Shimamura Norihito, Fumoto Toshio, Naraoka Masato, Katagai Takeshi, Fujiwara Nozomi, Katayama Kosuke, Kinoshita Shouhei, Yanagiya Keita, Sasaki Takao, Kurose Akira, Ohkuma Hiroki
Department of Neurosurgery, Hirosaki University Graduate School of Medicine, 5-Zaihuchou, Hirosaki, Aomori Pref, 036-8562, Japan.
Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, , Aomori Pref, 036-8562s, Japan.
Transl Stroke Res. 2021 Oct;12(5):785-790. doi: 10.1007/s12975-020-00875-0. Epub 2020 Nov 27.
Pathophysiological findings of early brain injury in humans have not permitted conclusive determinations. We explored the essence of this phenomenon by taking intraoperative cortical specimens of Hunt-Kosnik grades IV~V (poor-grade) subarachnoid hemorrhages (SAH). From 2013 to 2017, we treated 39 consecutive poor-grade patients in 226 cases of aneurysmal SAH. Fourteen of the 39 patients agreed to this study following written informed consent. We took specimens from untouched areas prior to surgical intervention: cortex near the ruptured aneurysm for clipping, convexity cortex for cerebral ventricular drainage. Cortical specimens were stained with hematoxylin-eosin, anti-cleaved caspase-3, and anti-DNA/RNA damage staining. Positive signals were calculated in six random, high-power fields for quantitative assessment. Double immunofluorescence was done to evaluate neural damage. Chi-square analyses were carried out to assess the correlation between the Glasgow Outcome Scale at 90 days after the ictus and the number of positive cells. Cortical specimens were taken at 12.7 ± 7.00 h after the first ictus. All 14 cases showed dense nuclei, with the appearance of acidic and shrunken cytoplasms. Diffuse positivity of anti-cleaved caspase-3 and anti-DNA/RNA damage was detected. Cleaved caspase-3 was detected in 68% of neurons, and DNA/RNA damage was detected in 64% of neurons. Positive reactions of both antibodies indicated poor outcome. With poor-grade cases, irreversible ischemic, apoptotic, and oxidative changes were detected in the cerebral cortex within several hours after the ictus. Those changes occurred far from the aneurysm. Our findings suggest that a revolution is needed in the treatment strategy for poor-grade SAH.
人类早期脑损伤的病理生理研究结果尚未得出确凿结论。我们通过获取Hunt-Kosnik分级为IV~V级（低级别）蛛网膜下腔出血（SAH）患者的术中皮质标本，来探究这一现象的本质。2013年至2017年，在226例动脉瘤性SAH患者中，我们连续治疗了39例低级别患者。39例患者中有14例在签署书面知情同意书后同意参与本研究。我们在手术干预前从未触及区域获取标本：靠近破裂动脉瘤处的皮质用于夹闭，脑凸面皮质用于脑室引流。皮质标本用苏木精-伊红、抗切割的半胱天冬酶-3和抗DNA/RNA损伤染色。在六个随机的高倍视野中计算阳性信号进行定量评估。进行双重免疫荧光以评估神经损伤。进行卡方分析以评估发病后90天格拉斯哥预后评分与阳性细胞数量之间的相关性。皮质标本在首次发病后12.7±7.00小时获取。所有14例均显示细胞核致密，细胞质呈酸性且萎缩。检测到抗切割的半胱天冬酶-3和抗DNA/RNA损伤的弥漫性阳性。在68%的神经元中检测到切割的半胱天冬酶-3，在64%的神经元中检测到DNA/RNA损伤。两种抗体的阳性反应均表明预后不良。在低级别病例中，发病后数小时内大脑皮质中检测到不可逆的缺血、凋亡和氧化变化。这些变化发生在远离动脉瘤的部位。我们的研究结果表明，低级别SAH的治疗策略需要一场变革。
