The temporal and spatial changes of microtubule cytoskeleton in the CA1 stratum radiatum following global transient ischemia

The down-regulation of microtubule proteins has been widely documented in the ischemic brain, but the temporal or spatial alteration of microtubules has not been systematically investigated in the vulnerable areas after ischemia. By examining the stability and distribution of microtubules following transient global ischemia, we found that the biomarkers of stable microtubules, MAP2 and acetylated alpha-tubulin, became significantly downregulated in the CA1 stratum radiatum of rat hippocampus and that the neuron-specific microtubule protein, class III beta-tubulin, was progressively decreased in the same region. Surprisingly, pan-beta-tubulin, which is expressed at a low level in glial cells under physiological conditions, was significantly increased in reactive astrocytes after ischemia. The finding was supported by protein quantification and confocal microscopy analysis, and consistent with the different vulnerabilities of neuronal and glial cells to the ischemic insult. To our knowledge, the different responses of microtubules between neuronal and glial cells have not been described in the ischemic brain before. The deconstruction of microtubules in the neurons is expected to contribute to the selective and delayed neuronal death in the vulnerable brain regions, while the increased microtubules in the reactive astrocytes may play an important role in the shape conversion of astrocytes induced by ischemia.