Abnormal blood flow in the placenta, leading to hypoxia or reperfusion is linked to damage to the foetal brain and may occur in a variety of conditions including miscarriage, pre eclampsia and intrauterine growth restriction (1). This may lead to lifelong disability ranging from cerebral palsy to Autism spectrum disorders. Our data shows that hypoxia reperfusion of a cellular model of the placenta induces the release of toxic factors that damage neurons and astrocytes in cortical cultures. In vitro barriers that model the placenta were made from BeWo cells and exposed to various concentrations of oxygen (2%, 2-8%, 2-12%, 2-21%, 21%) and the tissue culture media was collected as conditioned media (CM). Dissociated neurons from rat E18.5 cortical cultures were grown for 12 days before being exposed to CM for 6 days. Hippocampal slices were also taken from P7 rats and grown as organotypic cultures for 14 days before being exposed to CM for 6 days. Cultures/ hippocampal slices were then fixed and fluorescently stained with MAP2 and GFAP to identify the neuronal and astrocyte cell populations. Images were captured using confocal microscopy and cell morphology was analysed using ImageJ. Flow cytometry analysis (LSRII) was also performed on cortical cultures to analyse the effects of the CM on cell death, cell cycle, mitochondrial free radicals and autophagy. Both culture models showed similar results. Control conditions (21% oxygen) showed good neuronal growth and the astrocytes had long process with many branch points and end plates. In cultures that were exposed to hypoxic (2%) CM, there was poor neuronal growth with blebbing. Similarly astrocytes were reduced in number showing a distinct change in morphology with very few processes. Exposure to CM after re-oxygenation (2-8% and 2-21% oxygen) also caused poor neuronal outgrowth. However the astrocytes were increased in number and well branched (2-8% vs 2% and 2-21% vs 2%). These results show that in CM produced in 2% oxygen there are harmful molecules released from trophoblast that damage neurons and astrocytes. Neuronal damage is seen using hypoxic and re-oxygenated CM where as astrocytes appear to be mainly affected by the hypoxic (2% oxygen) CM. Thus, when a hypoxic condition is sustained there is dendritic shortening in neurons and morphological changes in astrocytes. The reduction in process length and cell volume in astrocytes could lead to a reduced contact between neurons and astrocytes. Abnormal signaling between the two cell types results in abnormal neurite outgrowth having an effect on neuronal development, an underlying cause of many neurological diseases. Re-oxygenation does not appear to induce a survival or regenerative affect on the neuronal population in cultures indicating that a therapeutic / pharmacological treatment would be required to overcome any damage from sustained hypoxia.