Journal of Neuropathology & Experimental Neurology:
In This Issue
Receptors Take Their Toll
Toll-like receptors (TLRs) are known for their role in innate immunity by serving as surveillance receptors in response to microorganisms. Stenzel-Poore et al review the more recent appreciation of the role TLRs play in contributing to ischemic damage initially, while subsequently conferring neuroprotection.
see page 378
A New Mouse Model for Neonatal Intracerebral Hemorrhage
In preterm neonates, intraventricular and parenchymal hemorrhages are important clinical problems that have contributions from both the environment and the genome. Leroux et al demonstrate the utility of plasminogen activator inhibitor-1 knockout mice as a genetic model of this disorder; it should facilitate further investigations of pathogenesis and therapeutic approaches.
see page 387
Feline complex partial seizures with orofacial involvement (FEPSO) and some cases of human limbic encephalitis (LE) are associated with anti-voltage-gated potassium channel complex antibodies (VGKC-Abs). Klang et al examined the brains of cats with FEPSO and compared the findings to those in human VGKC-Ab-associated LE. Their observations provide further evidence that FEPSO is a feline form of the human disease with similar immunopathologic mechanisms.
see page 403
Neuroprotective Potential of Adenosine A2A and Cannabinoid CB1 Receptor Antagonists in an Animal Model of Parkinson Disease (PD)
Both an adenosine A2A receptor antagonist (MSX-3) and a cannabinoid CB1 receptor antagonist (rimonabant) increased dopaminergic neuron survival in substantia nigra in the 6-OHDA PD model. These protective effects were not additive, however, and in fact diminished when the compounds were combined.
see page 414
Sugars Important for Brain and Muscle Development
LARGE encodes for one of 14 glycosyltransferases implicated in congenital muscular dystrophies with varying brain and eye phenotypes. It transfers the final moieties on to glycoproteins including α-dystroglycan. Four new patients with mutations in LARGE expand the phenotype of this disorder and provide the first neuropathologic description.
see page 425
How Oligodendrocyte Nuclei Grow in Progressive Multifocal Leukoencephalopathy
Shishido-Hara et al analyzed the evolution of intranuclear viral inclusions and the relationships of promyelocytic leukemia nuclear bodies (PML-NBs) to nuclear size and cell cycle transitions in progressive multifocal leukoencephalopathy. Their data suggest that JC virus produces progeny virions in enlarging oligodendrocyte nuclei in association with growing PML-NBs and with cell cycle transition through S to G2.
see page 442
Anti-CD40 Treatment of Experimental Autoimmune Neuritis (EAN)
Brunn et al show that elimination of the costimulatory molecule CD40 by knockout or antibody treatment can ameliorate clinical and pathological parameters of EAN in mice. CD40 is involved in CD4-positive T cell activation and homing to the nerves via effects on the NF-κB signaling pathway and generation of regulatory T cells. The results suggest that CD40 may be a useful therapeutic target in human neuritides.
see page 454
A Novel GRN Mutation in Frontotemporal Lobar Degeneration (FTLD)
Clinical, genetic, and neuropathologic findings in 6 patients with a novel progranulin gene (GRN) mutation are reported. Although all patients had TDP-43 pathology, 4 showed a type A pattern, 2 showed an overlap between types A and B, and in 1 the lesions were subtle, indicating the need to evaluate TDP-43 lesions carefully in cases of possible FTLD. The study underscores the utility of neuropathologic evaluation in confirming the pathogenic nature of newly discovered genetic variations.
see page 467
Papillary Glioneuronal Tumor (PGNT) with Anaplastic Features
Follow-up data are reported on a young woman with a PGNT that metastasized systemically and caused her death despite aggressive surgical intervention, radiation and chemotherapy. This case illustrates the need for a tiered WHO grading scheme for PGNTs.
see page 474
© 2014 by American Association of Neuropathologists, Inc.