Programa de Bioquimica e Biofisica Celular, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
J Neurotrauma. 2010 May;27(5):829-41. doi: 10.1089/neu.2009.1189.
Preventing the harm caused by nerve degeneration is a major challenge in neurodegenerative diseases and in various forms of trauma to the nervous system. The aim of the current work was to investigate the effects of systemic administration of 2,4-dinitrophenol (DNP), a compound with newly recognized neuroprotective properties, on sciatic-nerve degeneration following a crush injury. Sciatic-nerve injury was induced by unilateral application of an aneurysm clip. Four groups of mice were used: uninjured, injured treated with vehicle (PBS), injured treated with two intraperitoneal doses of DNP (0.06 mg DNP/kg every 24 h), and injured treated with four doses of DNP (every 12 h). Animals were sacrificed 48 h post injury and both injured and uninjured (contralateral) sciatic nerves were processed for light and electron microscopy. Morphometric, ultrastructural, and immunohistochemical analysis of injured nerves established that DNP prevented axonal degeneration, blocked cytoskeletal disintegration, and preserved the immunoreactivity of amyloid precursor protein (APP) and Neuregulin 1 (Nrg1), proteins implicated in neuronal survival and myelination. Functional tests revealed preservation of limb function following injury in DNP-treated animals. Results indicate that DNP prevents nerve degeneration and suggest that it may be a useful small-molecule adjuvant in the development of novel therapeutic approaches in nerve injury.
预防神经退行性病变所造成的损伤是神经退行性疾病和各种形式的神经系统创伤的主要挑战。本研究旨在探讨全身性给予 2,4-二硝基苯酚（DNP）对夹伤引起的坐骨神经退行性病变的影响。DNP 是一种具有新的神经保护特性的化合物。坐骨神经损伤通过单侧应用动脉瘤夹来诱导。使用了四组小鼠：未损伤组、损伤后给予载体（PBS）处理组、损伤后给予两次腹腔内 DNP 处理组（每 24 小时 0.06 毫克 DNP/kg）和损伤后给予四次 DNP 处理组（每 12 小时一次）。动物在损伤后 48 小时被处死，损伤和未损伤（对侧）坐骨神经进行光镜和电镜检查。损伤神经的形态计量学、超微结构和免疫组织化学分析表明，DNP 可预防轴突变性、阻止细胞骨架解体，并保留淀粉样前体蛋白（APP）和神经调节蛋白 1（Nrg1）的免疫反应性，这些蛋白与神经元存活和髓鞘形成有关。功能测试显示，DNP 处理动物的肢体功能在损伤后得到了保留。结果表明 DNP 可预防神经退行性病变，并提示它可能是神经损伤新治疗方法开发的有用的小分子佐剂。
