Journal of Neuropathology & Experimental Neurology:
In This Issue
Faim2 the Rescue in Bacterial Meningitis?
Fas-apoptotic inhibitory molecule 2 (Faim2) is a neuron-specific membrane protein with neuroprotective effects. Tauber et al show that hippocampal Faim2 expression is altered in human bacterial meningitis and that Faim2 deficiency in a mouse bacterial meningitis model aggravates neurodegeneration in the acute phase but induces regeneration in the repair phase. Their findings suggest that there may be a time window for modulation of neuroplasticity by Faim2 in reducing hippocampal neuronal cell death and improving cognitive deficits after bacterial meningitis.
see page 2
Trauma Today, Inflammation Tomorrow
Although it is known that traumatic brain injury (TBI) results in chronic and progressive neurodegeneration, the mechanisms responsible for this neurodegeneration are not understood. Using a rodent model of TBI, Loane et al show that lesion volume expansion, neuronal loss, and microglial activation continue to increase for a year after TBI and identify several key biochemical changes associated with this pathology. These findings define a prolonged window during which TBI can potentially be treated and suggest that manipulating microglial function may limit neurologic damage during this period.
see page 14
Argyrophilic Grains Are Disease-Specific Features of Corticobasal Degeneration (CBD)
Tatsumi and colleagues unequivocally illustrate that CBD is marked by grains in the temporal lobe with characteristics identical to those seen in argyrophilic grain disease. These are not merely the consequence of aging but are rather constant alterations in this tauopathy.
see page 30
High-Resolution Imaging Provides a View of Murine Mucopolysaccharidosis (MPS) Model Pathology
Magnetic resonance imaging has evolved to resolve structures at the micrometer level along with algorithms permitting the evaluation of white matter tracts. Kumar and colleagues have used this to examine the structural changes in a mouse MPS model and correlate their data with histology.
see page 39
The VHL Gene in Sporadic and Von Hippel Lindau Syndrome (VHLS)–Associated CNS Capillary Hemangioblastomas (HGBs)
Muscarella et al investigated VHL mutations and expression in HGB from patients with apparently solitary CNS HGB and with VHLS. They found somatic VHL mutations in more than half of apparently non–VHLS-related cases and 7 new VHL alterations. Their results confirm the usefulness of VHL gene analysis at the germline level in patients with apparently solitary HGB. Moreover, the results support a key role for functional alterations of the VHL gene in sporadic neuraxial HGB.
see page 50
Interfering With Interferon (IFN) in HIV-1 Neuropathogenesis
Interferon signaling has been reported to have both protective and deleterious effects in HIV infection. He et al addressed this conundrum using mice deficient in type 1 IFN receptor (IFNRKO). Their investigations show that type 1 IFN signaling and responses limit HIV-1 infection and pathogenesis in murine brains, thus supporting a protective function.
see page 59
Neuropathologic Heterogeneity Does Not Impair Florbetapir–Positron Emission Tomography (PET) Postmortem Correlates
In vivo amyloid imaging shows promise in identifying patients with Alzheimer disease–related pathology, many of whom also have Lewy body disease (LBD) or other concurrent findings. Comparison of quantitative florbetapir F-18 PET imaging with postmortem histopathology shows that the PET signal is not affected by the presence or absence of LBD, severe cerebral amyloid angiopathy, argyrophilic grains, or TDP-43 inclusions.
see page 72
Gliopathies in Tauopathies
Ferrer et al compared the morphology and posttranslational modifications of tau deposits in neurons and glia in various human tauopathies using immunohistochemistry, immunofluorescence, and confocal microscopy. They found that the biochemical features of tau deposits in astrocytes largely paralleled changes in neuronal tau that are characteristic of a given disorder; oligodendroglial inclusions were less variable between diseases. Their findings suggest that disease-specific pathogenetic mechanisms have the potential to affect neuronal and glial cytoskeletal elements in a similar, but not always identical, manner. They also hypothesize that variations in morphology of altered astrocytes between diseases reflect selective vulnerability of various subpopulations of astrocytes.
see page 81
© 2014 by American Association of Neuropathologists, Inc.