Intracranial pressure spikes trigger spreading depolarizations
Intracranial pressure spikes trigger spreading depolarizations
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DOI：
10.1093/brain/awab256
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发表时间：
2022-01-11
期刊：
影响因子：
14.5
通讯作者：
Ayata, Cenk
中科院分区：
文献类型：
--
作者：
Oka, Fumiaki;Sadeghian, Homa;Ayata, Cenk
扩展性去极化是非常普遍的，时空间断的事件，恶化了脑损伤的结果。触发因素知之甚少，但可能与受损组织供需不匹配的突然恶化有关。颅内压的持续或短暂升高在受伤的大脑中也很普遍。在这里，使用小鼠模型的大半球缺血性中风，我们表明，轻度和短暂的颅内压升高（20或30毫米汞柱，仅3分钟），有效地触发缺血半暗带的扩展去极化（扩展去极化发生率增加4倍）。我们还表明，30毫米汞柱的颅内压尖峰一样短暂的30秒是同样有效的。相反，持续颅内压升高到相同水平30分钟并不显著增加扩展去极化率，这表明稳态平衡的突然扰动需要触发扩展去极化。激光散斑流量计一致显示组织灌注减少，双光子pO（2）显微镜显示颅内压峰值期间静脉pO（2）下降，表明氧提取分数增加，因此供需不匹配加剧。颅内压峰值期间的这些血流动力学变化与半暗带细胞外钾水平的高度可重复性增加相关。与实验数据一致，在一个回顾性系列的蛛网膜下腔出血患者中，颅内压峰值的发生率较高与广泛的去极化簇相关，具有较强的时间对应性。总之，我们的数据表明，颅内压峰值，即使是轻微和短暂的，能够触发扩散去极化。积极预防颅内压峰可能有助于减少扩散性去极化的发生，改善脑损伤后的预后。
Spreading depolarizations are highly prevalent and spatiotemporally punctuated events worsening the outcome of brain injury. Trigger factors are poorly understood but may be linked to sudden worsening in supply-demand mismatch in compromised tissue. Sustained or transient elevations in intracranial pressure are also prevalent in the injured brain. Here, using a mouse model of large hemispheric ischaemic stroke, we show that mild and brief intracranial pressure elevations (20 or 30 mmHg for just 3 min) potently trigger spreading depolarizations in ischaemic penumbra (4-fold increase in spreading depolarization occurrence). We also show that 30 mmHg intracranial pressure spikes as brief as 30 s are equally effective. In contrast, sustained intracranial pressure elevations to the same level for 30 min do not significantly increase the spreading depolarization rate, suggesting that an abrupt disturbance in the steady state equilibrium is required to trigger a spreading depolarization. Laser speckle flowmetry consistently showed a reduction in tissue perfusion, and two-photon pO(2) microscopy revealed a drop in venous pO(2) during the intracranial pressure spikes suggesting increased oxygen extraction fraction, and therefore, worsening supply-demand mismatch. These haemodynamic changes during intracranial pressure spikes were associated with highly reproducible increases in extracellular potassium levels in penumbra. Consistent with the experimental data, a higher rate of intracranial pressure spikes was associated with spreading depolarization clusters in a retrospective series of patients with aneurysmal subarachnoid haemorrhage with strong temporal correspondence. Altogether, our data show that intracranial pressure spikes, even when mild and brief, are capable of triggering spreading depolarizations. Aggressive prevention of intracranial pressure spikes may help reduce spreading depolarization occurrence and improve outcomes after brain injury.