Journal of neuropathology and experimental neurology
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J. Neuropathol. Exp. Neurol. · Aug 2013
Diffuse traumatic axonal injury in the optic nerve does not elicit retinal ganglion cell loss.
Much of the morbidity after traumatic brain injury (TBI) is associated with traumatic axonal injury (TAI). Although most TAI studies focus on corpus callosum white matter, the visual system has received increased interest. To assess visual system TAI, we developed a mouse model of optic nerve TAI. ⋯ Persistent RGC survival was also consistent with the finding of reorganization in the proximal axonal segments after TAI, wherein microglia/macrophages remained inactive. In contrast, activated microglia/macrophages closely enveloped the distal disconnected, degenerating axonal segments at 7 to 28 days after injury, thereby confirming that this model consistently evoked TAI followed by disconnection. Collectively, these data provide novel insight into the evolving pathobiology associated with TAI that will form a foundation for future studies exploring TAI therapy and its downstream consequences.
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J. Neuropathol. Exp. Neurol. · Sep 2012
Gadolinium- and 5-aminolevulinic acid-induced protoporphyrin IX levels in human gliomas: an ex vivo quantitative study to correlate protoporphyrin IX levels and blood-brain barrier breakdown.
In recent years, 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence guidance has been used as a surgical adjunct to improve the extent of resection of gliomas. Exogenous administration of ALA before surgery leads to the accumulation of red fluorescent PpIX in tumor tissue that the surgeon can visualize and thereby discriminate between normal and tumor tissue. ⋯ We found positive correlations between PpIX concentration and Gd concentration (r = 0.58, p < 0.0001) and between PpIX concentration and microvascular density (r = 0.55, p < 0.0001), suggesting a significant, yet limited, association between blood-brain barrier breakdown and ALA-induced PpIX fluorescence. To our knowledge, this is the first time that Gd measurements by inductively coupled plasma mass spectrometry have been used in human gliomas.
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J. Neuropathol. Exp. Neurol. · Jul 2012
Review Case ReportsUpdate on PML and PML-IRIS occurring in multiple sclerosis patients treated with natalizumab.
The use of natalizumab to treat multiple sclerosis (MS) has been associated with the development of progressive multifocal leukoencephalopathy (PML), with 242 PML cases reported as of May 3, 2012. Fortunately, rapid withdrawal of the drug and administration of plasma exchange has allowed survival in many of these patients, but a new problem, immune reconstitution inflammatory syndrome (IRIS), has emerged after drug withdrawal. This report provides an update on PML in natalizumab-treated patients and reviews what is currently known about PML-IRIS in this setting; autopsy findings from a well-studied patient are illustrated. ⋯ Immune reconstitution inflammatory syndrome was diagnosed, comfort care was instituted, but demise did not occur until 9 months later. Autopsy showed ongoing severe PML-IRIS, with massive cavitary brain lesions containing abundant perivascular and parenchymal CD8-positive T-cell infiltrates. Bone marrow and spleen, but not brain, contained monoclonal T-cell populations by polymerase chain reaction-based gene rearrangement studies, indicating overstimulation of peripheral T cells; T-cell lymphoma was not identified by morphological or immunohistochemical criteria.
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J. Neuropathol. Exp. Neurol. · Apr 2012
Comparative StudyModerate traumatic brain injury triggers rapid necrotic death of immature neurons in the hippocampus.
Traumatic brain injury (TBI) causes cell death predominantly in the cerebral cortex, but there is additional secondary cell death in the hippocampus. We previously found that most of the dying cells in the mouse hippocampus are newborn immature granular neurons in a mouse model of lateral controlled cortical impact (CCI) injury with a moderate level of impact. It is not known how long this selective cell death in the hippocampal dentate gyrus lasts, and how it is induced. ⋯ Most of the dying immature granular neurons did not exhibit morphologic characteristics of apoptosis, and only a small subpopulation of the dying cells was positive for apoptotic markers. In contrast, most of the dying cells coexpressed the receptor-interacting protein 1, a marker of necrosis, suggesting that immature neurons mainly died of necrosis. These results indicate that moderate TBI mainly triggers rapid necrotic death of immature neurons in the hippocampus in a mouse CCI model.