Neuron-Glia Ensembles and Mammalian CNS Lesion Repair

Abstract

Damage to the CNS breaks the physical and functional boundaries of the nervous tissue, disrupts the interactions between neural cells, and destroys both the neurons and the connections in which they are involved. At the beginning of the century, Cajal showed that damaged CNS did not regenerate spontaneously, an observation supported by subsequent morphological studies. However, at the same time, it was observed that adult CNS “rejuvenated” in response to injury. Mechanical trauma, stroke and many degenerative diseases, evoke developmental capabilities in the adult CNS, such as glial proliferation and differentiation, axonal sprouting and synaptogenesis. CNS response to injury is best understood as the response of neuron-glia ensembles. These ensembles have properties that, unaided, are capable of correcting minor CNS lesions. We believe that, adequately controlled, these properties could also permit to correct the consequences of major CNS injury. True regeneration, i.e. the restitution of the CNS to its pre-injury state, is clearly impossible in the absence of neuronal division. However, we think that functional repair can be achieved. The present chapter describes, within the above context, the work carried in our laboratory regarding: i) Brain inhibitors of astrocyte and astrocytoma proliferation, ii) Inhibitors of neurite outgrowth in reactive glia and iii) Enhancement of nerve fiber regeneration by olfactory bulb ensheathing glia.