Program in Trauma, Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Neurosurgery, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF Building 823, Baltimore, MD, 21201, USA.
Neurocrit Care. 2022 Apr;36(2):612-620. doi: 10.1007/s12028-021-01350-w. Epub 2021 Oct 1.
Science continues to search for a neuroprotective drug therapy to improve outcomes after cardiac arrest (CA). The use of glibenclamide (GBC) has shown promise in preclinical studies, but its effects on neuroprognostication tools are not well understood. We aimed to investigate the effect of GBC on somatosensory evoked potential (SSEP) waveform recovery post CA and how this relates to the early prediction of functional outcome, with close attention to arousal and somatosensory recovery, in a rodent model of CA.
Sixteen male Wistar rats were subjected to 8-min asphyxia CA and assigned to GBC treatment (n = 8) or control (n = 8) groups. GBC was administered as a loading dose of 10 μg/kg intraperitoneally 10 min after the return of spontaneous circulation, followed by a maintenance dosage of 1.6 μg/kg every 8 h for 24 h. SSEPs were recorded from baseline until 150 min following CA. Coma recovery, arousal, and brainstem function, measured by subsets of the neurological deficit score (NDS), were compared between both groups. SSEP N10 amplitudes were compared between the two groups at 30, 60, 90, and 120 min post CA.
Rats treated with GBC had higher sub-NDS scores post CA, with improved arousal and brainstem function recovery (P = 0.007). Both groups showed a gradual improvement of SSEP N10 amplitude over time, from 30 to 120 min post CA. Rats treated with GBC showed significantly better SSEP recovery at every time point (P < 0.001 for 30, 60, and 90 min; P = 0.003 for 120 min). In the GBC group, the N10 amplitude recovered to baseline by 120 min post CA. Quantified Cresyl violet staining revealed a significantly greater percentage of damage in the control group compared with the GBC treatment group (P = 0.004).
Glibenclamide improves coma recovery, arousal, and brainstem function after CA with decreased number of ischemic neurons in a rat model. GBC improves SSEP recovery post CA, with N10 amplitude reaching the baseline value by 120 min, suggesting early electrophysiologic recovery with this treatment. This medication warrants further exploration as a potential drug therapy to improve functional outcomes in patients after CA.
科学继续寻找神经保护药物治疗，以改善心脏骤停 (CA) 后的预后。在临床前研究中，格列本脲 (GBC) 的应用显示出了希望，但它对神经预后工具的影响尚不清楚。我们旨在研究 GBC 对 CA 后体感诱发电位 (SSEP) 波形恢复的影响，以及如何与功能结局的早期预测相关，同时密切关注觉醒和体感恢复，在 CA 的啮齿动物模型中。
将 16 只雄性 Wistar 大鼠进行 8 分钟的窒息性 CA，并分为 GBC 治疗组 (n=8) 和对照组 (n=8)。在自主循环恢复后 10 分钟，给予 GBC 负荷剂量 10μg/kg 腹腔内给药，然后每 8 小时给予维持剂量 1.6μg/kg，持续 24 小时。在 CA 后直至 150 分钟记录 SSEP。比较两组之间的昏迷恢复、觉醒和脑干功能，通过神经功能缺损评分 (NDS) 的子集进行测量。比较 CA 后 30、60、90 和 120 分钟两组之间的 SSEP N10 振幅。
接受 GBC 治疗的大鼠 CA 后亚 NDS 评分较高，觉醒和脑干功能恢复较好 (P=0.007)。两组 SSEP N10 振幅均随时间逐渐升高，从 CA 后 30 分钟至 120 分钟。接受 GBC 治疗的大鼠在每个时间点的 SSEP 恢复均显著更好 (P<0.001 用于 30、60 和 90 分钟；P=0.003 用于 120 分钟)。在 GBC 组中，N10 振幅在 CA 后 120 分钟恢复到基线。定量的 Cresyl 紫染色显示，与 GBC 治疗组相比，对照组的损伤百分比明显更高 (P=0.004)。
在大鼠模型中，格列本脲可改善 CA 后的昏迷恢复、觉醒和脑干功能，并减少缺血神经元的数量。GBC 改善 CA 后 SSEP 恢复，N10 振幅在 120 分钟时达到基线值，表明这种治疗有早期电生理恢复。这种药物值得进一步探索，作为改善 CA 后患者功能结局的潜在药物治疗方法。
