Differential sensitivity of murine astrocytes and neurons from different brain regions to injury

Different brain regions show differential vulnerability to ischemia in vivo . Despite this, little work has been done to compare vulnerability of brain cells isolated from different brain regions to injury. Relatively pure neu ronal and astrocyte cultures were isolated from mouse cortex, hippocampus, and striatum, Astrocyte vulnerability to 6 h oxygen-glucose deprivation was greatest in striatum (81.8 +/- 4.6% cell death), intermediate in hippocamp us (59.8 +/- 4.8%), and least in cortex (37.0 +/- 3.5%). In contrast neuron s deprived of oxygen and glucose for 3 h showed greater injury to cortical neurons (71.1 +/- 5.2%) compared to striatal (39.0 +/- 3.1%) or hippocampal (39.0 +/- 5.3%) neurons. Astrocyte injury from glucose deprivation or H2O2 exposure was significantly greater in cells from cortex than from striatum or hippocampus. Neuronal injury resulting from serum deprivation was great er in cortical neurons than in those from striatum or hippocampus, while ex citotoxic neuronal injury was equivalent between regions. Antioxidant statu s and apoptosis-regulatory genes were measured to assess possible underlyin g differences. Glutathione was higher in astrocytes and neurons isolated fr om striatum than in those from hippocampus, Superoxide dismutase activity w as significantly higher in striatal astrocytes, while glutathione peroxidas e activity and superoxide did not differ by brain region. Bcl-x(L) was sign ificantly higher in striatal astrocytes than in astrocytes from other brain regions and higher in striatal and hippocampal neurons than in cortical ne urons. Both neurons and astrocytes isolated from different brain regions de monstrate distinct patterns of vulnerability when placed in primary culture . Antioxidant state and levels of expression of bcl-x(L) can in part accoun t for the differential injury observed. This suggests that different protec tive strategies may have different efficacies depending on brain region. (C ) 2001 Academic Press.