Yu Chen-Guang, Geddes James W
Spinal Cord and Brain Injury Research Center and Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536-0509, USA.
Neurochem Res. 2007 Dec;32(12):2046-53. doi: 10.1007/s11064-007-9347-4. Epub 2007 May 3.
Following contusive spinal cord injury (SCI), calpain activity is dramatically increased and remains elevated for days to weeks. Although calpain inhibition has previously been demonstrated to be neuroprotective following spinal cord injury, most studies administered the calpain inhibitor at a single time point. We hypothesized that sustained calpain inhibition would improve functional and pathological outcomes, as compared to the results obtained with a single postinjury administration of the calpain inhibitor. Contusion SCI was produced in female Long-Evans rats using the Infinite Horizon spinal cord injury impactor at the 200 kdyn force setting. Open-field locomotor function was evaluated until 6 weeks postinjury. Histological assessment of lesion volume and tissue sparing was performed at 6 weeks after SCI. Calpain inhibitor MDL28170 administered as a single postinjury i.v. bolus (20 mg/kg) or as a daily i.p. dose (1 mg/kg) improved locomotor function, but did not increase tissue sparing. Combined i.v. and daily i.p. MDL28170 administration resulted in significant improvement in both functional and pathological outcome measures, supporting the calpain theory of SCI proposed by Dr. Banik and colleagues.
在脊髓挫伤性损伤（SCI）后，钙蛋白酶活性显著增加，并在数天至数周内持续升高。尽管先前已证明钙蛋白酶抑制在脊髓损伤后具有神经保护作用，但大多数研究仅在单一时间点给予钙蛋白酶抑制剂。我们推测，与损伤后单次给予钙蛋白酶抑制剂的结果相比，持续抑制钙蛋白酶将改善功能和病理结局。使用无限视野脊髓损伤撞击器在200千达因力设置下对雌性Long-Evans大鼠造成挫伤性SCI。在损伤后6周内评估旷场运动功能。在SCI后6周对损伤体积和组织保留情况进行组织学评估。损伤后单次静脉推注（20 mg/kg）或每日腹腔注射剂量（1 mg/kg）的钙蛋白酶抑制剂MDL28170可改善运动功能，但未增加组织保留。静脉注射和每日腹腔注射联合使用MDL28170可显著改善功能和病理结局指标，支持Banik博士及其同事提出的SCI钙蛋白酶理论。
