Peterson D A, Lucidi-Phillipi C A, Eagle K L, Gage F H
Department of Neurosciences, University of California at San Diego, La Jolla 92093-0627.
J Neurosci. 1994 Nov;14(11 Pt 2):6872-85. doi: 10.1523/JNEUROSCI.14-11-06872.1994.
In vivo model systems that can evaluate neuronal death, survival, and regeneration are critical to revealing basic mechanisms of neuronal response and developing strategies for CNS repair. We propose a distinct experimental model of CNS degeneration following lesions to the perforant path connecting the hippocampus and the entorhinal cortex. Within 2 weeks of a unilateral aspirative perforant path lesion, 30% of the ipsilateral entorhinal cortex layer II (ECL II) projection neurons had died with no change in the contralateral ECL II population. Although there was no loss of ECL II neurons with normal aging, animals that survived for 15 months postlesion experienced an almost 50% loss of ipsilateral neurons compared to unlesioned controls. This progressive neuronal death was bilateral, with the contralateral ECL II experiencing a 30% decline in neuronal number relative to unlesioned controls. The use of unbiased stereology ensured that estimates of total number were not distorted by changes in the reference volume. The documented progressive neuronal death resulted in delayed behavioral impairment in spatial learning and performance (latency nearly 200% of controls). We propose, therefore, that the perforant path model is suitable for experimental investigation of neuronal survival and regeneration following CNS trauma.
能够评估神经元死亡、存活和再生的体内模型系统对于揭示神经元反应的基本机制以及制定中枢神经系统修复策略至关重要。我们提出了一种独特的实验模型，用于研究连接海马体和内嗅皮层的穿通通路损伤后中枢神经系统的退化情况。在单侧抽吸性穿通通路损伤后的2周内，同侧内嗅皮层第II层（ECL II）的投射神经元中有30%死亡，而对侧ECL II的神经元数量没有变化。虽然正常衰老过程中ECL II神经元不会丢失，但与未损伤的对照组相比，损伤后存活15个月的动物同侧神经元数量几乎减少了50%。这种进行性神经元死亡是双侧性的，与未损伤的对照组相比，对侧ECL II的神经元数量减少了30%。使用无偏倚的体视学方法确保了总数估计不会因参考体积的变化而失真。记录在案的进行性神经元死亡导致空间学习和表现方面的行为障碍延迟出现（潜伏期几乎是对照组的200%）。因此，我们认为穿通通路模型适用于中枢神经系统创伤后神经元存活和再生的实验研究。
