Neuron‐glia communication: metallothionein expression is specifically up‐regulated by astrocytes in response to neuronal injury

Recent data suggests that metallothioneins (MTs) are major neuroprotective proteins within the CNS. In this regard, we have recently demonstrated that MT‐IIA (the major human MT‐I/‐II isoform) promotes neural recovery following focal cortical brain injury. To further investigate the role of MTs in cortical brain injury, MT‐I/‐II expression was examined in several different experimental models of cortical neuron injury. While MT‐I/‐II immunoreactivity was not detectable in the uninjured rat neocortex, by 4 days, following a focal cortical brain injury, MT‐I/‐II was found in astrocytes aligned along the injury site. At latter time points, astrocytes, at a distance up to several hundred microns from the original injury tract, were MT‐I/‐II immunoreactive. Induced MT‐I/‐II was found both within the cell body and processes. Using a cortical neuron/astrocyte co‐culture model, we observed a similar MT‐I/‐II response following in vitro injury. Intriguingly, scratch wound injury in pure astrocyte cultures resulted in no change in MT‐I/‐II expression. This suggests that MT induction was specifically elicited by neuronal injury. Based upon recent reports indicating that MT‐I/‐II are major neuroprotective proteins within the brain, our results provide further evidence that MT‐I/‐II plays an important role in the cellular response to neuronal injury.