Coadministration of Ketamine and Perampanel Improves Behavioral Function and Reduces Inflammation in Acute Traumatic Brain Injury Mouse Model.
Coadministration of Ketamine and Perampanel Improves Behavioral Function and Reduces Inflammation in Acute Traumatic Brain Injury Mouse Model.
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DOI：
10.1155/2020/3193725
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发表时间：
2020
影响因子：
--
通讯作者：
Alamri FF
中科院分区：
文献类型：
--
作者：
Alqahtani F;Assiri MA;Mohany M;Imran I;Javaid S;Rasool MF;Shakeel W;Sivandzade F;Alanazi AZ;Al-Rejaie SS;Alshammari MA;Alasmari F;Alanazi MM;Alamri FF
创伤性脑损伤（TBI）是最令人衰弱的神经系统疾病之一，治疗选择不足。它影响全球所有年龄组，导致TBI后行为挑战和终身残疾，需要对这些健康问题进行干预。在本研究中，通过体重下降法对C57 BL/6 J小鼠进行TBI诱导，并观察了氯胺酮单独和与perampanel联合急性给药的结局。通过采用旷场测试（OFT）、Y-迷宫测试和新物体识别测试（NOR）来评估测试药物对TBI后行为变化的影响。之后，分析分离的血浆和脑匀浆中的炎症调节剂，即，通过ELISA检测NF-κB和iNOS。此外，还进行了代谢组学研究，以进一步验证药物的TBI拯救潜力。氯胺酮-perampanel联合给药的动物在OFT中表现出探索行为改善（P < 0.05），而氯胺酮单独给药以及联合给药在创伤后小鼠中产生了抗焦虑作用（P < 0.05 - 0.001）。同样，在Y-迷宫试验和NOR试验中，氯胺酮单独给药（P < 0.05）和氯胺酮-perampanel联合给药（P < 0.01 - 0.001）后，自发交替百分比和辨别指数百分比分别增加。ELISA证实氯胺酮-perampanel联合用药后，NF-κB（P < 0.05）和iNOS（P < 0.01 - 0.0001）的中枢和外周表达降低。如代谢组学研究所证明，通过药物组合恢复了TBI引起的血浆代谢物的改变。氯胺酮的结果是富有成效的，但联合治疗证明在改善所有研究参数方面更显着。这种新研究的复方制剂的益处可能是由于它们的抗组胺、抗氧化和神经保护能力。
Traumatic brain injury (TBI) is among the most debilitating neurological disorders with inadequate therapeutic options. It affects all age groups globally leading to post-TBI behavioral challenges and life-long disabilities requiring interventions for these health issues. In the current study, C57BL/6J mice were induced with TBI through the weight-drop method, and outcomes of acutely administered ketamine alone and in combination with perampanel were observed. The impact of test drugs was evaluated for post-TBI behavioral changes by employing the open field test (OFT), Y-maze test, and novel object recognition test (NOR). After that, isolated plasma and brain homogenates were analyzed for inflammatory modulators, i.e., NF-κB and iNOS, through ELISA. Moreover, metabolomic studies were carried out to further authenticate the TBI rescuing potential of drugs. The animals treated with ketamine-perampanel combination demonstrated improved exploratory behavior in OFT (P < 0.05), while ketamine alone as well as in combination yielded anxiolytic effect (P < 0.05‐0.001) in posttraumatic mice. Similarly, the % spontaneous alternation and % discrimination index were increased after the administration of ketamine alone (P < 0.05) and ketamine-perampanel combination (P < 0.01‐0.001) in the Y-maze test and NOR test, respectively. ELISA demonstrated the reduced central and peripheral expression of NF-κB (P < 0.05) and iNOS (P < 0.01‐0.0001) after ketamine-perampanel polypharmacy. The TBI-imparted alteration in plasma metabolites was restored by drug combination as evidenced by metabolomic studies. The outcomes were fruitful with ketamine, but the combination therapy proved more significant in improving all studied parameters. The benefits of this new investigated polypharmacy might be due to their antiglutamatergic, antioxidant, and neuroprotective capacity.
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通讯作者：
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