CHONDROITIN SULFATE PROTEOGLYCAN AND TENASCIN IN THE WOUNDED ADULT-MOUSE NEOSTRIATUM IN-VITRO - DOPAMINE NEURON ATTACHMENT AND PROCESS OUTGROWTH

Extracellular matrix (ECM) molecules, including chondroitin-4, or chon droitin-6 sulfate proteoglycans (CSPGs) and tenascin, are upregulated in and around wounds and transplants to the adult CNS. In the present study, striatal wounds from adult mice were used in a novel in vitro p aradigm to assess the effects of these wound-associated molecules on e mbryonic dopamine cell attachment and neurite outgrowth. Light and ele ctron microscopic immunocytochemistry studies have shown that astrogli al scar constituents persist in cultured explants for at least 1 week in vitro, and despite the loss of neurons from adult striatal explants , there is a retention of certain structural features suggesting that the wound explant-neuron coplant is a viable model for analysis of gra ft-scar interactions. Explants from the wounded striatum taken at diff erent times after a penetrating injury in vivo were used as substrates for embryonic ventral mesencephalon neurons that were plated on their surfaces. Dopamine cell attachment is increased significantly in rela tion to the expression of both CSPG and tenascin. The increase in neur onal attachment in this paradigm, however, is accompanied by a postles ion survival time-dependent significant decrease in neuritic growth fr om these cells. In vitro ECM antibody treatment suggests that CSPG may be responsible for heightened dopamine cell attachment and that tenas cin simultaneously may support cell attachment while inhibiting neurit e growth. The present study offers a new approach for the in vitro ana lysis of cell and molecular interactions after brain injury and brain grafting, in essence acting as a nigrostriatal transplant-in-a-dish.