Málková L, Lex C K, Mishkin M, Saunders R C
Department of Pharmacology, Georgetown University Medical Center, Washington, DC, USA.
Hippocampus. 2001;11(4):361-70. doi: 10.1002/hipo.1050.
To minimize the variability in the extent of lesions made by injections of the excitotoxin ibotenic acid in rhesus monkeys, we developed and validated an MRI-based method to determine the efficacy of the injections soon after surgery. T2-weighted MR images were obtained 6-11 days after surgery from 17 brain hemispheres of monkeys that had received bilateral lesions of either the hippocampal formation (HF), perirhinal cortex, or parahippocampal cortex. The extent of lesion estimated from the hypersignal that appeared in and outside of the targeted area on these MR images was compared with the extent of damage assessed histologically after survival periods ranging from 120-370 days. Highly significant correlations (r values between 0.85-0.99) were found between these two measures for several regions in the medial temporal lobe. Based on this finding, lack of hypersignal in the targeted area of some Ss was followed by successful reinjection of the neurotoxin to create more complete cell loss prior to the postoperative phase of the study. We also assessed the relationship between a postoperative reduction in HF volume, measured from T1-weighted MR images, and the extent of damage determined histologically in 14 hemispheres of monkeys with bilateral excitotoxic HF lesions. The HF volume decreases sharply after surgery until 40-50 days postoperatively, after which there is only a minor further decrease. Based on this finding, we obtained T1-weighted MR images at least 44 days but in most cases close to 1 year after surgery. A highly significant positive correlation (r = 0.95, P < 0.001) was found between neuronal damage and volume reduction, with nearly complete neuronal damage (96-99%) corresponding to a volume reduction of 68-79%. These MRI-based methods thus provide an accurate in vivo evaluation of the locus and extent of neurotoxic lesions. Application of these methods can ensure that each animal in the experiment is used effectively.
为了使恒河猴注射兴奋性毒素鹅膏蕈氨酸所造成的损伤范围的变异性最小化，我们开发并验证了一种基于磁共振成像（MRI）的方法，用于在手术后不久确定注射的效果。在接受海马结构（HF）、嗅周皮质或海马旁皮质双侧损伤的猴子的17个脑半球中，于术后6 - 11天获取T2加权磁共振图像。将这些磁共振图像上目标区域内外出现的高信号所估计的损伤范围，与在120 - 370天的存活期后组织学评估的损伤范围进行比较。在内侧颞叶的几个区域，这两种测量方法之间发现了高度显著的相关性（r值在0.85 - 0.99之间）。基于这一发现，对于一些实验对象，若其目标区域缺乏高信号，则在研究的术后阶段之前成功再次注射神经毒素，以造成更完全的细胞损失。我们还评估了从T1加权磁共振图像测量的术后HF体积减少与在14个患有双侧兴奋性毒性HF损伤的猴子脑半球中组织学确定的损伤程度之间的关系。手术后HF体积急剧下降，直到术后40 - 50天，此后只有轻微的进一步下降。基于这一发现，我们在手术后至少44天但在大多数情况下接近1年时获取T加权磁共振图像。在神经元损伤和体积减少之间发现了高度显著的正相关（r = 0.95，P < 0.001），几乎完全的神经元损伤（96 - 99%）对应着68 - 79%的体积减少。因此，这些基于MRI的方法提供了对神经毒性损伤的部位和范围的准确体内评估。应用这些方法可以确保实验中的每只动物都得到有效利用。
