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Many studies have shown that, the neural stem cells at the hippocampus, ependyma, subependyma and choroid plexus, subependymal region, cerebral cortex of the lesioned site and contralateral hippocampus region may proliferate, migrate, and differentiate into neurons and astrocyte when cerebral ischemia injury occurs^[1-2], so as to compensate and repair the damaged nerve tissues, these neural stem cells can bring hope for neurological functional recovery. The neurogenesis in the adult brain is affected by the regulation of many factors, such as age, chronic stress, depression, growth factor and brain damage, etc., among them the growth factors is the most important environmental factor. Insulin-like growth factor-1 (IGF-1) is a peptide hormone, it has proven to promote the proliferation of precursor cells^[3]. In this study, the IGF-1 was given into rats through tail vein, to observe the influence of IGF-1 on the proliferation, migration and differentiation of neural stem cells after cerebral ischemia.

In 2000, Gage et al ^[7] have pointed out the characteristics of neural stem cells in Science: ① able to differentiate into neural tissue or are derived from the nervous system; ② self-renewing capacity; ③ generate new cells through asymmetric division. The neurogenesis in adult mammals (including humans) mainly exists in two separate areas: ventricular zone and subventricular zone, hippocampal dentate gyrus^[8]. Growth factor is an essential environmental factor of neural stem cells in the process of survival and differentiation, it is a kind of peptide molecules to stimulate cell division, the growth factor-related neurotrophic factors and their tyrosine kinase receptors play an important role in determining the neural stem cells and neuron development. IGF-1 is one member of insulin-like growth factor family, it acts through the IGF-1R function, IGF-1R has the activity of intrinsic tyrosine kinase^[9]. Studies have shown that neural stem cells proliferated firstly in the SGZ after cerebral ischemia, and then moved to the GCL to differentiate into neurons and glial cells, the process takes about 2 months^[2]. In this study, the experimental rats were treated with tail vein injection of IGF-1, then the number of BrdU (+) cells and PSA-NCAM (+) cells were observed to be the most at 7 days after ischemia, the BrdU and PSA-NCAM double-labeled cells were detectable in bilateral subependymal zone and hippocampus dentate gyrus at 4 days and reached the peak at 7 days, followed by gradual reduction; while BrdU and MAP2, as well as BrdU and GFAP double-labeled cells significantly increased from 14 days, compared with previous findings, tail vein injection of IGF-1 in rats after cerebral ischemia could promote the proliferation, migration and differentiation of neural stem cell at different degrees; In addition, in the experimental group and control group, the number of BrdU-labeled positive cells, PSA-NCAM-labeled positive cells, BrdU PSA-NCAM double-labeled-positive cells, BrdU MAP2 double-positive cells were significantly different with different nerve points, indicating that the tail vein injection of IGF-1 can promote the proliferation, migration and differentiation of neural stem cells in rats after cerebral ischemia, we can see that tail vein injection of IGF-1 is conducive for the rehabilitation of neurological function after cerebral ischemia. After cerebral ischemia, neural stem cells are shown to proliferate in the lateral ventricles, hippocampus and cortex at the ischemic side, the proliferation and differentiation are also seen in the contralateral hippocampal dentate gyrus SGZ, suggesting that cerebral ischemia caused neural stem cell proliferation, does not result from the ischemic stimulus, which may only be an incentive, while growth factor and its signaling pathway may be the main reason to change, cell proliferation is not consistent with the occurrence of ischemic stimulus, but reaches the peak after a period of time when the ischemic stimulus stops, this time period is just the time of micro-environmental factors after stimulus, local application of growth factor can play a catalytic role in the proliferation of human neural stem cells, by reverse, the growth factor is considered as the most important environmental factors. At present, the research regarding endogenous neural stem cells has no substantive breakthrough, the specific functions remains poorly understood, even their location and migration process^[10] as well as its potential mechanism are not clear.

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