However, the role of glia in E2 neuroprotection requires further study as a recent study using neuron-specific and microglia-specific ERα knockout mice found that E2 neuroprotection in the cerebral cortex against focal cerebral ischemia was markedly attenuated only in the neuron-specific ERα knockout mice and not in the microglia-specific ERα knockout mice, suggesting that E2 may in part, act directly upon neurons to exert neuroprotection against ischemia [52]. This evidence concerns the gene ESR1 and ischemia.