The role of metallothionein and astrocyte-neuron interactions in injury to the CNS

The physiological role of metallothionein (MT) has been a topic of growing interest, particularly with regard to a potential therapeutic application in trauma of the central nervous system (CNS). An increasing number of studies describe the protective, regenerative, and anti-inflammatory properties of MT-I and MT-II isoforms (MT-I/MT-II) in the context of in vitro and animal models, using, for example, MT-I/MT-II null, overexpressing, or injected mice following induced CNS trauma or disease. MT-I/MT-II respond to trauma by upregulation, and may have roles in metal ion homeostasis and free radical scavenging. Notably, a direct action of MT-I/MT-II on neurons has been shown using in vitro models, whereby the application of exogenous MT-I/MT-II directly increases neurite outgrowth of young neurons and regeneration of injured, mature neurons. The expression and putative functions of MT within the injured CNS will be addressed within this chapter, with particular regard to the MT-I/MT-II isoforms that display neuroprotective and regenerative properties. Intriguingly, a further member of the MT family, MT-III, shows high homology to MT-I/MT-II, yet has a contrasting effect on neuron growth and survival in some models.