Presentation Title (IN ALL CAPS)

HERBAL FORMULA DANGGUI-SHAOYAO-SAN PROMOTES NEUROGENESIS AND ANGIOGENESIS IN THE RAT FOLLOWING MIDDLE CEREBRAL ARTERY OCCLUSION

Departmental Affiliation and City, State, Zip for All Authors

Brian Wang (Center for Neuroscience Discovery, Institute for Healthy Aging, Fort Worth, TX 76107); Ning Li (Institute of Hypoxia Medicine, Beijing 100053); Kunlin Jin (Center for Neuroscience Discovery, Institute for Healthy Aging, Fort Worth, TX 76107); Xunming Ji (Institute of Hypoxia Medicine and Department of Neurosurgery, Beijing 100053); Changhong Ren (Institute of Hypoxia Medicine, Beijing 100053, and Center for Neuroscience Discovery, Institute for Healthy Aging, Fort Worth, TX 76107)

Classification

GSBS Student (For Competition)

Research Presentation Category

Basic Science Research

Brief Narrative or Summary

Ischemic stroke is an age-related disease and is the lead cause of disability worldwide. It currently has only one FDA-approved treatment on the market. Unfortunately, just 1-2% of stroke patients benefit from the drug because it does not seem to be very effective after 4.5 hours from when stroke symptoms occur. Therefore, it is critical to find another form of treatment that will be beneficial for stroke patients even days or weeks after stroke has taken place. In fact, many studies found that promoting the growth of new brain cells and blood vessels after stroke proved to be an excellent strategy for alleviating brain injury.

The traditional Chinese medication, Danggui-Shaoyao-San (DSS), is used widely in oriental countries such as China, Korea, and Japan to relieve menstrual disorder and other abdominal pains of women. Recent studies have also shown that it could reduce brain injury and increase blood flow in the brains of animals after stroke. Thus, DSS seems to be a potential treatment for stroke but the precise mechanism by which it reduces brain injury is still unknown.

Our work demonstrates for the first time that Danggui-Shaoyao-San lessens brain injury by increasing the birth of new brain cells and blood vessels significantly after stroke, suggesting that DSS is a suitable and potential treatment even weeks after the occurrence of stroke.

Scientific Abstract

Studies show that the traditional Chinese medication, Danggui-Shaoyao-San (DSS), is not only beneficial for menstrual disorders, but also for stroke. However, the neuroprotective role of DSS after ischemia-induced brain injury is still unknown. Therefore, the aim of our study was to determine the possible underlying mechanism for DSS’s neuroprotective effect after stroke. Based on current literature, we hypothesized that DSS reduces brain injury by promoting neurogenesis and angiogenesis via the VEGF/eNOS pathway. Adult female Sprague-Dawley rats were used for this study and randomly divided into three groups: sham, MCAO+Saline and MCAO+DSS. Transient middle cerebral artery occlusion (MCAO) was performed for 90 mins. The MCAO+DSS group was administered DSS (600 mg/kg/day) via the intragastric route at the time of reperfusion and once a day thereafter until the day before it was scheduled to be sacrificed. Neurobehavioral tests, immunohistochemistry, western blotting, and ELISA were performed 14 days after MCAO. We found that treatment with DSS indeed improved neurobehavioral outcomes remarkably. Furthermore, the number of BrdU+/DCX+ cells in the subventricular zone was significantly increased in DSS-treated rats compared with the saline-treated group. Similarly, the microvessel density in the perifocal region of DSS-treated rats was significantly higher vs. the saline-treated group. Lastly, DSS treatment was found to increase both VEGF expression and eNOS activation. Our study demonstrates for the first time that DSS promotes neurogenesis and focal angiogenesis through the VEGF/eNOS pathway, which attenuates ischemia-induced brain injury in rats; thus strongly suggesting that DSS is a potential treatment for ischemic stroke.

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HERBAL FORMULA DANGGUI-SHAOYAO-SAN PROMOTES NEUROGENESIS AND ANGIOGENESIS IN THE RAT FOLLOWING MIDDLE CEREBRAL ARTERY OCCLUSION

Studies show that the traditional Chinese medication, Danggui-Shaoyao-San (DSS), is not only beneficial for menstrual disorders, but also for stroke. However, the neuroprotective role of DSS after ischemia-induced brain injury is still unknown. Therefore, the aim of our study was to determine the possible underlying mechanism for DSS’s neuroprotective effect after stroke. Based on current literature, we hypothesized that DSS reduces brain injury by promoting neurogenesis and angiogenesis via the VEGF/eNOS pathway. Adult female Sprague-Dawley rats were used for this study and randomly divided into three groups: sham, MCAO+Saline and MCAO+DSS. Transient middle cerebral artery occlusion (MCAO) was performed for 90 mins. The MCAO+DSS group was administered DSS (600 mg/kg/day) via the intragastric route at the time of reperfusion and once a day thereafter until the day before it was scheduled to be sacrificed. Neurobehavioral tests, immunohistochemistry, western blotting, and ELISA were performed 14 days after MCAO. We found that treatment with DSS indeed improved neurobehavioral outcomes remarkably. Furthermore, the number of BrdU+/DCX+ cells in the subventricular zone was significantly increased in DSS-treated rats compared with the saline-treated group. Similarly, the microvessel density in the perifocal region of DSS-treated rats was significantly higher vs. the saline-treated group. Lastly, DSS treatment was found to increase both VEGF expression and eNOS activation. Our study demonstrates for the first time that DSS promotes neurogenesis and focal angiogenesis through the VEGF/eNOS pathway, which attenuates ischemia-induced brain injury in rats; thus strongly suggesting that DSS is a potential treatment for ischemic stroke.