Cerebrospinal Fluid Sulfonylurea Receptor-1 is Associated with Intracranial Pressure and Outcome after Pediatric TBI: An Exploratory Analysis of the Cool Kids Trial.
Cerebrospinal Fluid Sulfonylurea Receptor-1 is Associated with Intracranial Pressure and Outcome after Pediatric TBI: An Exploratory Analysis of the Cool Kids Trial.
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脑脊液磺酰脲受体 1 与颅内压和儿科 TBI 后的结果相关：Cool Kids 试验的探索性分析。
DOI：
10.1089/neu.2020.7501
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发表时间：
2021
影响因子：
4.2
通讯作者：
Jha,RuchiraM
中科院分区：
文献类型：
--
作者：
Zusman,BenjaminE;Kochanek,PatrickM;Bell,MichaelJ;Adelson,PDavid;Wisniewski,StephenR;Au,AliciaK;Clark,RobertSB;Bayır,Hülya;Janesko-Feldman,Keri;Jha,RuchiraM
磺酰脲受体-1 (SUR1) 越来越被认为是导致多种形式的急性脑损伤中脑水肿、出血进展以及可能的神经元死亡的关键因素。 SUR1 抑制可能具有保护作用，并且正在创伤性脑损伤 (TBI) 和中风的 2/3 期试验中积极进行评估。在成人 TBI 中，SUR1 表达与颅内高压和挫伤扩张相关；它在儿科 TBI 中的作用仍有待探索。我们通过酶联免疫吸附测定检测了参加多中心 3 期随机对照“Cool Kids”试验的 16 名严重 TBI 儿科患者的 61 份脑脊液 (CSF) 样本和 7 名非脑损伤儿科对照患者的 SUR1 表达。线性混合模型评估了受伤后前 7 天的平均 SUR1 和颅内压 (ICP) 以及儿童格拉斯哥结果量表扩展 (GOS-E Peds) 之间的关联。 SUR1 在对照 CSF 中检测不到，但在 16 名 TBI 患者中，有 9 名患者与对照相比有所增加。平均 SUR1 与年龄、性别或治疗性低温无关。初始格拉斯哥昏迷评分每增加 1 分，脑脊液 SUR1 就会减少 1.68ng/mL。 CSF SUR1 与 7 天内 ICP 增加 (b = 0.73,p= 0.004) 以及更差（较高）的 GOS-E Peds 评分 (b = 0.24,p= 0.004) 相关。在这项探索性儿科研究中，CSF SUR1 在对照组中检测不到，而在严重 TBI 中则不同程度升高。平均 CSF SUR1 浓度与 ICP 和结果相关。这些发现与我们之前在患有严重 TBI 的成人中的报告不同，在该报告中普遍检测到了 SUR1。 SUR1 可能是儿科 TBI 子集中的一个可行的治疗靶点，有必要进行进一步的研究。
Sulfonylurea receptor-1 (SUR1) is recognized increasingly as a key contributor to cerebral edema, hemorrhage progression, and possibly neuronal death in multiple forms of acute brain injury. SUR1 inhibition may be protective and is actively undergoing evaluation in Phase-2/3 trials of traumatic brain injury (TBI) and stroke. In adult TBI, SUR1 expression is associated with intracranial hypertension and contusion expansion; its role in pediatric TBI remains unexplored. We tested 61 cerebrospinal fluid (CSF) samples from 16 pediatric patients with severe TBI enrolled in the multicenter Phase-3 randomized controlled “Cool Kids” trial and seven non-brain injured pediatric controls for SUR1 expression by enzyme-linked immunosorbent assay. Linear mixed models evaluated associations between mean SUR1 and intracranial pressure (ICP) over the first seven days and pediatric Glasgow Outcome Scale-Extended (GOS-E Peds) over the initial year after injury. SUR1 was undetectable in control CSF and increased versus control in nine of 16 patients with TBI. Mean SUR1 was not associated with age, sex, or therapeutic hypothermia. Each 1-point increase in initial Glasgow Coma Score was associated with a 1.68 ng/mL decrease in CSF SUR1. The CSF SUR1 was associated with increased ICP over seven days (b = 0.73,p= 0.004) and worse (higher) GOS-E Peds score (b = 0.24,p= 0.004). In this exploratory pediatric study, CSF SUR1 was undetectable in controls and variably elevated in severe TBI. Mean CSF SUR1 concentration was associated with ICP and outcome. These findings are distinct from our previous report in adults with severe TBI, where SUR1 was detected universally. SUR1 may be a viable therapeutic target in a subset of pediatric TBI, and further study is warranted.