| The aim of this dissertation is to test the hypotheses (1) that transplantation of fetal kidney cells may elicit neuroprotection during cerebral ischemia, (2) that endogenous GDNF, upregulated by pharmacological manipulation, may protect brain against ischemia-induced brain injury, (3) that the GDNF is the key factor in fetal kidney cell-induced neuroprotection, (4) that transplanted fetal kidney cells may be an endogenous source of GDNF and other trophic factors for regenerating the nigrostriatal pathway, and (5) that progenitor cells from embryonic rat brain are indeed multipotent neural stem cells.; Transplantation of fetal kidney cells reduced the volume of cortical infarction and restored behavioral deficits in adult rats. Systemic administration of vitamin D3 for 8 days increased cortical GDNF levels and decreased ischemia-induced brain infarction. Since there are no GDNF receptor (GFRα1) antagonists, the neuroprotective mechanism of GDNF and the efficacy of intracerebral kidney cell transplants were examined in heterozygous GFRα1 null mutated (+/−) and wildtype (+/+) mice. GDNF administration and fetal kidney cell implantation decreased the motor deficits and cortical infarction induced by stroke in +/+ mice but not in +/− mice. Nigrostriatal transplantation of fetal kidney cells helped to regenerate dopaminergic fibers in the pathway of hemiparkinsonian rats. The neural stem cells from embryonic rat brain were undifferentiated, proliferative and capable of self-renewal over 2 years in vitro. After being transferred to an appropriate environment, they differentiate into neurons, astrocytes and oligodendrocytes. Their differentiation fates were affected by epigenetic factors. |
