Lippert-Gruener Marcela, Maegele Marc, Garbe Janika, Angelov Doychin N
Department of Neurosurgery, University of Cologne, Germany.
Exp Neurol. 2007 Jan;203(1):82-94. doi: 10.1016/j.expneurol.2006.07.025. Epub 2006 Sep 11.
Recently we showed that the combination between MEOS and EE applied to rats for 7-15 days after traumatic brain injury (TBI) was associated with reduced CNS lesion volume and enhanced reversal of neuromotor dysfunction. In a continuation of this work, we tested whether these effects persisted for longer post-operative periods, e.g. 30 days post-injury (dpi). Rats were subjected to lateral fluid percussion (LFP) or to sham injury. After LFP, one third of the animals (injured and sham) was placed under conditions of standard housing (SH), one third was kept in EE-only, and one third received EE+MEOS. Standardized composite neuroscore (NS) for neurological functions and computerized analysis of the vibrissal motor performance were used to assess post-traumatic neuromotor deficits. These were followed by evaluation of the cortical lesion volume (CLV) after immunostaining for neuron-specific enolase, caspase 3 active, and GFAP. Finally, the volume of cortical lesion containing regeneration-associated proteins (CLV-RAP) was determined in sections stained for GAP-43, MAP2, and neuronal class III beta-tubulin. We found (i) no differences in the vibrissal motor performance; (ii) EE+MEOS rats performed significantly better than SH rats in NS; (iii) EE-only and EE+MEOS animals, but not SH rats, showed better recovery at 30 dpi than at 15 dpi; (iv) no differences among all groups in CLV (larger than that at 15 dpi) and CLV-RAP, despite a clear tendency to reduction in the EE-only and EE+MEOS rats. We conclude that EE+MEOS retards, but cannot prevent the increase of lesion volume. This retardation is sufficient for a continuous restoration of neurological functions.
最近我们发现，在创伤性脑损伤（TBI）后7至15天对大鼠应用微粒体乙醇氧化系统（MEOS）和丰富环境（EE）的联合治疗，与中枢神经系统（CNS）损伤体积减小以及神经运动功能障碍的逆转增强有关。在这项工作的后续研究中，我们测试了这些效应在更长的术后时期（例如损伤后30天，dpi）是否仍然存在。将大鼠进行侧方流体冲击伤（LFP）或假手术损伤。LFP术后，三分之一的动物（损伤组和假手术组）置于标准饲养条件（SH）下，三分之一仅饲养在丰富环境中，三分之一接受丰富环境+微粒体乙醇氧化系统治疗。使用神经功能标准化综合神经评分（NS）和触须运动性能的计算机化分析来评估创伤后神经运动缺陷。随后，在对神经元特异性烯醇化酶、活化的半胱天冬酶3和胶质纤维酸性蛋白（GFAP）进行免疫染色后，评估皮质损伤体积（CLV）。最后，在对生长相关蛋白43（GAP-43）、微管相关蛋白2（MAP2）和神经元III类β-微管蛋白进行染色的切片中，测定含有再生相关蛋白的皮质损伤体积（CLV-RAP）。我们发现：（i）触须运动性能无差异；（ii）在NS方面，丰富环境+微粒体乙醇氧化系统组大鼠的表现明显优于标准饲养组大鼠；（iii）仅丰富环境组和丰富环境+微粒体乙醇氧化系统组动物，但不是标准饲养组大鼠，在30 dpi时比15 dpi时恢复得更好；（iv）尽管仅丰富环境组和丰富环境+微粒体乙醇氧化系统组大鼠有明显的体积减小趋势，但所有组在CLV（大于15 dpi时）和CLV-RAP方面无差异。我们得出结论，丰富环境+微粒体乙醇氧化系统可延缓，但不能阻止损伤体积的增加。这种延缓足以持续恢复神经功能。
