B7 homolog 3 aggravates brain injury in a murine model of Streptococcus pneumoniae-induced meningitis.
B7 homolog 3 aggravates brain injury in a murine model of Streptococcus pneumoniae-induced meningitis.
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DOI：
10.3892/etm.2015.2333
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发表时间：
2015-05
影响因子：
2.7
通讯作者：
Xu-qin Chen;Yanping Wang;Zhe-dong Wang;R. Yan;Jie Liu;Xiangying Meng;Yan Li;Jianghuai Wang;Jian Wang
中科院分区：
文献类型：
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作者：
Xu-qin Chen;Yanping Wang;Zhe-dong Wang;R. Yan;Jie Liu;Xiangying Meng;Yan Li;Jianghuai Wang;Jian Wang
尽管使用了抗生素，但肺炎链球菌（SP）引起的脑膜炎仍然是一种危及生命的疾病，具有高致死率和严重神经系统后遗症的高风险，特别是在发展中国家。本研究探讨了共刺激分子B7同源物3 （B7- h3）在实验性sp致脑膜炎发病机制中的作用。小鼠脑室内注射血清3型SP（含或不含B7-H3）。通过体重下降和自发性运动活动（神经学评分）检查sp致脑膜炎小鼠的临床状况。对冠状脑切片进行nsll阳性神经元和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）阳性细胞计数。免疫组化染色检测脑组织神经元特异性烯醇化酶（NSE）和S100B蛋白的表达。所有实验均在随机盲法环境下进行。通过脑室注射SP悬浮液，成功地建立了小鼠肺炎球菌脑膜炎模型。在sp诱导的脑膜炎模型中，B7-H3恶化了临床状况，表现为神经学评分下降和体重减轻。B7-H3攻毒后，SP性脑膜炎小鼠脑组织中nissl阳性细胞数量减少，tunel染色阳性细胞数量增加，分别表明神经元坏死和细胞凋亡增强。NSE蛋白表达降低，S100B蛋白表达升高。这些体内研究结果表明，B7-H3在实验性sp性脑膜炎的病理过程中加重了脑损伤。
Despite the application of antibiotics, Streptococcus pneumoniae (SP)-induced meningitis continues to be a life-threatening disease with a high fatality rate and an elevated risk of serious neurological sequelae, particularly in developing countries. In this study, the contribution of the co-stimulatory molecule B7 homolog 3 (B7-H3) to the pathogenesis of experimental SP-induced meningitis was investigated. Mice were challenged with the intracerebroventricular injection of serotype 3 SP with or without B7-H3. The clinical status of mice with SP-induced meningitis was examined by body weight loss and spontaneous motor activity with neurological scoring. Coronal brain sections were analyzed by counting Nissl-positive neurons and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells. Protein expression of neuron-specific enolase (NSE) and S100B in brain tissues was examined with immunohistochemical staining. All experiments were performed in a randomized and blinded setting. By the intracerebroventricular injection of SP suspension, a murine model of pneumococcal meningitis was successfully established. In this SP-induced meningitis model, B7-H3 deteriorated the clinical status, as manifested by a decreased neurological score and increased body weight loss. Following the B7-H3 challenge, the number of Nissl-positive cells decreased and TUNEL-stained positive cells increased in the brain tissues of mice with SP meningitis, which demonstrates the enhancement of neuronal necrosis and apoptosis, respectively. Protein expression of NSE was decreased, while that of S100B was increased. These in vivo findings indicate that B7-H3 aggravates brain injury during the pathological process of experimental SP-induced meningitis.