Abstract：In the neuroscience, the neuron doctrine has been considered as the gold standard for more than 100 years. In the meantime, unfortunately, the achievements during past several decades have been proved to be far away from what would have been expected: the mystery of human's memory and emotion is still an open question, and the Alzheimer's disease and the stroke etc. still cause the disability and crush the dignity of human beings. Although Claude Bernard had stressed the importance of the internal environment 150 years before, not much attention has been paid to the micro-environment around neurons (brain extracellular space), although this space occupies about 20% of the brain volume in vivo. The significance of the micro-environment of neurons is emphasized in this paper based on a review and analysis of the unsuccessful investigations on neuro-protective agents against cerebral ischemic stroke. The defects of neuron's doctrine are discussed. The nature of the micro-enviorment around neurons is a neglected issue in the neuroscience for a long time and it will be an indispensable complement of the neuron's doctrine.