MP1-12 A MURINE MODEL OF SPINAL CORD INJURY: EFFECT OF THE GENERAL MATRIX METALLOPROTEINASE INHIBITOR GM6001 ON LONG-TERM LOCOMOTOR AND BLADDER FUNCTION
Thomas M. FandelAlpa TrivediAida F. MartinezHaoqian ZhangJonathan M. LevineLinda J. Noble‐Haeusslein
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You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 2014MP1-12 A MURINE MODEL OF SPINAL CORD INJURY: EFFECT OF THE GENERAL MATRIX METALLOPROTEINASE INHIBITOR GM6001 ON LONG-TERM LOCOMOTOR AND BLADDER FUNCTION Thomas M. Fandel, Alpa Trivedi, Aida F. Martinez, Haoqian Zhang, Jonathan M. Levine, and Linda J. Noble-Haeusslein Thomas M. FandelThomas M. Fandel More articles by this author , Alpa TrivediAlpa Trivedi More articles by this author , Aida F. MartinezAida F. Martinez More articles by this author , Haoqian ZhangHaoqian Zhang More articles by this author , Jonathan M. LevineJonathan M. Levine More articles by this author , and Linda J. Noble-HaeussleinLinda J. Noble-Haeusslein More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.110AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We have previously shown that GM6001 improves locomotor function in a murine model of moderate spinal cord contusion injury (SCI), when treatment is initiated at 3 hours post-injury. Here we determine efficacy of GM6001 on locomotor and bladder function after two levels of SCI and when the initial treatment is delayed to 8 hours post-injury. METHODS Adult, male, C57Bl/6 mice were subjected to moderate-severe (n=23) or severe (n=24) SCI, produced by dropping either a 2g or 3g weight respectively onto the exposed spinal cord at the T9 vertebral level. Injured mice were randomized to receive drug (GM6001 at 100mg/kg, n=11/12) or vehicle (99% DMSO, s.c. n=12/12) starting 8 hours after injury and then twice daily for 3 consecutive days. Nine animals served as uninjured controls. Neurological status was evaluated at 1 and 3 days post-injury and weekly thereafter for 5 weeks using the Basso Mouse Scale (BMS). At 5-6 weeks, a PE10 catheter was implanted into the bladder dome and conscious cystometry was performed 2-3 days later. Two-way repeated measures analysis of variance and unpaired T-Tests were used to evaluate locomotor recovery and bladder function, respectively. Significance was defined as p<0.05. RESULTS On BMS score in the moderate-severe injury group, there was an effect of both time (p<0.0001) and treatment (p=0.04). In contrast, in the severe injury group, there was an effect of time (p<0.0001) but not of treatment on locomotor recovery (p=0.8). Cystometry after moderate-severe injury revealed a therapeutic effect of GM6001 on the number of uninhibited bladder contractions (UBC)/ voiding cycle (p=0.007), time to first void (p=0.0004), residual urine (p=0.004), and voiding efficacy (p=0.008). GM6001 treatment in the severe injury group reduced the number of UBC/ voiding cycle compared to its injury control (p=0.03). CONCLUSIONS Here we provide the first evidence that GM6001 improves both locomotor and bladder function when treatment is delayed to a more clinically relevant time point of 8 hours post-injury and after a moderate severe spinal cord injury. Such findings support the candidacy of this drug for clinical trials. Changes in bladder function following spinal cord injury Uninjured Controls Moderate-severe SCI Controls Moderate-severe SCI GM6001 Severe SCI Controls Severe SCI GM6001 Uninhibited bladder contractions/ voiding cycle 1.7 ± 0.6 17.2 ± 2.7 8.4 ± 1.4** 10.6 ± 2.0 4.9 ± 1.2* Time to first void (min) 12.4 ± 2.0 45.9 ± 4.5 19.7 ± 4.0*** 30.1 ± 6.9 29.5 ± 4.4 Residual urine (ml) 0.007 ± 0.004 0.648 ± 0.047 0.249 ± 0.087** 0.463 ± 0.088 0.403 ± 0.073 Voiding efficacy (%) 93.1 ± 3.7 0.2 ± 0.1 35.5 ± 10.7** 18.6 ± 8.6 20.9 ± 11.4 * p < 0.05, ** p < 0.01, *** p < 0.001 vs. respective injury controls © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e5-e6 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Thomas M. Fandel More articles by this author Alpa Trivedi More articles by this author Aida F. Martinez More articles by this author Haoqian Zhang More articles by this author Jonathan M. Levine More articles by this author Linda J. Noble-Haeusslein More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...Cite
