title: SDF-1α induces angiogenesis after traumatic brain injury.
abstract: This study aimed to investigate the effects of SDF-1α on brain angiogenesis and neurological functional recovery in rats after traumatic brain injury (TBI) and the potentially involved mechanisms. Youth male Wistar rats were injured via lateral fluid percussion injury and then randomly divided into one of 3 groups: I. vehicle treated group; II. SDF-1α neutralizing antibody treated group and III. rhSDF-1α treated group. rhSDF-1α and its neutralizing antibody or normal saline were administered to the brain penumbra via stereotactic injection 30min after TBI. Modified neurological severity score (mNSS) and Morris water maze (MWM) test were used to assess the neurologic functional recovery (n=6/group). 14days after injury, animals were euthanized and brain tissues were collected for quantitative real time polymerase chain reaction (qRT-PCR) (n=6/group) and immunohistochemistry (n=6/group) analysis. mNSS and MWM test indicated distinct amelioration of neurological disability in rhSDF-1α group(P<0.05). Microvessel density (MVD) of rhSDF-1α treated animals was remarkably increased around the injured area. On the contrary, MVD of the SDF-1α antibody administrated group was significantly decreased compared to that of vehicle treated animals (P<0.05). The mNSS and MVD had significant negative correlation as tested by Spearman rank correlation coefficient. Immunofluorescence staining showed that CD34 and CXCR4 co-expressed on microvessels. The rhSDF-1α treated animals had greater, contrarily, the SDF-1α antibody treated animals had lesser number of double positive microvessels compared to that of vehicle treated animals. The mRNA expression of CD34 and CXCR4 was obviously elevated in the rhSDF-1α administration group, conversely, declined in SDF-1α antibody treated animals around the injured area compared with that of the vehicle treatment group (P<0.05). These data indicated that SDF-1α could induce angiogenesis after TBI, potentially via SDF-1/CXCR4 axis.
authors.affiliation: Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, China. lishenghui2000@gmail.com
authors.forename: Shenghui
authors.initials: S
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Wei
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Zhou
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Xinliang
authors.initials: X
authors.lastname: Zhao
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D018952:Antigens, CD34 / Q000378:metabolism; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015599:Trauma Severity Indices
chemical_list: D043925:Angiogenesis Inducing Agents; D000906:Antibodies; D018952:Antigens, CD34; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D012333:RNA, Messenger; D019718:Receptors, CXCR4