Journal
EXPERIMENTAL NEUROLOGY
Volume 221, Issue 1, Pages 98-106Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2009.10.006
Keywords
Traumatic brain injury; Astrogliosis; Regeneration
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Funding
- Australian Research Council [LP0774820]
- Bestenbalt LLC (Estonia)
- Discovery project grants [DP0556630, DP0984673]
- Jack & Ethel Goldin Foundation
- National Health & Medical Research Council [254670, 352623]
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Following central nervous system injury, astrocytes rapidly respond by undergoing a stereotypical pattern of molecular and morphological alterations termed reactive astrogliosis. We have reported previously that metallothioneins (MTs) are rapidly expressed by reactive astrocytes and that their secretion and subsequent interaction with injured neurons leads to improved neuroregeneration. We now demonstrate that exogenous MT induces a reactive morphology and elevated GFAP expression in cultured astrocytes. Furthermore, these astrogliotic hallmarks were mediated via JAK/STAT and RhoA signalling pathways. However, rather than being inhibitory, MT induced a form of astrogliosis that was permissive to neurite outgrowth and which was associated with decreased chondroitin sulphate proteoglycan (CSPG) expression. The results suggest that MT has an important role in mediating permissive astrocytic responses to traumatic brain injury. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved.
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