Letechipía-Vallejo Graciela, López-Loeza Elisa, Espinoza-González Verónica, González-Burgos Ignacio, Olvera-Cortés María Esther, Moralí Gabriela, Cervantes Miguel
Facultad de Ciencias Médicas y Biológicas Dr. Ignacio Chávez, UMSNH, Morelia, Michoacán, Spain.
J Pineal Res. 2007 Mar;42(2):138-46. doi: 10.1111/j.1600-079X.2006.00395.x.
Consensus on neuroprotection has pointed out the relevance of the long-term morphological and functional evaluation of the effectiveness of putative neuroprotective procedures. In the present study, place learning (Morris water maze) and working memory (eight-arm Olton radial maze) were evaluated in adult male rats 90 days after 15 min of global cerebral ischemia (four-vessel occlusion) followed by continuous i.v. infusion (10 mg/kg/hr) of melatonin (Isch + Mel) or vehicle (Isch + Veh) for 6 hr, and the pyramidal neuron population of the cornus Ammoni (CA) of the hippocampus and layers III and V of the medial prefrontal cortex was assessed at the end of the behavioral testing period (120 days after ischemia). Impairment of place learning, a significant delay in working memory acquisition, and a significant loss of pyramidal neurons in the Ammon's horn (CA1: 23%, CA2: 52% CA3: 73%, hilus: 64% remaining neurons), were observed in the Isch + Veh group. By contrast, a similar performance of the Isch + Mel group to that in the Intact and Sham groups and better than that of the Isch + Veh group, besides a significant reduction of pyramidal neuron loss in the CA subfields (CA1: 79%, CA2: 88% CA3: 86%, hilus: 72% remaining neurons), documented that melatonin treatment led to a long-term preservation of both the neural substrate, and the capability for integration of spatial learning and memory, mainly dependent on a normal hippocampal functioning. Overall the results emphasize the efficacy of melatonin in counteracting the pathophysiological processes induced by ischemia, by exerting its actions during a short but critical period early after the ischemic episode.
神经保护方面的共识指出了对假定神经保护程序有效性进行长期形态学和功能评估的相关性。在本研究中，对成年雄性大鼠进行了位置学习（莫里斯水迷宫）和工作记忆（八臂奥尔顿放射状迷宫）评估。这些大鼠在经历15分钟全脑缺血（四动脉闭塞）后90天，随后连续静脉输注（10毫克/千克/小时）褪黑素（缺血+褪黑素组）或赋形剂（缺血+赋形剂组）6小时，并在行为测试期结束时（缺血后120天）评估海马齿状回（CA）的锥体细胞群以及内侧前额叶皮质的III层和V层。在缺血+赋形剂组中，观察到位置学习受损、工作记忆获取显著延迟以及海马角锥体细胞显著丢失（CA1：23%，CA2：52%，CA3：73%，齿状回：64%的剩余神经元）。相比之下，缺血+褪黑素组的表现与完整组和假手术组相似，且优于缺血+赋形剂组，此外CA亚区锥体细胞丢失显著减少（CA1：79%，CA2：88%，CA3：86%，齿状回：72%的剩余神经元），这证明褪黑素治疗可长期保留神经基质以及空间学习和记忆整合能力，这主要依赖于正常的海马功能。总体而言，结果强调了褪黑素在缺血发作后早期短暂但关键的时期发挥作用，从而对抗缺血诱导的病理生理过程的功效。
