SDF-1α induces angiogenesis after traumatic brain injury

This study aimed to investigate the effects of SDF-1 alpha on brain angiogenesis and neurological functional recovery in rats after traumatic brain injury (TB!) 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-1 alpha neutralizing antibody treated group and III. rhSDF-1 alpha treated group. rhSDF-1 alpha and its neutralizing antibody or normal saline were administered to the brain penumbra via stereotactic injection 30 min after TBI. Modified neurological severity score (mNSS) and Morris water maze (MWM) test were used to assess the neurologic functional recovery (n=6/group). 14 days 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-1 alpha group(P<0.05). Microvessel density (MVD) of rhSDF-1 alpha treated animals was remarkably increased around the injured area. On the contrary, MVD of the SDF-1 alpha 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-1 alpha treated animals had greater, contrarily, the SDF-1 alpha 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-1 alpha administration group, conversely, declined in SDF-1 alpha antibody treated animals around the injured area compared with that of the vehicle treatment group (P<0.05). These data indicated that SDF-1 alpha could induce angiogenesis after TB!, potentially via SDF-1/CXCR4 axis. (C) 2012 Elsevier B.V. All rights reserved.