NEURITE OUTGROWTH INHIBITOR OF GLIOTIC BRAIN-TISSUE - MODE OF ACTION AND CELLULAR-LOCALIZATION, STUDIED WITH SPECIFIC MONOCLONAL-ANTIBODIES

Membranes from injured adult rat brain express a heparan/chondroitin s ulphate proteoglycan that inhibits neurite outgrowth in vitro. We have developed monoclonal antibodies (Mabs) against this proteoglycan, two of which were characterized and used for the study of the inhibitor m ode of action and localization in normal and injured adult brain. The antibodies recognized a molecule of apparent molecular weight 200 kDa in Western blots of injured brain membranes. One of the Mabs blocked b oth the inhibition of neurite outgrowth and the growth cone collapse a ctivity, associated with the proteoglycan. In adult brain, inhibitor i mmunoreactivity was found predominantly in neurons but, after a lesion , it was associated mainly with reactive glial cells. The localization of neurite outgrowth inhibitors in reactive glia supports the idea th at gliotic tissue is largely responsible for the failure of axonal reg eneration in mammalian CNS.