Neuronal damage in rat brain and spinal cord after cardiac arrest and massive hemorrhagic shock
Neuronal damage in rat brain and spinal cord after cardiac arrest and massive hemorrhagic shock
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DOI：
10.1097/01.ccm.0000242522.48734.64
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发表时间：
2006-11-01
影响因子：
8.8
通讯作者：
Shioda, Seiji
中科院分区：
文献类型：
--
作者：
Kudo, Yoshifumi;Ohtaki, Hirokazu;Shioda, Seiji
目的：严重的全脑缺血常导致幸存者中枢神经系统的严重损害。后肢瘫痪是一种常见的缺陷所造成的全球性缺血。直到最近，大多数关于中枢神经系统全脑缺血的研究都是检查大脑或脊髓，而不是同时检查两者。尚未详细研究全脑缺血后的脊髓损伤。由于对脊髓神经元损伤的确切性质以及全脑缺血后脑和脊髓之间神经元损伤的差异知之甚少，我们开发了一种新的大鼠全脑缺血模型，并专门研究了全脑缺血后的脊髓损伤。此外，我们比较了不同形式的脑和脊髓全脑缺血后的神经元损伤。设计：随机，对照研究使用三种不同的全脑缺血模型在大鼠。实验对象：雄性成年Sprague-Dawley大鼠（300 g）。动物分为三个实验组，A组（n = 6，存活7天），失血性休克12分钟; B组（n = 6，存活7天），心脏停搏5分钟; C组（n = 6，分别为6小时，12小时，1天，3天和7天），失血性休克7分钟，心脏停搏5分钟。在复苏后6小时至7天研究后肢的运动缺陷。此外，未手术动物（n = 6）用作对照。采用电子显微镜对海马和腰髓CA 1区样本进行组织学分析（苏木精和伊红、Fluoro-Jade B、末端脱氧核苷酸转移酶介导的dUTP末端标记[TUNEL]、Kluver-Barrera）和超微结构分析。使用Scion Image软件半定量分析腰髓白色物质的脱髓鞘。在A组或B组中均未观察到截瘫动物。所有C组动物均表现出严重的后肢麻痹。各组大鼠海马CA 1区均出现严重的神经元损伤，迟发性神经元细胞死亡的情况在三组之间相似。仅在C组动物中检测到腰髓神经元损伤，主要在背角和中间灰质中。C组腹侧和腹外侧白色物质脱髓鞘明显。Scion Image软件显示对照组和C组大鼠之间存在显著差异。超微结构分析显示C组大鼠腰髓中中间灰质中广泛的坏死细胞死亡。出血性休克，随后心脏骤停）引起中枢神经系统中严重的神经元损伤。因此，全脑缺血后后肢瘫痪可能是脊髓损伤所致。这些结果表明，在治疗严重全脑缺血患者时，预防脊髓损伤的治疗策略是必要的。
Objective: Severe global ischemia often results in severe damage to the central nervous system of survivors. Hind-limb paralysis is a common deficit caused by global ischemia. Until recently, most studies of global ischemia of the central nervous system have examined either the brain or spinal cord, but not both. Spinal cord damage specifically after global ischemia has not been studied in detail. Because the exact nature of the neuronal damage to the spinal cord and the differences in neuronal damage between the brain and spinal cord after global ischemia are poorly understood, we developed a new global ischemia model in the rat and specifically studied spinal cord damage after global ischemia. Further, we compared the different forms of neuronal damage between the brain and spinal cord after global ischemia.Design: Randomized, controlled study using three different global ischemia models in the rat.Setting. University research laboratory.Subjects: Male, adult Sprague-Dawley rats (300 g).Interventions. Animals were divided into three experimental groups, group A (n = 6, survived for 7 days), 12 mins, of hemorrhagic shock; group B (n = 6, survived for 7 days), 5 mins of cardiac arrest; or group C (n = 6, each for 6 hrs, 12 hrs, 1 day, 3 days, and 7 days), 7 mins of hemorrhagic shock and 5 mins of cardiac arrest. Motor deficit of the hind limbs was studied 6 hrs to 7 days after resuscitation. Also, nonoperated animals (n = 6) were used as the control. Histologic analysis (hematoxylin and eosin, Fluoro-Jade B, terminal deoxynucleotidyl transferase-mediated dUTP end-labeling [TUNEL], Kluver-Barrera) and ultrastructural analysis using electron microscopy were performed on samples from the CA1 region of the hippocampus and lumbar spinal cord. Demyelination of the white matter of the lumbar spinal cord was analyzed semiquantitatively using Scion Image software.Main Results., No paraplegic animals were observed in either group A or B. All group C animals showed severe hind-limb paralysis. Severe neuronal damage was found in the CA1 region of the hippocampus in all groups, and the state of delayed neuronal cell death was similar among the three groups. Neuronal damage in the lumbar spinal cord was detected only in group C animals, mainly in the dorsal horn and intermediate gray matter. Demyelination was prominent in the ventral and ventrolateral white matter in group C. A significant difference was observed between control and group C rats with Scion Image software. Ultrastructural analysis revealed extensive necrotic cell death in the intermediate gray matter in the lumbar spinal cord in group C rats.Conclusion: The combination in the global ischemia model (i.e., hemorrhagic shock followed by cardiac arrest) caused severe neuronal damage in the central nervous system. Thereby, hind-limb paralysis after global ischemia might result from spinal cord damage. These results suggest that therapeutic strategies for preventing spinal cord injury are necessary when treating patents with severe global ischemia.