Castro Lidia, Noelia Montoya, Vidal-Jorge Marian, Sánchez-Ortiz David, Gándara Darío, Martínez-Saez Elena, Cicuéndez Marta, Poca Maria-Antonia, Simard J Marc, Sahuquillo Juan
Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Department of Neurosurgery, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
J Neurotrauma. 2019 Jan 1;36(1):165-175. doi: 10.1089/neu.2017.5619. Epub 2018 Jul 24.
Brain contusions (BCs) are one of the most frequent lesions in patients with moderate and severe traumatic brain injury (TBI). BCs increase their volume due to peri-lesional edema formation and/or hemorrhagic transformation. This may have deleterious consequences and its mechanisms are still poorly understood. We previously identified upregulation sulfonylurea receptor (SUR) 1, the regulatory subunit of adenosine triphosphate (ATP)-sensitive potassium (K) channels and other channels, in human BCs. Our aim here was to study the expression of the pore-forming subunit of K, Kir6.2, in human BCs, and identify its localization in different cell types. Protein levels of Kir6.2 were detected by western blot (WB) from 33 contusion specimens obtained from 32 TBI patients aged 14-74 years. The evaluation of Kir6.2 expression in different cell types was performed by immunofluorescence in 29 contusion samples obtained from 28 patients with a median age of 42 years. Control samples were obtained from limited brain resections performed to access extra-axial skull base tumors or intraventricular lesions. Contusion specimens showed an increase of Kir6.2 expression in comparison with controls. Regarding cellular location of Kir6.2, there was no expression of this channel subunit in blood vessels, either in control samples or in contusions. The expression of Kir6.2 in neurons and microglia was also analyzed, but the observed differences were not statistically significant. However, a significant increase of Kir6.2 was found in glial fibrillary acidic protein (GFAP)-positive cells in contusion specimens. Our data suggest that further research on SUR1-regulated ionic channels may lead to a better understanding of key mechanisms involved in the pathogenesis of BCs, and may identify novel targeted therapeutic strategies.
脑挫伤(BCs)是中重度创伤性脑损伤(TBI)患者中最常见的损伤之一。由于损伤周围水肿形成和/或出血性转化,脑挫伤体积会增大。这可能会产生有害后果,但其机制仍知之甚少。我们之前在人类脑挫伤中发现磺脲类受体(SUR)1上调,SUR1是三磷酸腺苷(ATP)敏感性钾(K)通道及其他通道的调节亚基。我们在此的目的是研究K通道的孔形成亚基Kir6.2在人类脑挫伤中的表达,并确定其在不同细胞类型中的定位。通过蛋白质印迹法(WB)检测了33例脑挫伤标本中Kir6.2的蛋白水平,这些标本取自32例年龄在14至74岁的TBI患者。通过免疫荧光法对29例脑挫伤样本中Kir6.2在不同细胞类型中的表达进行了评估,这些样本取自28例年龄中位数为42岁的患者。对照样本取自为切除轴外颅底肿瘤或脑室内病变而进行的有限脑切除术。与对照相比,脑挫伤标本中Kir6.2的表达增加。关于Kir6.2的细胞定位,无论是在对照样本还是脑挫伤样本中,该通道亚基在血管中均无表达。我们还分析了Kir6.2在神经元和小胶质细胞中的表达,但观察到的差异无统计学意义。然而,在脑挫伤标本中,在胶质纤维酸性蛋白(GFAP)阳性细胞中发现Kir6.2显著增加。我们的数据表明,对SUR1调节的离子通道进行进一步研究可能有助于更好地理解脑挫伤发病机制中的关键机制,并可能确定新的靶向治疗策略。