Background: Newborns with moderate to severe hypoxic ischemic encephalopathy benefit from treatment with whole body hypothermia. Cellular and molecular mechanisms through which hypothermia causes neuroprotection have not completely elucidated yet. We hypothesize that hypothermia causes overexpression of neurotrophic factors and thus prevents or decrease neuronal apoptosis. Objective: Goal of this study was to investigate the effects of hypoxia and hypothermia on neurotrophic factor gene expression in human fetal brain cells using RT-PCR array analysis. Design/Methods: Human fetal brain cells were obtained from 18 week gestation abortus. Fetal brain cells were divided in three culture conditions. Cells in normothermia (37 C) and Normoxia were in control conditions. Cells in hypoxia chamber at 1% oxygen for 24 hours followed by normothermia were hypoxic & normothermic . Cells in Hypoxia followed by hypothermia (33 C) for 72 hours were hypoxic & hypothermic . RNA extraction, CDNA synthesis followed by RT-PCR arrays were performed for each culture conditions. Results: When gene expression patterns of hypoxic & normothermic cells were compared to hypoxic &hypothermic cells, Brain Derived Neurotrophic factor (BDNF) upregulation and Artemin (Glial Cell Derived Neurotrophic factor superfamily ligand) down regulation was noted. When Hypoxic & hypothermic cells were compared to cells in control conditions impressive upregulation of IL10 and BDNF gene regulation was noted. The BDNF gene upregulation was confirmed after RT-PCR analysis was repeated with BDNF gene only in triplicates. Conclusion: Neuroprotective effects of therapeutic hypothermia may be mediated through upregulation of BDNF and down regulation of Artemin. Additional studies are warranted to further define neuroprotective physiology of therapeutic hypothermia.