2007), indicating that JAM-C plays an important role in myelination and/or myelin stabilization. Biopsies obtained from patients with chronic inflammatory demyelinating polyneuropathy displayed reduced numbers of JAM-C immunoreactive paranodal regions, in accord with a demyelinated state of nerve. In the peripheral nervous system (PNS), myelinating Schwann cells wrap around axons,

organizing the axonal membrane into distinct domains (Salzer 2008; Susuki and Rasband 2008). Efficient propagation at the nodes of Ranvier is facilitated by tight interactions between the axon and glial cells at the paranodal regions and between adjacent membrane layers of individual glial cells Inhibitors,research,lifescience,medical (autotypic junctions) (Poliak and Peles 2003). JAM-C expression in peripheral nerve lies selectively along Inhibitors,research,lifescience,medical the whole length of the paranodal terminal loops (Scheiermann et al. 2007), similar to other components of autotypic junctions, such as claudin-19 (Miyamoto et al. 2005). JAM-C is also enriched in Schmidt–Lantermann

incisures, that is, Inhibitors,research,lifescience,medical conical tube-like structures that spiral through regions of compact lamellae. Since these noncompacted regions connect the Schwann cell body and the periaxonal cytoplasm, they are thought to act as highways for transport of metabolic substances (Berger and Gupta 2006). Following crush injury, nerve fibers distal to the lesion degenerate in a process known as Wallerian degeneration. Schwann cells dedifferentiate, reversing molecular expression from a mature myelinating state to an immature one (Jessen and Mirsky 1999), and express surface molecules resulting in a permissive environment for axonal regeneration and remyelination (Abercrombie and Johnson 1946; Fawcett and Keynes 1990; Muller and Stoll 1998). As the Schwann cells Inhibitors,research,lifescience,medical begin to form myelin lamellae on the axon, the molecular phenotype switches back to its Inhibitors,research,lifescience,medical mature type. Schwann cells thus play an important role following nerve injury, not only in supporting axon regeneration but also in remyelinating

regenerated axons. Since JAM-C is expressed by myelinating Schwann found cells, and the JAM-C knockout has disrupted myelin (Scheiermann et al. 2007), we hypothesize that JAM-C may play an important role in the process of remyelination after nerve injury. To elucidate this hypothesis, we have examined the spatial and temporal patterns of JAM-C localization during peripheral nerve regeneration and remyelination of the rat sciatic nerve. To our knowledge, this is the first study to examine the effect of nerve learn more injury on JAM-C localization. Methods and Materials Animals and surgical procedures Adult male Wistar rats (225–250 g) were deeply anesthetized in a fume box using 5% isofluorane (Meril, Essex, UK), in addition to a mixture of oxygen and nitrous oxide (1:1 ratio), at a flow rate of 750–1000 mL/min. Subsequent anesthesia throughout the procedure was maintained using 2–2.