Based on the pathophysiology of the brain, advance in angiogenesis induced by stroke, and evidences of Chinese-medicine-mediated angiogenesis, the possibility to study the stroke-treating mechanism of Chinese medicine in angiogenesis was discussed. And regarding our previous work on angiogenesis modulated by qi-tonifying and stasis-eliminating therapy following intracerebral hemorrhage, we proposed some questions, which should be taken into account in the further work.
Neurogenesis and angiogenesis can improve the neurologic function after intracerebral hemorrhage(ICH).Leukemia inhibitory factor(LIF)plays an important role in neurogenesis and angiogenesis.In this study,a rat model of autologous blood-induced ICH was used to evaluate the effect of LIF on the neurogenesis and angiogenesis following ICH.After ICH,LIF-positive neurons and dilated vessels were detected in the peri-hematomal region.It was found that LIF levels increased significantly and peaked 14 days after ICH induction.Double immunofluorescence confirmed that LIF was expressed in neurons and endothelial cells.ICH also led to increases of doublecortin(DCX)-and von Willebrand factor(vWF)-positive cells as well as proliferation of cell nuclear antigen(PCNA)+/DCX+and PCNA+/vWF+nuclei.All these ICH-induced increases were significantly attenuated by exogenous LIF in fusion.These data suggested that LIF was a negative regulator of neurogenesis and angiogenesis after ICH.
Chuan-zhen LIUHua-jun ZHOUJian-hua ZHONGTao TANGHan-jin CUIJing-hua ZHOUQiang ZHANGZhi-gang MEI
Objective： To investigate the effects of electro-acupuncture on intracerebral hemorrhage （ICH）- induced angiogenesis and hypoxia-inducible factor-1 a （HIF-1 a） expression in rats. Me.otis： Adult male Sprague- Dawley rats were randomly divided into 4 groups of 24 rats each. ICH was induced in 3 groups by stereotactic injection of collagenase type Ⅶ into the right globus pallidus; of these, one group was not further treated, the second group underwent Zusanli （ST36）-acupuncture, and the third group underwent non-acupoint acupuncture. ＇The fourth group underwent sham operations. Acupuncture was performed by stimulation with electrical needles at frequencies of 2-20 Hz for 30 min per day. Angiogenesis on days 3, 7 and 14 was assessed by double iimmunolabeling, and expression of HIF-1 α was evaluated by immunohistochemistry, quantitative real time reverse chain reaction and Westem blotting. Results： 5-Bromo-2-deoxyuddine （BrdU）labeled nuclei in cerebral endothelial cells （ECs） resided around the hematoma and the labeling peaked from 7 to 14 days （P〈0.01）. HIF-1 a positive microvessels with a dilated outline were detected in pedhematomal tissues after ICH, with the vessels extending into the clot from the surrounding area beginning on day 7. Following ICH, HIF-1 a protein levels increased （P〈0.05）, but HIF-1 a mRNA levels did not change. Electro-acupuncture at the Zusanli （ST36） acupoint increased BrdU-labeled nuclei in cerebral ECs （P〈0.05） and up-regulated the expression of HIF-1 a protein （P〈0.05）, but had little effect on the spatial distribution of HIF-1α or on HIF-1α mRNA levels. Conclusions： Electro-acupuncture treatment at the Zusanli （ST36） acupoint may accelerate ICH-induced angiogenesis by up-regulating HIF-1 a protein, and may enhance recovery following hemorrhagic cerebral injury.
