CNS, and Schwann cells are the primary cause of this difference. Another key aspect is the change in permeability of the blood-tissue barrier in the two systems. In PNS, the permeability increases throughout the distal stump, but the barrier disruption in CNS is limited to just the site of injury. Clearance in PNS The response of Schwann cells to axonal injury is rapid. The time period of response is estimated to be prior to the onset of axonal degeneration. Neuregulins are believed to be responsible for the rapid activation. They activate ErbB2 receptors in the Schwann cell microvilli, which results in the activation of the mitogen-activated protein kinase (MAPK). Although MAPK activity is observed, the injury sensing mechanism of Schwann cells is yet to be fully understood. The 'sensing' is followed by decreased synthesis of myelin lipids and eventually stops within 48 hrs. The myelin sheaths separate from the axons at the Schmidt-Lanterman incisures first and then rapidly deteriorate and shorten to form bead-like structures. Schwann cells continue to clear up the myelin debris by degrading their own myelin, phagocytose extracellular myelin and attract macrophages to myelin debris for further phagocytosis. However, the macrophages are not attracted to the region for the first few days; hence the Schwann cells take the major role in myelin cleaning until then. Schwann cells have been observed to recruit macrophages by release of cytokines and chemokines after sensing of axonal injury. The recruitment of macrophages helps improve the clearing rate of myelin debris. The resident macrophages present in the nerves release further chemokines and cytokines to attract further macrophages. The degenerating nerve also produce macrophage chemotactic molecules. Another source of macrophage recruitment factors is serum. Delayed macrophage recruitment was observed in B-cell deficient mice lacking serum antibodies. These signaling molecules together cause an influx of macrophages, which peaks during the third week after injury. While Schwann cells mediate the initial stage of myelin debris clean up, macrophages come in to finish the job. Macrophages are facilitated by opsonins, which label debris for removal. The 3 major groups found in serum include complement, pentraxins, and antibodies. However, only complement has shown to help in myelin debris phagocytosis. Murinson et al. (2005) observed that non-myelinated or myelinated Schwann cells in contact with an injured axon enter cell cycle thus leading to proliferation. Observed time duration for Schwann cell divisions were approximately 3 days after injury. Possible