title: Tetramethylpyrazine enhances functional recovery after contusion spinal cord injury by modulation of MicroRNA-21, FasL, PDCD4 and PTEN expression.
abstract: Our previous study showed Tetramethylpyrazine (TMP) has protective effects against SCI. In this study, we aimed to uncover the mechanism underlying the protective effects of TMP in SCI. SCI was induced in Sprague-Dawley rats with a modified weight-drop device. One group was subjected to SCI in combination with TMP administration at a dose of 200mg/kgd, for 3 days. Concurrently, another group received SCI in combination with an equal volume of 0.9% saline. Locomotor functional recovery was assessed during the 4 weeks post-injury by performing the Basso, Beattie, and Bresnahan (BBB) rating procedure. Lesion size and spared tissue were measured by cresyl violet staining. MicroRNA-21 (miR-21) expression was determined by real-time PCR and in situ hybridization. FasL, PDCD4, and PTEN are direct targets of miR-21 in many diseases and cell types; their levels were analyzed by western blot. Immunohistochemistry was performed to observe the expression of PDCD4 and PTEN. Cell apoptosis was assessed by TUNEL staining and DNA laddering. TMP treatment after contusion SCI significantly improved functional recovery, decreased lesion size, and increased tissue sparing and miR-21 levels; expression of FasL, PDCD4, and PTEN was decreased. TMP treatment also reduced apoptosis after SCI. Thus, TMP administration improved functional recovery and reduced cell apoptosis. Its protective effect may partly based on increasing the expression of miR-21 and decreasing the expression of FasL, PDCD4, and PTEN. These could serve as new exploratory targets for SCI treatment.
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China; Department of orthopaedics, Fujian Provincial Hospital, 350001, PR China.
authors.forename: Jiang-Hu
authors.initials: JH
authors.lastname: Huang
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Sports Medicine, Research Center of Sports Medicine, Xiangya Hospital, Central South University, Changsha 410008, PR China. Electronic address: hongbinlu@hotmail.com.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Lu
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China. Electronic address: jianzhonghu@hotmail.com.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D003288:Contusions; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011719:Pyrazines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D051017:Apoptosis Regulatory Proteins; D053222:Fas Ligand Protein; D035683:MicroRNAs; D018696:Neuroprotective Agents; C467042:Pdcd4 protein, rat; D011719:Pyrazines; C546082:mirn21 microRNA, rat; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat; C017953:tetramethylpyrazine
keywords: Microrna-21; Spinal cord injury; Tetramethylpyrazine