Differential Sensitivity of Murine Astrocytes and Neurons from Different Brain Regions to Injury

Abstract

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 neuronal 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 hippocampus (59.8 ± 4.8%), and least in cortex (37.0 ± 3.5%). In contrast neurons 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 greater in cortical neurons than in those from striatum or hippocampus, while excitotoxic neuronal injury was equivalent between regions. Antioxidant status and apoptosis-regulatory genes were measured to assess possible underlying differences. Glutathione was higher in astrocytes and neurons isolated from striatum than in those from hippocampus. Superoxide dismutase activity was significantly higher in striatal astrocytes, while glutathione peroxidase activity and superoxide did not differ by brain region. Bcl-xL was significantly higher in striatal astrocytes than in astrocytes from other brain regions and higher in striatal and hippocampal neurons than in cortical neurons. Both neurons and astrocytes isolated from different brain regions demonstrate distinct patterns of vulnerability when placed in primary culture. Antioxidant state and levels of expression of bcl-xL can in part account for the differential injury observed. This suggests that different protective strategies may have different efficacies depending on brain region.