Kubeck Justin P, Merola Andrew, Mathur Sameer, Brkaric Mario, Majid Kamran, Shanti Nael, Caruso Steve, Yuan Sontang, Lowe Thomas, Dwyer Anthony, Haher Thomas, O'Brien Michael
University Hospital of Brooklyn/Downstate Medical Center, Brooklyn, NY 11215, USA.
Spine (Phila Pa 1976). 2006 Feb 1;31(3):257-61. doi: 10.1097/01.brs.0000197151.95849.7f.
Interventional study.
To analyze the histologic effects of high-dose human equivalent methylprednisolone on the pulmonary, cardiac, intestinal, renal, hepatic, and splenic tissues in a spinal cord injury rat model.
There are numerous investigations of various medical interventions for the treatment of acute spinal cord trauma. Currently, the only generally accepted medical intervention in an acute spinal cord trauma is the intravenous administration of high doses of methylprednisolone. Although it has been nearly 2 decades since the first National Acute Spinal Cord Injury Study investigated the role high-dose steroids might play in the treatment of acute spinal cord trauma, controversy still exists regarding the efficacy of this treatment. To our knowledge, no study has examined the role of high-dose methylprednisolone in organ systems other than the spinal cord in an acute spinal cord injury model at the histologic level. This study attempts to characterize end organ histologic response to human dose equivalent (HDE) intravenous methylprednisolone administration in a rodent model of acute spinal cord injury.
A total of 48 Sprague-Dawley rats were divided equally into control and experimental groups. Each group was subdivided into 6 sets of 4 animals each, according to intervals after injury. Groups 1-6 consisted of animals euthanized at 0, 4, 8, 16, 24, and 48 hours after spinal cord injury. Paraplegia after lower thoracic laminectomy was achieved using a standardized Allen weight drop technique. Within 1 hour of injury, experimental animals were treated with HDE methylprednisolone, infused for 23 hours continuously. Liver, kidney, lung, intestine, spleen, and heart were harvested at variable intervals after injury and prepared for histologic examination. These slides were analyzed with microscopic staining techniques and compared in a blinded manner by a qualified pathologist.
Of all the end organs analyzed, the spleens were most affected. Lymphocytic depletion was seen in as little as 4 hours after methylprednisolone infusion and continued until 48 hours. Pulmonary tissues variably showed interstitial congestion and eosinophilic alveolar collections. Intestinal mucosal tissues showed edema and autolyzed mucosa from 16 hours onwards. Cardiac, kidney, and hepatic tissue did not differ significantly from controls.
Histologically, HDE methylprednisolone caused significant splenic lymphocytic depletion changes in as little as 4 hours. This trend of end organ lymphocytopenia continued to progress until 48 hours. Pulmonary eosinophilic infiltrates were seen from 8 until 24 hours. Intestinal mucosal edema and necrosis were seen in samples at 16 hours throughout 48 hours. This study was designed to evaluate end organ changes seen in an animal model of an acute spinal cord injury treated with HDE methylprednisolone. Study animals were infused with HDE methylprednisolone given according to the National Acute Spinal Cord Injury Study II protocol. The kidney, lung, cardiac, intestinal, splenic, and hepatic tissues from the aforementioned animals were then sectioned and analyzed using histologic staining techniques by a qualified pathologist.
干预性研究。
分析大剂量等效于人用剂量的甲基强的松龙对脊髓损伤大鼠模型的肺、心脏、肠道、肾脏、肝脏和脾脏组织的组织学影响。
针对急性脊髓损伤的各种医学干预措施已有大量研究。目前，急性脊髓损伤中唯一普遍接受的医学干预是静脉注射大剂量甲基强的松龙。尽管自首个国家急性脊髓损伤研究调查大剂量类固醇在急性脊髓损伤治疗中可能发挥的作用以来已近20年，但对于这种治疗方法的疗效仍存在争议。据我们所知，在急性脊髓损伤模型中，尚未有研究在组织学水平上考察大剂量甲基强的松龙在脊髓以外的器官系统中的作用。本研究试图在急性脊髓损伤的啮齿动物模型中，描述终末器官对等效于人用剂量（HDE）静脉注射甲基强的松龙的组织学反应。
48只Sprague-Dawley大鼠平均分为对照组和实验组。根据损伤后的时间间隔，每组再分为6组，每组4只动物。第1 - 6组由脊髓损伤后0、4、8、16、24和48小时处死后的动物组成。通过标准化的Allen重物坠落技术在胸段下部椎板切除术后造成截瘫。在损伤后1小时内，对实验组动物给予HDE甲基强的松龙，持续输注23小时。在损伤后的不同时间间隔采集肝脏、肾脏、肺、肠道、脾脏和心脏，准备进行组织学检查。这些玻片采用显微染色技术进行分析，并由一名合格的病理学家以盲法进行比较。
在所有分析的终末器官中，脾脏受影响最大。甲基强的松龙输注后仅4小时就可见淋巴细胞耗竭，并持续至48小时。肺组织不同程度地显示间质充血和嗜酸性肺泡聚集。肠道黏膜组织从16小时起出现水肿和自溶的黏膜。心脏、肾脏和肝脏组织与对照组相比无显著差异。
组织学上，HDE甲基强的松龙在仅4小时内就引起脾脏淋巴细胞显著耗竭变化。这种终末器官淋巴细胞减少的趋势持续发展至48小时。在8至24小时可见肺部嗜酸性浸润。在16小时至48小时的样本中可见肠道黏膜水肿和坏死。本研究旨在评估在HDE甲基强的松龙治疗的急性脊髓损伤动物模型中观察到的终末器官变化。研究动物按照国家急性脊髓损伤研究II方案给予HDE甲基强的松龙。然后，由一名合格的病理学家使用组织学染色技术对上述动物的肾脏、肺、心脏、肠道、脾脏和肝脏组织进行切片分析。
