Background

Endovascular thrombectomy (EVT) is highly effective but may also lead to hemorrhagic transformation (HT) and edema, which may be more pronounced in severe ischemia. We sought to determine whether glibenclamide can attenuate HT and edema in a severe ischemia-reperfusion model that reflects EVT.

Methods

Using a transient middle cerebral artery occlusion (tMCAo) rodent model of stroke, we studied two rat cohorts, one without rt-PA and a second cohort treated with rt-PA. Glibenclamide or vehicle control was administered as an intravenous bolus at reperfusion, followed by continuous subcutaneous administration with an osmotic pump.

Results

Compared to vehicle control, glibenclamide improved neurological outcome (median 7, interquartile range [IQR 6–8] vs. control median 6 [IQR 0–6], p = 0.025), reduced stroke volume (323 ± 42 vs. 484 ± 60 mm³, p < 0.01), swelling volume (10 ± 4 vs. 28 ± 7%, p < 0.01) and water content (84 ± 1 vs. 85 ± 1%, p < 0.05). Glibenclamide administration also reduced HT based on ECASS criteria, densitometry (0.94 ± 0.1 vs. 1.15 ± 0.2, p < 0.01), and quantitative hemoglobin concentration (2.7 ± 1.5 vs. 6.2 ± 4.6 uL, p = 0.011). In the second cohort with rt-PA coadministration, concordant effects on HT were observed with glibenclamide.

Conclusions

Taken together, these studies demonstrated that glibenclamide reduced the amount of edema and HT after severe ischemia. This study suggests that co-administration of glibenclamide may be worth further study in severe stroke patients treated with EVT with or without IV rt-PA.

中文翻译：

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连续格列本脲预防严重缺血再灌注啮齿动物模型的出血性转化

背景

血管内血栓切除术 (EVT) 非常有效，但也可能导致出血性转化 (HT) 和水肿，这在严重缺血时可能更为明显。我们试图确定格列本脲是否可以在反映 EVT 的严重缺血再灌注模型中减轻 HT 和水肿。

方法

使用短暂的大脑中动脉闭塞 (tMCAo) 啮齿动物中风模型，我们研究了两组大鼠，一组没有 rt-PA，另一组接受 rt-PA 治疗。格列本脲或载体对照在再灌注时作为静脉推注给药，然后用渗透泵连续皮下给药。

结果

与载体对照相比，格列本脲改善了神经功能结果（中位数 7，四分位距 [IQR 6-8] 与对照中位数 6 [IQR 0-6]，p  = 0.025），每搏输出量减少（323 ± 42 vs. 484 ± 60 mm ³ , p  < 0.01)、膨胀体积 (10 ± 4 vs. 28 ± 7%, p  < 0.01) 和水含量 (84 ± 1 vs. 85 ± 1%, p  < 0.05)。根据 ECASS 标准、光密度测定法（0.94 ± 0.1 vs. 1.15 ± 0.2，p  < 0.01）和定量血红蛋白浓度（2.7 ± 1.5 vs. 6.2 ± 4.6 uL，p  = 0.011），格列本脲给药还可以降低 HT。在 rt-PA 共同给药的第二个队列中，格列本脲对 HT 的影响一致。

结论

总之，这些研究表明，格列本脲可减少严重缺血后的水肿和 HT 量。这项研究表明，格列本脲的共同给药可能值得在接受或不接受 IV rt-PA 的 EVT 治疗的严重卒中患者中进一步研究。