Journal of Neuropathology & Experimental Neurology:
In This Issue
Mitochondria in Peripheral Nerves Are Not Peripheral
This review by the Vitals addresses the histomorphology and mitochondrial DNA and dynamics related to the pathology of peripheral nerve diseases. This is an interesting topic that has been approached in a stimulating manner.
see page 1036
Defining the Many Roles of Dystroglycan in Brain Development
Type II (cobblestone) lissencephaly results from a defect in glycosylation, predominately of dystroglycan, that leads to an overmigration of cells beyond the pial-glial boundary. Myshrall et al show that dystroglycan is required in radial glial end feet to maintain the pial basement membrane, radial glial structure and localization, and dendrite orientation.
see page 1047
Decreased mRNA Expression of PGC-1α and PGC-1α–Regulated Factors in the SOD1G93A ALS Mouse Model and in Human Sporadic ALS
Peroxisome proliferator–activated receptor γ, coactivator 1 α (PGC-1α) plays a central role in the regulation of mitochondrial metabolism and biogenesis via activation of transcription factors. Thau et al provide evidence for a role of PGC-1α in mitochondrial dysfunction in both the SOD1G93A ALS mouse model and in human sporadic ALS, particularly in skeletal muscle.
see page 1064
Digital Pathology and Image Analysis for Quantitative Assessment of Alzheimer Disease Neuropathologic Changes
Using digitized images and pattern recognition software, Neltner et al designed algorithms for quantitation of amyloid and tau pathologies on immunostained sections of human brain. Their method had excellent interrater reliability and has the potential to make large-scale quantitative studies more feasible.
see page 1075
How Do You Connect Hypoxia, Epigenetics, and Brain Tumors?
Brain tumor stemlike cells (BTSCs) exist as a minor population in most malignant brain tumors. Kahlert et al show that the BTSCs are resistant to hypoxia and that this resistance is potentially mediated through epigenetic mechanisms, thereby offering a potential modality for treatment.
see page 1086
Brain and Lymphocytes Affected by Gene Dosage of DYRK1A Associated With Actin in Down Syndrome
The human DYRK1A gene on chromosome 21 encodes a proline-directed serine/threonine kinase and is triplicated in Down syndrome (DS). Dowjat et al investigated the effect of abnormal levels of this kinase on the cytoskeleton in brain and lymphocytes of DS subjects. The DYRK1A protein was increased and associated with actin; alterations of DYRK1A-actin assemblies were detected in newborn and infant DS groups. These results link DYRK1A overexpression with abnormal brain development and other systemic manifestations of DS.
see page 1100
The Pathology of MRI Hyperintensity in Normal White Matter
Murray et al analyzed the relationship between postmortem fluid-attenuated inversion recovery (FLAIR) intensity and neuropathologic markers of white matter lesions that correspond to white matter hyperintensity in cognitively normal aging brains. Their data indicate that age-related loss of myelin and a decrease in small vessel density contribute to the vacuolation of white matter manifested in elevated white matter FLAIR intensity in the cognitively normal elderly.
see page 1113
BDNF, Fibroblasts, and Murine Brain Hemorrhage
Chen et al tested the efficacy of fibroblast and brain-derived neurotrophic factor (BDNF) treatment in a mouse model of intracerebral hemorrhage (ICH). Their results indicate that fibroblast transplantation, together with recombinant BDNF treatment, after ICH promotes neurogenesis and early functional recovery. This study suggests a potential approach for combining gene and cell therapy for the treatment of ICH.
see page 1123
Ibuprofen to the Rescue in Neonatal Hypoxic-Ischemic Brain Damage
Neonatal hypoxic-ischemic injury remains as a significant contributing factor to the morbidity and mortality of brain injury related to prematurity; there are few treatment options.
Wixey et al demonstrate that, in an animal model, ibuprofen may help mitigate the neuroinflammatory contribution to the brain injury associated with hypoxic-ischemic injury.
see page 1137