Role of metallothionein-III following central nervous system damage

We evaluated the physiological relevance of metallothionein-Ill (NIT-III) in the central nervous system following damage caused by a focal cryolesion onto the cortex by studying Mt3-null mice. In normal mice, dramatic astrogliosis and microgliosis and T-cell infiltration were observed in the area surrounding the lesioned tissue, along with signs of increased oxidative stress and apoptosis. There was also significant upregulation of cytokines/growth factors such as tumor necrosis factor-alpha, interleukin (IL)-1 alpha/beta, and IL-6 as measured by ribonuclease protection assay. Mt3-null mice did not differ from control mice in these responses, in sharp contrast to results obtained in Mt1-Mt2-null mice. In contrast, Mt3-null mice showed increased expression of several neurotrophins as well as of the neuronal sprouting factor GAP-43. Thus, unlike MT-I and MT-II, MT-III does not affect the inflammatory response elicited in the central nervous system by a cryoinjury, nor does it serve an important antioxidant role, but it may influence neuronal regeneration during the recovery process. (C) 2003 Elsevier Science (USA). All rights reserved.