Minocycline ameliorates cognitive impairment induced by whole-brain irradiation: an animal study

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• 作者：Liyuan Zhang (1) (2) (3)
  Kun Li (1) (2) (4)
  Rui Sun (1) (2)
  Yuan Zhang (1) (2)
  JianFeng Ji (1) (2)
  Peigeng Huang (5)
  Hongying Yang (3) (6)
  Ye Tian (1) (2) (3)
  
  1. Department of Radiotherapy and Oncology ; Second Affiliated Hospital ; Soochow University ; 1055 Sanxiang Road ; Suzhou ; Jiangsu Province ; 215004 ; PR China
  2. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases ; Second Affiliated Hospital ; Soochow University ; 1055 Sanxiang Road ; Suzhou ; Jiangsu Province ; 215004 ; PR China
  3. Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions ; Suzhou ; Jiangsu Province ; 215123 ; PR China
  4. Department of Medical Oncology ; Affiliated Hospital of Taishan Medical University ; Taian ; Shandong Province ; 271000 ; PR China
  5. Department of Radiation Oncology ; Massachusetts General Hospital ; Harvard Medical School ; 100 Blossom Street ; Boston ; MA ; 02114 ; USA
  6. School of Radiation Medicine and Protection ; Medical College of Soochow University/School for Radiological and Interdisciplinary Sciences (RAD-X) ; Soochow University ; 199 Renai Road ; Suzhou Industrial Park ; Suzhou ; Jiangsu Province ; 215123 ; PR China
  
• 关键词：Whole ; brain irradiation ; Cognitive deficit ; Minocycline ; Newborn neuron ; Apoptosis ; Neurogenesis
• 刊名：Radiation Oncology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：9
• 期：1
• 全文大小：3,140 KB
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• 刊物主题：Oncology; Radiotherapy;
• 出版者：BioMed Central
• ISSN：1748-717X

文摘

Background It has been long recognized that cranial irradiation used for the treatment of primary and metastatic brain tumor often causes neurological side-effects such as intellectual impairment, memory loss and dementia, especially in children patients. Our previous study has demonstrated that whole-brain irradiation (WBI) can cause cognitive decline in rats. Minocycline is an antibiotic that has shown neuroprotective properties in a variety of experimental models of neurological diseases. However, whether minocycline can ameliorate cognitive impairment induced by ionizing radiation (IR) has not been tested. Thus this study aimed to demonstrate the potential implication of minocycline in the treatment of WBI-induced cognitive deficits by using a rat model. Methods Sprague Dawley rats were cranial irradiated with electron beams delivered by a linear accelerator with a single dose of 20 Gy. Minocycline was administered via oral gavages directly into the stomach before and after irradiation. The open field test was used to assess the anxiety level of rats. The Morris water maze (MWM) was used to assess the spatial learning and memory of rats. The level of apoptosis in hippocampal neurons was measured using immunohistochemistry for caspase-3 and relative markers for mature neurons (NeuN) or for newborn neurons (Doublecortin (DCX)). Neurogenesis was determined by BrdU incorporation method. Results Neither WBI nor minocycline affected the locomotor activity and anxiety level of rats. However, compared with the sham-irradiated controls, WBI caused a significant loss of learning and memory manifest as longer latency to reach the hidden platform in the MWM task. Minocycline intervention significantly improved the memory retention of irradiated rats. Although minocycline did not rescue neurogenesis deficit caused by WBI 2 months post-IR, it did significantly decreased WBI-induced apoptosis in the DCX positive neurons, thereby resulting in less newborn neuron depletion 12 h after irradiation. Conclusions Minocycline significantly inhibits WBI-induced neuron apoptosis, leading to less newborn neurons loss shortly after irradiation. In the long run, minocycline improves the cognitive performance of rats post WBI. The results indicate a potential clinical implication of minocycline as an effective adjunct in radiotherapy for brain tumor patients.