Reconstruction of transected postcommissural fornix in adult rat by Schwann cell suspension grafts.
Schwann cell (SC) transplantation has emerged as a powerful tool to promote regeneration in the lesioned central nervous system (CNS). Most studies focused on the use of guidance channels to introduce the SCs into CNS neuropil; a technique that itself causes extensive damage to host tissue and is only applicable in superficial brain areas. The present study examines the efficacy of microinjected SC suspensions to promote structural reconstruction of the transected postcommissural fornix in the adult rat. Stereotactic, unilateral fornix transection was performed using a tungsten wire knife. Immediately after transection lesion cavities received either a Dulbecco's modified Eagle's medium injection or a pure SC suspension graft derived from a highly purified SC culture that was prepared from syngeneic rat (P1) sciatic nerves. After 4 days to 8 months, the implant characteristics as well as the structural reconstruction of the tract were analyzed using immunocytochemical methods and anterograde tracing techniques. Numerous SCs of the graft could be identified for up to 8 months. They rapidly dispersed from the injection site and migrated freely for considerable distances into the host tissue. The SCs exhibited a low proliferation activity that ceased within 2 weeks after transplantation. They did not prevent retrograde axonal degeneration of the fornix tract for a short distance (600 micron) but promoted structural reconstruction of the transected fornix tract. Regenerating fibers traversed the lesion site and extended along their former pathway up to the mammillary body, their proper target. Moreover, the applied transplantation technique allowed remyelination of the regenerating fibers by host oligodendrocytes. In conclusion, microtransplantation of SC suspensions represents a promising strategy for promoting structural reconstruction of lesioned CNS projections.
Stichel
C C
CC
Molecular Neurobiology Laboratory, Department of Neurology, University of Düsseldorf, Germany.
Lips
K
K
Wunderlich
G
G
Müller
H W
HW
D000818:Animals; D016380:Brain Tissue Transplantation; D002478:Cells, Cultured; D006624:Hippocampus / Q000502:physiology*; D007150:Immunohistochemistry; D009412:Nerve Fibers / Q000737:chemistry / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000502:physiology / Q000637:transplantation*