Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats.
Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats.
复制标题
DOI：
10.1089/neu.2015.4229
复制
发表时间：
2016-11-15
影响因子：
4.2
通讯作者：
Chiang YH
中科院分区：
文献类型：
--
作者：
Yu YW;Hsieh TH;Chen KY;Wu JC;Hoffer BJ;Greig NH;Li Y;Lai JH;Chang CF;Lin JW;Chen YH;Yang LY;Chiang YH
轻度创伤性脑损伤（mTBI）是一个主要的公共卫生问题，占所有TBI病例的75-90%。在临床环境中，mTBI（定义为13-15的昏迷量表（GCS）评分）可导致各种身体，认知，情绪和心理相关症状。迄今为止，没有基于药物的疗法来管理与mTBI相关的病理缺陷的发展。在这项研究中，葡萄糖依赖性促胰岛素多肽（GIP），一种类似于胰高血糖素样肽-1（GLP-1）的肠促胰岛素，在稳态皮下给药后研究了其神经营养和神经保护特性，重点关注体内动物模型中mTBI后的行为。mTBI大鼠模型通过轻度受控皮质撞击（mCCI）产生，并用于评估GIP的治疗潜力。我们使用Morris水迷宫和新物体识别测试，这是空间和识别记忆的任务，分别确定GIP对认知功能的假定治疗作用。此外，横梁行走和粘合剂去除试验用于评估mCCI损伤后给予和不给予GIP的大鼠的自发活动和躯体感觉功能。最后，我们使用免疫组织化学（IHC）染色和Western印迹分析来评估mTBI动物中的炎症标志物、胶质细胞酸性蛋白（GFAP）、淀粉样蛋白-β前体蛋白（APP）和X染色体中的骨髓酪氨酸激酶基因（BMX）。GIP耐受性良好，并改善mTBI诱导的记忆障碍，平衡差，感觉运动缺陷后，在损伤后阶段开始。此外，GIP减轻mTBI诱导的GFAP、APP和BMX蛋白水平的神经炎症变化。这些研究结果表明，GIP在管理mTBI相关症状方面具有显着益处，并代表了mTBI治疗的新策略。
Mild traumatic brain injury (mTBI) is a major public health issue, representing 75–90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13–15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.
登录
查看更多内容
影响因子：
4.7
作者：
Cerecedo-Lopez, Christian D.;Kim-Lee, Jennifer H.;Hernandez, Diana;Acosta, Sandra A.;Borlongan, Cesar V.
通讯作者：
Borlongan, Cesar V.
影响因子：
4.2
作者：
Dixon, CE;Kochanek, PM;DeKosky, ST
通讯作者：
DeKosky, ST
影响因子：
4.1
作者：
DIXON, CE;LYETH, BG;HAYES, RL
通讯作者：
HAYES, RL
影响因子：
2.7
作者：
BARTH, TM;JONES, TA;SCHALLERT, T
通讯作者：
SCHALLERT, T
影响因子：
3
作者：
Ding, Ke-Hong;Zhong, Qing;Isales, Carlos M.
通讯作者：
Isales, Carlos M.