Ravikumar R, Fugaccia Isabella, Scheff Stephen W, Geddes James W, Srinivasan Cidambi, Toborek Michal
Department of Surgery, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
J Neurotrauma. 2005 Feb;22(2):240-51. doi: 10.1089/neu.2005.22.240.
Protection against the progression of secondary injury appears to be an effective therapeutic strategy in spinal cord injury (SCI). Evidence indicates that nicotine can induce potent neuroprotective effects against injury to spinal cord neurons. Therefore, the present study was focused on the effects of nicotine on the behavioral and morphological recovery associated with SCI. Adult male Long-Evans rats were subjected to a moderate contusion model of SCI and received subcutaneous injections of nicotine for 14 days at the dose of 0.35 or 7 mg/kg/day. The rats were examined using the BBB locomotor rating scale for 6 weeks. At the end of the BBB recording, spinal cords were examined for the volumetric tissue sparing of gray and white matters. All SCI rats demonstrated a loss of hindlimb function followed by a recovery phase that peaked at 2-3 weeks after the trauma. Compared to untreated SCI rats, chronic nicotine administration appeared to improve the recovery of the locomotor functions. Indeed, nicotine-treated animals scored consistently higher on the BBB scale indicating that the treatment altered animal behavior. However, when taking under consideration correction factors for multiple comparisons, these data did not reach significance at overall experimental levels of significance 0.05. Nevertheless, nicotine administration was effective in sparing tissue at injury epicenter and a lower dose of nicotine also resulted in significant sparing of white matter of the injured spinal cord. These results suggest that agonists of neuronal nicotinic receptors can be attractive candidates for SCI therapy.
预防继发性损伤的进展似乎是脊髓损伤（SCI）的一种有效治疗策略。有证据表明，尼古丁可对脊髓神经元损伤产生强大的神经保护作用。因此，本研究聚焦于尼古丁对与SCI相关的行为和形态恢复的影响。成年雄性Long-Evans大鼠接受中度SCI挫伤模型，并以0.35或7mg/kg/天的剂量皮下注射尼古丁14天。使用BBB运动评分量表对大鼠进行6周的检查。在BBB记录结束时，检查脊髓灰质和白质的体积性组织保留情况。所有SCI大鼠均出现后肢功能丧失，随后进入恢复阶段，在创伤后2-3周达到峰值。与未治疗的SCI大鼠相比，长期给予尼古丁似乎可改善运动功能的恢复。实际上，接受尼古丁治疗的动物在BBB量表上的得分始终较高，表明该治疗改变了动物行为。然而，在考虑多重比较的校正因素时，这些数据在总体实验显著性水平0.05时未达到显著性。尽管如此，给予尼古丁可有效保留损伤中心的组织，较低剂量的尼古丁也可显著保留受损脊髓的白质。这些结果表明，神经元烟碱受体激动剂可能是SCI治疗的有吸引力的候选药物。