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Seperti pada dewasa, teknik regional anestesi pada pediatrik kini makin popular digunakan oleh ahli anestesikarena keuntungannya. Namun demikian selalu ada risiko dan kemungkinan timbulnya komplikasi dari setiap tindakan yang dilakukan, termasuk tindakan anestesi regional pada pediatrik. Insidensi komplikasi anestesi regional pada pediatrik tidak banyak, dan kalaupun terjadi komplikasi adalah minor. Komplikasi bisa diakibatkan dari identifikasi ruang saraf, alat, obat, teknis tindakan anestesi regionalnya dan komplikasi lainnya.Walaupun tidak banyak kejadian komplikasi regional anestesi yang dilaporkan pada pediatrik, dan bukanlah komplikasi yang fatal, teknik regional anestesi pada pediatrik harus dilakukan dengan lebih hatihati, pertimbangan risiko dan keuntungannya untuk menghindari terjadinya komplikasi, terlebih karena kebanyakan komplikasi dapat dihindari dengan mempelajari teknik yang benar, menggunakan peralatan yang sesuai, dan sangat menerapkan prinsip keamanan pada pasien dengan baik.
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Genentech is partnering with the German cancer company Affimed to develop immunotherapies for multiple kinds of solid and blood cancers. Affimed is developing therapies that engage natural killer cells of the innate immune system to help direct them to attack cancer cells. Genentech will pay Affimed $96 million up front and up to $5 billion more in potential payments.
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Objective:Investigate the mechanism of blood spinal cord barrier disruption after spinal cord injury.Method:Thirty five male adult Wistar rats(300～350g) were randomly assigned to this study,there were one control group and six spinal cord injury groups(acording to the time of post injury,4h,6h,12h,24h,48h and 72h).Each group contained 5 rats and New York University (NYU) Spinal Cord Injury Model was utilized to create the spinal cord injury.The immunoexpressior changes of immunglobularprotein G(IgG),c fragment of complement3 (C3c) in different time after spinal cord injury were evaluated utilizing immunohistochemistry method.Result:After spinal cord injury, there was a marked chang in the immunoexpressior of IgG and C3c in the impact site, near the impact site and spinal cord microvascular.Conclusion:After spinal cord injury,IgG and C3c may be important factors of barrier disruption and related to neuron secondary injury.
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Objective To investigate the expression changes of CD44 in spinal cord in 3d,7d and 14d following hemisection of spinal cord injury(hSCI).Furthermore,to explore the relationships of CD44 and spinal cord injury.Besides,to offer the morphological datum for the research concerning the spinal cord repair.Methods 20 adult healthy Sprague-Dawley rats were randomly divided into sham-operated control group and day3,day7,day14 spinal cord injury groups.The spinal cords were hemisected between T9 and T10.The spinal cord of every rat was taken out from the rostral and caudal segments of lesioned areas.Then the tissue blocks were made into 25μm frozen sections and the immunohistochemistry ABC method was performed on these sections.We respectively observe and count the number of CD44 positive cells in spinal cord for all groups,and the average OD(optical density) value of immunoreactant were detected with computer image analysis technique.Results CD44 positive products were mainly distributed in extacellular matrix and neurons and neuroglial cells in spinal cord for the control group.The number of CD44 positive cells and its OD value of rostral or caudal part of injury site for the three spinal cord injury groups were all increased(P0.05).Conclusion The increased-expression CD44 may mutually play inhibitory effect on axon regeneration following SCI.
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