Early cortical infarcts are common in poor-grade patients after aneurysmal subarachnoid haemorrhage. There are no animal models of these lesions and mechanisms are unknown, although mass cortical spreading depolarizations are hypothesized as a requisite mechanism and clinical marker of infarct development. Here we studied acute sequelae of subarachnoid haemorrhage in the gyrencephalic brain of propofol-anaesthetized juvenile swine using subdural electrode strips (electrocorticography) and intraparenchymal neuromonitoring probes. Subarachnoid infusion of 1–2 ml of fresh blood at 200 µl/min over cortical sulci caused clusters of spreading depolarizations (count range: 12–34) in 7/17 animals in the ipsilateral but not contralateral hemisphere in 6 h of monitoring, without meaningful changes in other variables. Spreading depolarization clusters were associated with formation of sulcal clots (P < 0.01), a high likelihood of adjacent cortical infarcts (5/7 versus 2/10, P < 0.06), and upregulation of cyclooxygenase-2 in ipsilateral cortex remote from clots/infarcts. In a second cohort, infusion of 1 ml of clotted blood into a sulcus caused spreading depolarizations in 5/6 animals (count range: 4–20 in 6 h) and persistent thick clots with patchy or extensive infarction of circumscribed cortex in all animals. Infarcts were significantly larger after blood clot infusion compared to mass effect controls using fibrin clots of equal volume. Haematoxylin and eosin staining of infarcts showed well demarcated zones of oedema and hypoxic-ischaemic neuronal injury, consistent with acute infarction. The association of spreading depolarizations with early brain injury was then investigated in 23 patients [14 female; age (median, quartiles): 57 years (47, 63)] after repair of ruptured anterior communicating artery aneurysms by clip ligation (n = 14) or coiling (n = 9). Frontal electrocorticography [duration: 54 h (34, 66)] from subdural electrode strips was analysed over Days 0–3 after initial haemorrhage and magnetic resonance imaging studies were performed at ∼ 24–48 h after aneurysm treatment. Patients with frontal infarcts only and those with frontal infarcts and/or intracerebral haemorrhage were both significantly more likely to have spreading depolarizations (6/7 and 10/12, respectively) than those without frontal brain lesions (1/11, P’s < 0.05). These results suggest that subarachnoid clots in sulci/fissures are sufficient to induce spreading depolarizations and acute infarction in adjacent cortex. We hypothesize that the cellular toxicity and vasoconstrictive effects of depolarizations act in synergy with direct ischaemic effects of haemorrhage as mechanisms of infarct development. Results further validate spreading depolarizations as a clinical marker of early brain injury and establish a clinically relevant model to investigate causal pathologic sequences and potential therapeutic interventions.

中文翻译：

---

蛛网膜下腔血会急性引起去极化和早期皮层梗死

在动脉瘤性蛛网膜下腔出血后的不良患者中，早期皮质梗死很常见。尽管假定皮层弥散性去极化是梗死发展的必要机制和临床标志，但尚无动物模型可了解这些病变，其机制尚不清楚。在这里，我们使用硬膜下电极条（皮层电图）和实质内神经监测探针研究了异丙酚麻醉的幼猪的脑脊液中蛛网膜下腔出血的急性后遗症。蛛网膜下腔以200 µl / min的速度在皮质沟内输注1-2 ml新鲜血液，导致在6小时的监测中，同侧但非对侧半球中的7/17只动物出现了成簇的去极化分布（计数范围：12-34）。其他变量的有意义的变化。P <0.01），邻近皮层梗死的可能性很高（5/7比2/10，P<0.06），并且远离血凝块/梗塞的同侧皮质中环氧合酶2的上调。在第二个队列中，向沟中注入1 ml凝结的血液导致5/6只动物（在6小时内计数范围：4–20）扩散去极化，并在所有动物中持续出现厚厚的凝块，并带有局限性皮质的斑块状或广泛性梗塞。与使用等体积血纤蛋白凝块的质量效应对照相比，输血凝块后的梗塞明显更大。苏木精和曙红对梗塞的染色显示水肿和缺氧缺血性神经元损伤的界限清楚，与急性梗塞一致。然后在23例患者中调查了扩展去极化与早期脑损伤的相关性[14名女性； 14名女性。年龄（中位数，四分位数）：57岁（47岁，n = 14）或盘绕（n = 9）。在初次出血后的第0–3天分析了硬膜下电极带的额叶皮质电图[持续时间：54 h（34，66）]，并在动脉瘤治疗后约24–48 h进行了磁共振成像研究。患者仅有额叶梗死和那些具有正面梗死和/或颅内出血均显著更可能有蔓延比去极化（6/7和10/12，分别），而额叶脑损伤（1/11，P的<0.05）。这些结果表明，龈沟/缝隙中的蛛网膜下腔凝块足以在邻近的皮质中诱发扩散性去极化和急性梗塞。我们假设去极化的细胞毒性和血管收缩作用与出血的直接缺血效应协同作用，是梗死发展的机制。结果进一步验证了传播去极化作为早期脑损伤的临床标志，并建立了临床相关模型以研究因果病理序列和潜在的治疗干预措施。