Neuroprotective effect of ischemic preconditioning in focal cerebral infarction: relationship with upregulation of vascular endothelial growth factor

Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a transient ischemic attack twice （each a 20-minute occlusion of the middle cerebral artery） before inducing focal cerebral infarction （2 hour occlusion-reper- fusion in the same artery）. We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after ocdusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascu- lar endothelial growth factor.

Expression and Clinical Significance of Vascular Endothelial Growth Factor in Benign and Malignant Tissues of Breast

Objective： To detect the expression of vascular endothelial growth factor （VEGF） and microvessel density （MVD） count in breast benign affection, breast atypical hyperplasia and breast carcinoma in situ, and to clarify the relationship between VEGF expression, MVD and the clinicopathological features of these diseases. Methods： The expression of VEGF and MVD count in 115 cases breast benign diseases （including 40 breast fibroid tumor, 40 breast cystic hyperplasia and 35 intraductal papilloma, 19 breast atypical hyperplasias and 32 breast carcinomas in situ were examined by immunohistochemistry staining （SP-method）. Results： The positive rate of VEGF in breast benign diseases, breast atypical hyperplasia and breast carcinoma in situ were 21.74%（25/115）, 31.58.% （6/19）and 53.13%（17/32） respectively. It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The expression of VEGF increased gradually in the three groups （P〈0.05）. The MVD count of the three groups were 14.41 ± 2.59, 18.89± 4.47 and 21.13 ± 4.12 respectively, It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The MVD count of the three groups increased gradually （P〈0.05）. In VEGF positive group, MVD count was 19.41 ±4.78; In VEGF negative group, MVD count was 14.91±3.15. The MVD count was higher in VEGF positive group than that in VEGF negative group （P〈0.05）. Conclusion： The results of this study suggested that VEGF could promote microvessel growth in breast tumors. The occurrence and progression of breast cancer might be related with the expression of VEGF.

Optimal duration of percutaneous microballoon compression for treatment of trigeminal nerve injury

Percutaneous microballoon compression of the trigeminal ganglion is a brand new operative technique for the treatment of trigeminal neuralgia. However, it is unclear how the procedure mediates pain relief, and there are no standardized criteria, such as compression pressure, com- pression time or balloon shape, for the procedure. In this study, percutaneous microballoon compression was performed on the rabbit trigeminal ganglion at a mean inflation pressure of 1,005 ＋ 150 mmHg for 2 or 5 minutes. At 1, 7 and 14 days after percutaneous microballoon compression, the large-diameter myelinated nerves displayed axonal swelling, rupture and demy- elination under the electron microscope. Fragmentation of myelin and formation of digestion chambers were more evident after 5 minutes of compression. Image analyzer results showed that the diameter of trigeminal ganglion cells remained unaltered after compression. These experi- mental findings indicate that a 2-minute period of compression can suppress pain transduction. Immunohistochemical staining revealed that vascular endothelial growth factor expression in the ganglion cells and axons was significantly increased 7 days after trigeminal ganglion compression, however, the changes were similar after 2-minute compression and 5-minute compression. The upregulated expression of vascular endothelial growth factor in the ganglion cells after percu- taneous microballoon compression can promote the repair of the injured nerve. These findings suggest that long-term compression is ideal for patients with recurrent trigeminal neuralgia.

Vascular Endothelial Growth Factor and Cluster of Differentiation 34 for Assessment of Perioperative Bleeding Risk in Gastric Cancer Patients

Background： Angiogenesis is the formation of new blood vessels to supply nutrients to tumors. Vascular endothelial growth factor （VEGF） and cluster of differentiation 34 （CD34） are important signaling proteins involved in angiogenesis. Many studies have demonstrated that VEGF and CD34 are related to tumor progression. This study focused on the relationship between VEGF, CD34, and perioperative hemorrhage in patients with gastric cancer. Methods： To observe the relationship between VEGF and CD34, we tracked 112 patients with advanced gastric cancer for 5 years to assess factors related to hemorrhage, using immunohistochemistry. The results were subjected to statistical analysis using a 2 × 2 contingency table, logistic regression, and receiver operating characteristic （ROC） test. Results： The concentrations of VEGF and CD34 were critically correlated with perioperative hemorrhage and neural invasion in patients with gastric cancer （P 〈 0.05）. Expression of VEGF and CD34 was related （P 〈 0.05, χ2 = 6.834）. VEGF and CD34 co-expression strongly increased the risk of preoperative bleeding （area under the ROC curve 〉0.7, P 〈 0.05）. Conclusions： Expression of VEGF and CD34 was critically correlated with perioperative hemorrhage in gastric cancer patients. Co-expression of VEGF and CD34 could be an effective indicator for evaluating the risk ofperioperative bleeding in gastric cancer patients.

Evidence for a therapeutic effect of Braintone on ischemic brain damage

This study used a novel combination of in vivo and in vitro experiments to show that Braintone had neuroprotective effects and clarified the molecular mechanisms underlying its efficacy. The Chinese herbal extract Braintone is composed of Radix Rhodiolase Essence, Radix Notoginseng Essence, Fofium Ginkgo Essence and Rhizoma Chuanxiong. In vivo experiments showed that cerebral infarction volume was reduced, hemispheric water content decreased, and neurological deficits were alleviated in a rat model of permanent middle cerebral artery occlusion after administration of 87.5, 175 or 350 mg/kg Braintone for 7 consecutive days. Western blot analysis showed that Braintone enhanced the expression of hypoxia-inducible factor la, heme oxygenase-1 and vascular endothe- lial growth factor in the ischemic cortex of these rats. The 350 mg/kg dose of Braintone produced the most dramatic effects. For the in vitro experiments, prior to oxygen-glucose deprivation, rats were intragastrically injected with 440, 880 or 1 760 mg/kg Braintone to prepare a Braintone-co ntaining serum, which was used to pre-treat human umbilical vein endothelial cells for 24 hours. Human umbilical vein endothelial cell injury was alleviated with this pre-treatment. Western blot and real-time PCR analysis showed that the Braintone-containing serum increased the levels of hy- poxia-inducible factor la mRNA and protein, heine oxygenase-1 protein and vascular endothelial growth factor mRNA in oxygen-glucose deprived human umbilical vein endothelial cells. The 1 760 mg/kg dose produced the greatest increases in expression. Collectively, these experimental findings suggest that Braintone has neuroprotective effects on ischemia-induced brain damage via the up-regulation of hypoxia-inducible factor la, heme oxygenase-1 and vascular endothelial growth factor expression in vascular endothelial cells.