Blood-brain barrier permeability in astrocyte-free regions of the central nervous system remyelinated by Schwann cells.
The patency of the blood-brain barrier was examined during the development and repair of focal demyelinating lesions induced in the dorsal columns of rats by the intraspinal injection of ethidium bromide, with or without concomitant irradiation. Blood-brain barrier integrity was determined by the intravenous injection of horseradish peroxidase or by the immunofluorescent localization of endogenous albumin. Following repair, the central area of the lesions was remyelinated by Schwann cells and lacked astrocytes. In unirradiated lesions, demyelination was established at one week and the lesion was largely repaired by remyelination by 12 weeks. Horseradish peroxidase extravasation was absent at one day after injection, but was present at three days and throughout the period of repair. With one exception, all animals which exhibited regions of demyelination also exhibited horseradish peroxidase extravasation. No horseradish peroxidase was seen in lesions where all the demyelinated axons had been repaired by remyelination, and strong albumin immunofluorescence was also absent from such lesions. Albumin immunoreactivity was also absent from normal spinal cords, although it was prominent in normal sciatic nerves and dorsal roots. Irradiation of lesions resulted in a delay in the repair by remyelination, and repair of the blood-brain barrier was similarly delayed. Promotion of Schwann cell remyelination has been suggested as a potential therapy for central demyelinating disorders such as multiple sclerosis; however, central regions remyelinated by Schwann cells lack astrocytes, cells which have been implicated in the induction and maintenance of the blood-brain barrier. Since blood-brain barrier opening may be an early step in the production of new lesions, a defective barrier could allow such remyelinated regions to act as foci for further lesion development. We conclude, however, that the remyelination of central demyelinating lesions by Schwann cells is accompanied by recovery of properties of an intact blood-brain barrier, despite the lack of astrocytes. The present findings support the idea that promotion of remyelination by Schwann cells may form an effective therapy for central demyelinating diseases.
Felts
P A
PA
Department of Neurology, United Medical School, Guy's Hospital, London, U.K.
Smith
K J
KJ
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006651:Histocytochemistry; D006735:Horseradish Peroxidase; D008297:Male; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000502:physiology* / Q000648:ultrastructure; D012709:Serum Albumin
D005904:Glial Fibrillary Acidic Protein; D012709:Serum Albumin; D006735:Horseradish Peroxidase