Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat

被引:224
作者
Lee, SM
Yune, TY
Kim, SJ
Park, DW
Lee, YK
Kim, YC
Oh, YJ
Markelonis, GJ
Oh, TH
机构
[1] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA
[2] Seoul Natl Univ, Coll Pharm, Seoul, South Korea
[3] Korea Inst Sci & Technol, Biomed Res Ctr, Seoul 130650, South Korea
[4] Yonsei Univ, Dept Biol, Seoul 120749, South Korea
关键词
apoptosis; BBB score; caspase-3; DNA laddering; functional recovery; IL-10; inflammation; lesion area; minocycline; spinal cord injury; TUNEL;
D O I
10.1089/089771503770195867
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
We examined the effects of minocycline, an anti-inflammatory drug, on functional recovery following spinal cord injury (SCI). Rats received a mild, weight-drop contusion injury to the spinal cord and were treated with the vehicle or minocycline at a dose of 90 mg/kg immediately after SCI and then twice at a dose of 45 mg/kg every 12 h. Injecting minocycline after SCI improved hind limb motor function as determined by the Basso-Beattie-Bresnahan (BBB) locomotor open field behavioral rating test. Twenty four to 38 days after SCI, BBB scores were significantly higher in minocycline-treated rats as compared with those in vehicle-treated rats. Morphological analysis showed that lesion size increased progressively in both vehicle-treated and minocycline-treated spinal cords. However, in response to treatment with minocycline, the lesion size was significantly reduced at 21-38 days after SCI when compared to the vehicle control. Minocycline treatment significantly reduced the number of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive cells 24 h after SCI as compared to that of the vehicle control. DNA gel electrophoresis also revealed a marked decrease in DNA laddering in response to treatment with minocycline. In addition, minocycline treatment significantly reduced the specific caspase-3 activity after SCI as compared to that of vehicle control. Furthermore, RT-PCR analyses revealed that minocycline treatment increased expression of interleukin-10 mRNA but decreased tumor necrosis factor-alpha expression. These data suggest that, after SCI, minocycline treatment modulated expression of cytokines, attenuated cell death and the size of lesions, and improved functional recovery in the injured rat. This approach may provide a therapeutic intervention enabling us to reduce cell death and improve functional recovery after SCI.
引用
收藏
页码:1017 / 1027
页数:11
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