The relationship between injury and repair of the central nervous system is complex. Although long considered incapable of regeneration, the mammalian central nervous system can undergo neurogenesis and gliogenesis re-establishing axon–glial interactions needed for remyelination and safe conduction of the nerve impulse. In health, glia and neurons each exert survival effects on other constituents of the developing and mature central nervous system. Microglia mediate cell injury when activated but damaged tissue may be advantaged by the inflammatory process which delivers growth promoting and neuroprotective molecules to sites of tissue injury. Furthermore, bystander damage is limited whilst degenerate material is removed.

Myelination

Stem cells

Stem cells self-replicate through asymmetric division and differentiate down a variety of fate-committed lineages. They can be identified by surface markers or the behaviour of their progeny in defined environments. The principal source of neural stem cells during development is subventricular zone ependymal cells (Fig. 97.1, see colour plate section). Adult neural stem cells are present especially in the hippocampus and olfactory bulb but also in the neocortex (Maglivi et al., 2000). Embryonic stem cells are even less restricted retaining the ability to maintain the germline and differentiate to a cell-specific fate such as oligodendrocytes or dopaminergic neurons (Thompson et al., 1998). The need to select survivors from cells overproduced in the developing nervous system involves programmed cell death. Caspases cleave proteins supporting the nuclear membrane and cause apoptosis by activation of the endonuclease which digests DNA. Programmed cell death is influenced by the mammalian mitochondrial product Bcl-2 and other antiapoptotic (Bcl-X) and proapoptotic molecules (Bax, Bad and Bid). Apoptosis makes it safe to retain a source of mitotic precursors in the mature nervous system, whilst avoiding uncontrolled growth.

Growth factors for neurones and glia

Acting together or in sequence, growth factors orchestrate development within the nervous system influencing proliferation, migration and differentiation. Many also support survival of fully differentiated cells.

Retinoic acid promotes embryonic cell differentiation down the neural lineage. Further in vitro manipulations yield mixed cultures enriched for oligodendrocytes (Brustle et al., 1999). Murine neural stem cells proliferate in response to epidermal growth factor (EGF).