Extracellular matrix (ECM) molecules, including chondroitin-4 or chondroitin-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 paradigm to assess the effects of these wound-associated molecules on embryonic dopamine cell attachment and neurite outgrowth. Light and electron microscopic immunocytochemistry studies have shown that astroglial 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 graft-scar interactions. Explants from the wounded striatum taken at different 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 relation to the expression of both CSPG and tenascin. The increase in neuronal attachment in this paradigm, however, is accompanied by a postlesion survival time-dependent significant decrease in neuritic growth from these cells. In vitro ECM antibody treatment suggests that CSPG may be responsible for heightened dopamine cell attachment and that tenascin simultaneously may support cell attachment while inhibiting neurite growth. The present study offers a new approach for the in vitro analysis of cell and molecular interactions after brain injury and brain grafting, in essence acting as a nigrostriatal transplant-in-a-dish.
The presence of WT1 in glioma cell lines and the majority of primary tumor samples and its absence in normal astrocytes support the suggestion that WT1 expression is important in glioma biology.
The ability to enhance the radiosensitivity of malignant glioma cells that express wild-type p53 by using adenoviral transduction to induce overexpression of p53 offers hope for this approach as a therapeutic strategy, not only in human gliomas that express mutant p53, but also in those that express wild-type p53.
The authors found that PS-ODNs can be safely delivered in high concentrations to wide areas of rat brain by using high-flow microinfusion and are stable even after 48 hours in situ.
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