title: Proliferating immature Schwann cells contribute to nerve regeneration after ischemic peripheral nerve injury.
abstract: Schwann cells exhibit a high degree of plasticity in adult peripheral nerves after mechanical injury; they have, therefore, been implicated in promoting nerve regeneration. However, Schwann cell behavior after ischemic injury has not yet been elucidated. To determine how Schwann cell plasticity may contribute to recovery from ischemic neuropathy, we used a rat model in which ischemia was induced in the tibial nerve by a 5-hour occlusion of the supplying arteries. Proliferation of immature Schwann cells that emerged in the injured nerve was evaluated by double immunostaining for the p75 neurotrophin receptor and proliferating cell nuclear antigen. The number of proliferating cell nuclear antigen/p75 neurotrophin receptor double-positive cells increased significantly in 1 to 2 weeks after ischemia and subsequently decreased by 4 weeks. During this time, the postmitotic Schwann cells differentiated into mature cells, as demonstrated with bromodeoxyuridine incorporation, which facilitated axon guidance and subsequent axon remyelination. These results suggest the emergence and proliferation of immature Schwann cells that contribute to nerve regeneration after ischemic injury. The manipulation of this population of proliferating immature Schwann cells may be a useful strategy for treating ischemic peripheral neuropathy.
authors.affiliation: Department of Neurology and Neurological Science, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Ishibashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomimitsu
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
mesh_terms: D000818:Animals; D000963:Antimetabolites; D001369:Axons / Q000502:physiology; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation; D007839:Functional Laterality / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply / Q000294:innervation; D007150:Immunohistochemistry; D007511:Ischemia; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000473:pathology*; D051381:Rats; D020127:Recovery of Function / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000502:physiology*; D013979:Tibial Nerve / Q000473:pathology; D016707:Tissue Fixation
chemical_list: D000963:Antimetabolites; D009418:S100 Proteins; D001973:Bromodeoxyuridine