Modulating astrogliosis after neurotrauma

Traumatic injury to the adult central nervous system (CNS) results in a rap id response from resident astrocytes, a process often referred to as reacti ve astrogliosis or glial scarring. The robust formation of the glial scar a nd its associated extracellular matrix (ECM) molecules have been suggested to interfere with any subsequent neural repair or CNS axonal regeneration. A series of recent in vivo experiments has demonstrated a distinct inhibito ry influence of the glial scar on axonal regeneration. Here we review sever al experimental strategies designed to elucidate the roles of astrocytes an d their associated ECM molecules after CNS damage, including astrocyte abla tion techniques, transgenic approaches, and alterations in the deposition o f the ECM. In the short term, mediators that modulate the inflammatory mech anisms responsible for eliciting astrogliotic scaring hold strong potential for establishing a favorable environment for neuronal repair. In the futur e, the conditional (inducible) genetic manipulation of astrocytes fields pr omise for further increasing our understanding of the functional biology of astrocytes as well as opening new therapeutic windows. Nevertheless, it is most likely that, to obtain long distance axonal regeneration within the i njured adult CNS, a combinatorial approach involving different repair strat egies, including but not limited to astrogliosis modulation, will be requir ed. (C) 2001 Wiley-Liss, Inc.