title: Salidroside improves behavioral and histological outcomes and reduces apoptosis via PI3K/Akt signaling after experimental traumatic brain injury.
abstract: BACKGROUND
  Traumatic brain injury (TBI) induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K)/Akt signaling pathway.
  
  
  RESULTS
  Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg) or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC), and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro.
  
  
  CONCLUSIONS
  Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis following TBI, at least partially via the PI3K/Akt signaling pathway.
authors.affiliation: Departments of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, Republic of China. szufuchen@yahoo.com.tw
authors.forename: Szu-Fu
authors.initials: SF
authors.lastname: Chen
authors.forename: Hsin-Ju
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Tai-Ho
authors.initials: TH
authors.lastname: Hung
authors.forename: Chien-Cheng
authors.initials: CC
authors.lastname: Chen
authors.forename: Chao Yu
authors.initials: CY
authors.lastname: Lee
authors.forename: Chun-Hu
authors.initials: CH
authors.lastname: Wu
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Wang
authors.forename: Nien-Chieh
authors.initials: NC
authors.lastname: Liao
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000008:administration & dosage* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D008928:Mitochondria / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D009928:Organ Specificity; D010636:Phenols / Q000008:administration & dosage* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D045442:Rotarod Performance Test; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D000975:Antioxidants; D002867:Chromones; D005960:Glucosides; D009025:Morpholines; D018696:Neuroprotective Agents; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C009172:rhodioloside