Effects of Scutellaria baicalensis on neurogenesis in the hippocampal dentate gyrus and on spatial memory of adult rats

We investigated the effects of ethanol extracted Scutellaria baicalensis（EESB） on spatial memory function and neurogenesis in the hippocampal dentate gyrus.Adult Sprague-Dawley rats were orally administered 50,100,or 200 mg/kg of EESB for 6 successive days.The radial-arm maze test showed that 200 mg/kg of EESB improved the spatial memory of adult rats.Confocal microscopy results showed that 100 mg/kg of EESB increased the number of bromodeoxyuridine（BrdU）-and neuron-specific nuclear protein-positive cells in the granular cell layer,and that 100 and 200 mg/kg of EESB increased the number of BrdU-/neuron-specific nuclear protein-positive cells in the sub-granular zone.200 mg/kg of EESB increased the number of BrdU-/glial fibrillary acid protein-positive cells in the subgranular zone.These findings indicate that EESB can effectively promote neurogenesis in the hippocampal dentate gyrus and improve spatial memory function.

Time-dependent effect of combination therapy with erythropoietin and granulocyte colony-stimulating factor in a mouse model of hypoxic-ischemic brain injury

Erythropoietin （EPO） and granulocyte colony- stimulating factor （G-CSF） are likely to play broad roles in the brain. We investigated the effects of combination therapy with EPO and G-CSF in hypoxic- ischemic brain injury during the acute, subacute, and chronic phases. A total of 79 C57BL/6 mice with hypoxic-ischemic brain injury were randomly assigned acute （days 1-5）, subacute （days 11-15）and chronic （days 28-32） groups. All of them were treated with G-CSF （250 μg/kg） and EPO （5 000 U/kg） or saline daily for 5 consecutive days. Behavioral assessments and immunohistochemistry for angiogenesis, neuro- genesis, and astrogliosis were performed with an 8-week follow-up. Hypoxia-inducible factor-1 （HIF-1） was also measured by Western blot analysis. The results showed that the combination therapy with EPO and G-CSF in the acute phase significantly improved rotarod performance and forelimb-use symmetry compared to the other groups, while subacute EPO and G-CSF therapy exhibited a modest improvement compared with the chronic saline controls. The acute treatment significantly increased the density of CD31^＋（PECAM-1） and a-smooth muscle actin^＋ vessels in the frontal cortex and striatum, increased BrdU^＋/PSA- NCAM^＋ neurogenesis in the subventricular zone, and decreased astroglial density in the striatum. Furthermore, acute treatment significantly increased the HIF-1 expression in the cytosol and nucleus, whereas chronic treatment did not change the HIF-1 expression, consistent with the behavioral outcomes. These results indicate that the induction of HIF-1 expression by combination therapy with EPO and G-CSF synergistically enhances not only behavioral function but also neurogenesis and angiogenesis while decreasing the astroglial response in a time- dependent manner.