋯ Our case reinforces the importance of molecular genetic diagnosis, especially in those patients who lack a family history of prion disease and show unusual neuropathological changes. It also widens the phenotypic spectrum of prion diseases. The phenotypic variability within the same mutation suggests further, yet uncharacterized, genetic or epigenetic influence on phenotype in these diseases.