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.

中文翻译：

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脑脊液磺酰脲受体 1 与小儿 TBI 后颅内压和结局相关：酷儿试验的探索性分析

磺脲类受体 1 (SUR1) 越来越被认为是多种形式的急性脑损伤中脑水肿、出血进展和可能的神经元死亡的关键因素。SUR1 抑制可能具有保护作用，并且正在积极地在创伤性脑损伤 (TBI) 和中风的 2/3 期试验中进行评估。在成人 TBI 中，SUR1 表达与颅内高压和挫伤扩大有关；它在儿科 TBI 中的作用仍未得到探索。我们通过酶联免疫吸附试验测试了来自 16 名严重 TBI 儿科患者的 61 份脑脊液 (CSF) 样本，这些患者参加了多中心 3 期随机对照“Cool Kids”试验和 7 名非脑损伤儿科对照的 SUR1 表达。线性混合模型评估了前 7 天的平均 SUR1 和颅内压 (ICP) 之间的关联，以及受伤后第一年的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，并且在 16 名 TBI 患者中有 9 名与对照相比增加。平均 SUR1 与年龄、性别或低温治疗无关。初始格拉斯哥昏迷评分每增加 1 分，CSF SUR1 下降 1.68 ng/mL。CSF SUR1 与 7 天内 ICP 增加相关（b = 0.73，初始格拉斯哥昏迷评分每增加 1 分，CSF SUR1 下降 1.68 ng/mL。CSF SUR1 与 7 天内 ICP 增加相关（b = 0.73，初始格拉斯哥昏迷评分每增加 1 分，CSF SUR1 下降 1.68 ng/mL。CSF SUR1 与 7 天内 ICP 增加相关（b = 0.73，p  = 0.004）和更差（更高）的 GOS-E Peds 评分（b = 0.24，p  = 0.004）。在这项探索性儿科研究中，CSF SUR1 在对照组中检测不到，在严重 TBI 中出现不同程度的升高。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 的成年人中的报告不同，后者普遍检测到 SUR1。SUR1 可能是小儿 TBI 子集中的可行治疗靶点，需要进一步研究。