PMID- 29984620 OWN - NLM STAT- MEDLINE DCOM- 20190517 LR - 20211204 IS - 1555-3892 (Electronic) IS - 0963-6897 (Print) IS - 0963-6897 (Linking) VI - 27 IP - 4 DP - 2018 Apr TI - Enhanced Neurogenesis and Collaterogenesis by Sodium Danshensu Treatment After Focal Cerebral Ischemia in Mice. PG - 622-636 LID - 10.1177/0963689718771889 [doi] AB - Ischemic stroke remains a serious threat to human life. There are limited effective therapies for the treatment of stroke. We have previously demonstrated that angiogenesis and neurogenesis in the brain play an important role in functional recovery following ischemic stroke. Recent studies indicate that increased arteriogenesis and collateral circulation are determining factors for restoring reperfusion and outcomes of stroke patients. Danshensu, the Salvia miltiorrhiza root extract, is used in treatments of various human ischemic events in traditional Chinese medicine. Its therapeutic mechanism, however, is not well clarified. Due to its proposed effect on angiogenesis and arteriogenesis, we hypothesized that danshensu could benefit stroke recovery through stimulating neurogenesis and collaterogenesis in the post-ischemia brain. Focal ischemic stroke targeting the right sensorimotor cortex was induced in wild-type C57BL6 mice and transgenic mice expressing green fluorescent protein (GFP) to label smooth muscle cells of brain arteries. Sodium danshensu (SDS, 700 mg/kg) was administered intraperitoneally (i.p.) 10 min after stroke and once daily until animals were sacrificed. To label proliferating cells, 5-bromo-2'-deoxyuridine (BrdU; 50 mg/kg, i.p.) was administered, starting on day 3 after ischemia and continued once daily until sacrifice. At 14 days after stroke, SDS significantly increased the expression of vascular endothelial growth factor (VEGF), stromal-derived factor-1 (SDF-1), brain-derived neurotrophic factor (BDNF), and endothelial nitric oxide synthase (eNOS) in the peri-infarct region. SDS-treated animals showed increased number of doublecortin (DCX)-positive cells. Greater numbers of proliferating endothelial cells and smooth muscle cells were detected in SDS-treated mice 21 days after stroke in comparison with vehicle controls. The number of newly formed neurons labeled by NeuN and BrdU antibodies increased in SDS-treated mice 28 days after stroke. SDS significantly increased the newly formed arteries and the diameter of collateral arteries, leading to enhanced local cerebral blood flow recovery after stroke. These results suggest that systemic sodium danshensu treatment shows significant regenerative effects in the post-ischemic brain, which may benefit long-term functional recovery from ischemic stroke. FAU - Wei, Zheng Zachory AU - Wei ZZ AD - 1 Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. AD - 2 Experimental and Translational Research Center, Beijing Friendship Hospital, Beijing, China. AD - 3 Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA. FAU - Chen, Dongdong AU - Chen D AD - 3 Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA. FAU - Liu, Li-Ping AU - Liu LP AD - 4 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. FAU - Gu, Xiaohuan AU - Gu X AD - 3 Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA. FAU - Zhong, Weiwei AU - Zhong W AD - 3 Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA. FAU - Zhang, Yong-Bo AU - Zhang YB AD - 1 Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Wang, Yongjun AU - Wang Y AD - 4 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. FAU - Yu, Shan Ping AU - Yu SP AD - 3 Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA. FAU - Wei, Ling AU - Wei L AD - 1 Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. AD - 2 Experimental and Translational Research Center, Beijing Friendship Hospital, Beijing, China. AD - 3 Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA. AD - 5 Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA. LA - eng GR - R01 NS085568/NS/NINDS NIH HHS/United States GR - R01 NS091585/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Transplant JT - Cell transplantation JID - 9208854 RN - 0 (DCX protein, human) RN - 0 (Dcx protein, mouse) RN - 0 (Doublecortin Domain Proteins) RN - 0 (Doublecortin Protein) RN - 0 (Lactates) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Neuropeptides) RN - 4GF33A5PAJ (3,4-dihydroxyphenyllactic acid) SB - IM MH - Animals MH - Brain Ischemia/*drug therapy/pathology/*physiopathology MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Cerebrovascular Circulation/drug effects MH - Doublecortin Domain Proteins MH - Doublecortin Protein MH - Lactates/pharmacology/*therapeutic use MH - Male MH - Mice, Inbred C57BL MH - Microtubule-Associated Proteins/metabolism MH - Neovascularization, Physiologic/drug effects MH - Neural Stem Cells/drug effects/metabolism MH - Neurogenesis/*drug effects MH - Neuropeptides/metabolism MH - Recovery of Function/drug effects PMC - PMC7020234 OTO - NOTNLM OT - angiogenesis OT - arteriogenesis OT - cell migration OT - collaterogenesis OT - danshensu OT - ischemic stroke OT - neurogenesis COIS- Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2018/07/10 06:00 MHDA- 2019/05/18 06:00 PMCR- 2018/04/01 CRDT- 2018/07/10 06:00 PHST- 2018/07/10 06:00 [entrez] PHST- 2018/07/10 06:00 [pubmed] PHST- 2019/05/18 06:00 [medline] PHST- 2018/04/01 00:00 [pmc-release] AID - 10.1177_0963689718771889 [pii] AID - 10.1177/0963689718771889 [doi] PST - ppublish SO - Cell Transplant. 2018 Apr;27(4):622-636. doi: 10.1177/0963689718771889.