The Cnspns Transitional Zone

Dorsal and ventral spinal roots and cranial nerves III-XII are attached to the CNS by thin rootlets. At this attachment afferent axons shift from PNS to CNS features, and efferent axons shift from CNS to PNS characteristics. The rootlet segment containing both CNS and PNS tissue is the transitional zone (TZ). In the TZ, CNS tissue is separated from PNS tissue by the glia limitans and its basal lamina.

With respect to the structure of the TZ, there is a considerable variation between different nerves and between individual rootlets of a given nerve (Fig. 20A; see Fraher, 1992). The CNS-PNS borderline may be convex with projection of CNS tissue into the PNS, flat, or concave with projection of PNS tissue into the CNS. At the CNS-PNS transition of some nerves, PNS tissue forms isolated islands within the CNS. Similarly, isolated islands of CNS tissue may be located within the PNS part of a rootlet (Fig. 20A; see Fraher 1992). As a rule, CNS tissue extends into the rootlets, forming a central tissue projection (see Berthold and Carlstedt, 1977a; Berthold et al., 1984; Fraher, 1992).

On the CNS side of the glia limitans, the nerve fibers coursing between the CNS and the PNS are surrounded mainly by astrocytic processes emerging from perikarya in the glia limitans. Oligodendrocytes and a few microglial cells are also present. On the PNS side of the glia limitans, the nerve fibers are surrounded by endoneurial connective

Figure I 9 Hypothetical scheme illustrating the theory of myelin turnover discussed in Section II. Nodal-paranodal-juxtaparanodal region of a large CNS fiber with associated Marchi-negative (stippled) and Marchi-positive (black) myelinoid bodies. The latter are detached from the fiber, taken up by perinodal astrocytic processes (A = astrocyte) and transferred to microglial cells (M). The latter digest the engulfed myelinoid bodies and the breakdown products are reutilized by oligodendroglia (O). (With permission from Hildebrand et al., 1993.)

Figure I 9 Hypothetical scheme illustrating the theory of myelin turnover discussed in Section II. Nodal-paranodal-juxtaparanodal region of a large CNS fiber with associated Marchi-negative (stippled) and Marchi-positive (black) myelinoid bodies. The latter are detached from the fiber, taken up by perinodal astrocytic processes (A = astrocyte) and transferred to microglial cells (M). The latter digest the engulfed myelinoid bodies and the breakdown products are reutilized by oligodendroglia (O). (With permission from Hildebrand et al., 1993.)

Figure 20 (A) Principal types of anatomy at the TZ. Black indicates CNS tissue; white indicates PNS tissue. (With permission from Fraher, 1992.) (B) Transitional node of Ranvier (BN) in a S1 dorsal rootlet in an adult cat. The PNS part is located to the right (P) and the central part is located to the left (C). Note that the node gap contains both astrocytic processes and Schwann cell extensions. A perinodal astrocyte containing some gliosomes is located close to the node. (x7,700.) (With permission from Berthold and Carlstedt, 1977b.)

Figure 20 (A) Principal types of anatomy at the TZ. Black indicates CNS tissue; white indicates PNS tissue. (With permission from Fraher, 1992.) (B) Transitional node of Ranvier (BN) in a S1 dorsal rootlet in an adult cat. The PNS part is located to the right (P) and the central part is located to the left (C). Note that the node gap contains both astrocytic processes and Schwann cell extensions. A perinodal astrocyte containing some gliosomes is located close to the node. (x7,700.) (With permission from Berthold and Carlstedt, 1977b.)

tissue, including Schwann cells, fibroblasts, pericytes, and collagen (Berthold and Carlstedt, 1977a). Schwann cells enveloping the most proximal PNS axon segment lie in an invagination of the glia limitans (see Fraher, 1992). At the site of CNS-PNS transition the basal lamina of the Schwann cell is continuous with the basal lamina of the glia limitans, and both unmyelinated and myelinated axons are surrounded by astrocytic process as they traverse the TZ (Fraher, 1992). Most unmyelinated PNS axons continue as unmyelinated axons into the CNS compartment. Where a bundle of unmyelinated axons is about to cross the CNS-PNS borderline, the Schwann cell cytoplasm surrounding the PNS axons attenuates and terminates (Carlstedt, 1977). At the point of transition, some axons may be covered partly by Schwann cell cytoplasm and partly by astrocytic cytoplasm. Other axons lose their Schwann cell sheaths a few micromillimeters distal to the CNS-PNS borderline and are covered only by a basal lamina. Unmyelinated PNS axons with diameters of 0.6 to 0.8 |im or more become myelinated as they enter the CNS (Carlstedt, 1977). Myelinated fibers have a transitional node at the CNS-PNS interface. Such nodes are bordered by a CNS and a PNS myelin sheath and exhibit a mixture of CNS and PNS features (Fig. 20B). Node density is very high in the TZ. In the TZ of rat, lumbar ventral rootlets the node density is 7 times that in the ventral root and more than twice that in the intramedullary rootlet (Fraher and Bristol, 1990). In addition, Marchi-positive myelinoid bodies are clearly more frequent here than in white matter in general and much more frequent than on the PNS side of the TZ (Corneliuson et al., 1989).

After a crush lesion of a dorsal root in an adult rat the axons regenerate toward the spinal cord, but they stop at the TZ (Fraher and Dockery, 2002). Embryonic human dorsal root ganglion (DRG) neurons, which have been implanted into adult rat DRGs, emit axons into the dorsal rootlets. These axons can enter the CNS, but axon density decreases abruptly when the TZ is approached. This suggests that adult as well as embryonic neurons are sensitive to some growth inhibitory factor(s) emanating from the TZ (Kozlova et al., 1997). These and other similar experiments may eventually promote a more complete understanding of the biology of the PNS-CNS interface, so that we will be able to treat traumatic dorsal root avulsions in the future. With respect to ventral root avulsions, some progress has been made in recent years. Experiments in the cat show that replantation of a divided ventral root into the spinal cord is followed by growth of axons from motoneurons in the ventral horn into the denervated root. Trials in patients show that motor axons can enter implanted ventral roots and grow from the cervical spinal cord into peripheral nerves of the arm, with a resultant useful recovery of motor function (Carlstedt et al., 1995; Fraher, 2000; Carlstedt, 2002). For a more comprehensive discussion of injury-induced changes in the TZ and of regeneration of sensory axons across the

CNS-PNS interface see Cafferty and Ramer (2002) and Fraher and Dockery (2002).

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