A single intracerebral microinjection of platelet-derived growth factor (PDGF) accelerates the rate of remyelination in vivo.
We had demonstrated that platelet-derived growth factor (PDGF) enhanced the reconstruction of myelin-like membranes after their disruption by lysophosphatidylcholine (LPC) in vitro. To investigate its role in vivo, a demyelinating lesion of the corpus callosum was induced in adult Wistar rats by a stereotaxic microinjection of 1 microl LPC, then 63 pairs of rats received either 1 microg PDGF, or its vehicle buffer which were injected above LPC. The effects of PDGF were significant after 2 weeks: the number of oligodendrocytes (OL) expressing 2',3'-cyclic nucleotide 3'-phosphodiesterase in the lesion increased by 49%, mature OL labelled by in situ hybridization for myelin basic protein-mRNA increased by 27% (P<10(-2)), and the total volume of demyelination decreased by 60% compared to controls. The proliferation of cells of the OL lineage was also enhanced up to 67% by PDGF compared to LPC controls (P<2.5 x 10(-2)). Ultrastructural studies confirmed this dramatic improvement, and the ratio of remyelinated to demyelinated axons, determined at the maximal demyelination site, in the centre of the lesion, increased by 10-fold (P<2.5 x 10(-3)) in animals treated with PDGF. Remyelination was complete after 3 months for both treatments. Neither exacerbation of gliosis nor glial tumoural transformation were observed. Mechanisms through which PDGF improves remyelination could involve proliferation of OL progenitors, and/or of already differentiated surviving OLs, and a chemotactic effect, which had been identified in vitro.
Allamargot
C
C
Cell Biology Department, University Hospital, 4 rue Larrey, F49033 Angers Cedex 01, France.
Pouplard-Barthelaix
A
A
Fressinaud
C
C
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003337:Corpus Callosum / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D007150:Immunohistochemistry; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D004676:Myelin Basic Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
D008244:Lysophosphatidylcholines; D004676:Myelin Basic Protein; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger