Cellular reactions at the lesion site after crushing of the rat optic nerve.
Rat optic nerves were subjected to crush injury to study the local tissue reactions leading to wound healing and tissue repair. We used antibodies against glial fibrillary acidic protein (GFAP), vimentin, the S1OO protein (S1OOP), lysozyme, and ED1 as markers for astroglial cells and microglia/macrophages at the light and electron microscopic level during the 3 weeks following the crush. The crush injury produced a vast area of tissue damage including the disruption of the blood-brain barrier (BBB). In the first days after crushing, astrocytes were absent from the lesion site. S1OOP-positive astrocytes reappeared in the lesion center as early as 6 days after crushing. These astrocytes reestablished former topological structures such as perivascular and subpial glia limitans. At the edges of the lesion site reactive astrocytes enclosed and embedded axonal and myelin debris. Preceding the astroglial repopulation, a massive infiltration of microglia/macrophages (phagocytes) into the lesion center took place. ED1-positive/lysozyme- positive cells of round shape were seen in the lesion center at 2 days after crushing, and their number peaked around 1 week after crushing. They efficiently cleared the debris from the lesion site and mostly disappeared after 3 weeks. With immuno-electron microscopy we found the ED1 antigen related to the membranes of phagosomes. The microglia/macrophages observed in the nerve segments distal of the lesion (Wallerian degeneration site) were different from those in the lesion center: 1) they appeared later, about 6 days after crushing; 2) they were ED1 positive, but lysozyme negative and showed a branched morphology; and 3) they persisted in the distal nerve segment but showed little phagocytosis. We suggest that these cells are mostly activated microglia.
Frank
M
M
Universitat Tubingen, Institut fur Pathologie, Germany.
Wolburg
H
H
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D002452:Cell Count; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008854:Microscopy, Electron; D009409:Nerve Crush; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology*; D020221:Optic Nerve Injuries; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D015415:Biomarkers