| The subependymal zone (SEZ) of the lateral ventricle remains mitotically active in the adult mammalian central nervous system (CNS). Recent studies have demonstrated that this region contains brain stem cells in adult rodents. We have used immunohistochemistry to examine a variety of neuronal (TuJ1, NADPH-diaphorase, neuron specific enolase), glial (RC-2, vimentin, glial fibrillary acidic protein (GFAP), and galactocerebroside), extracellular matrix (tenascin-C, chondroitin sulfate, and a chondroitin sulfate proteoglycan named DSD-1-PG), stem cell (nestin) and proliferation (BrdU, histone) markers in the SEZ with the hope of understanding factors that may affect neuronal proliferation and migration from this region throughout development and in adulthood. Also, cell death occurring in the SEZ was analyzed using nick end labeling and flow cytometry techniques. Cultures of the SEZ using explant and suspension techniques were performed. Finally, tissue transplantation and in vivo manipulations were made to determine the potential of the SEZ in cell replacement paradigms.; TuJ1 and BrdU immunocytochemistry revealed that proliferative neurons persist in the SEZ in adulthood which are immature by both morphological and immunohistochemical criteria. The persistence of glial-derived extracellular matrix molecules such as tenascin and chondroitin sulfate proteoglycans (as well as other “boundary” molecules) and the GFAP positive reactive astrocytes that express them in the adult SEZ demonstrated that this region more closely resembles the developing rather than mature brain. Also, while cells are proliferating in this region, few cells are dying, suggesting that in fact they are capable of maturing and integrating with other cells in the mature CNS. Culture studies demonstrated not only that pluripotential stem cells exist in the mature CNS, but that this region can be manipulated to induce extensive neuron production. Cell transplantation studies, as well as in vivo manipulations, suggested that these cells may be useful in cell replacement paradigms. Finally, we have taken the information learned from the rodent studies and demonstrated that a similar region persists in the mature human brain. The implications for clinical neurobiology are reviewed. |
