Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 63, Issue 1, Pages 73-83Publisher
AMER ASSN NEUROPATHOLOGISTS INC
DOI: 10.1093/jnen/63.1.73
Keywords
astrocytes; blood brain barrier; cytokines; electron microscopy; immunohistochemistry; neuroprotection; neurotrophins
Categories
Funding
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS039092] Funding Source: NIH RePORTER
- NINDS NIH HHS [NS39092] Funding Source: Medline
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Microvascular (capillary) proliferation is a readily observed, but largely ignored phenomenon of the mesial temporal lobe epilepsy (MTLE) hippocampus. Here, we report that the proliferated capillaries in surgically resected MTLE hippocampi were strongly immunoreactive for erythropoietin receptor (EPO-r). Further, we found that these capillaries were most prominent in areas of the MTLE hippocampus with extensive neuronal loss and gliosis, i.e. the CA3, CA1, and dentate hilus. High-resolution immunogold electron microscopy revealed that the capillary EPO-r was localized to the luminal and abluminal plasma membrane of endothelial cells, to endosome-like structures of these cells, and to pericapillary astrocytic end-feet. Previous studies have shown that systemically administered EPO appears in the cerebrospinal fluid in experimental animals, and the present results are consistent with the idea that EPO enters the brain via receptor-mediated endocytosis. The enrichment of EPO-r shown here suggests a highly efficient uptake of plasma EPO into the MTLE hippocampus and a possible role for this cytokine in epileptogenesis. Moreover, the presence of EPO-r in the MTLE hippocampus may provide a new vehicle for highly efficient delivery of hitherto impermeable drugs into the epileptic brain.
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