Department of Medical Physics and Informatics, Faculty of Science and Informatics, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Cerebral Blood Flow and Metabolism Research Group, Hungarian Centre of Excellence for Molecular Medicine, University of Szeged, Szeged, Hungary.
Neurocrit Care. 2022 Jun;37(Suppl 1):112-122. doi: 10.1007/s12028-021-01393-z. Epub 2021 Dec 2.
In ischemic stroke, cerebral autoregulation and neurovascular coupling may become impaired. The cerebral blood flow (CBF) response to spreading depolarization (SD) is governed by neurovascular coupling. SDs recur in the ischemic penumbra and reduce neuronal viability by the insufficiency of the CBF response. Autoregulatory failure and SD may coexist in acute brain injury. Here, we set out to explore the interplay between the impairment of cerebrovascular autoregulation, SD occurrence, and the evolution of the SD-coupled CBF response.
Incomplete global forebrain ischemia was created by bilateral common carotid artery occlusion in isoflurane-anesthetized rats, which induced ischemic SD (iSD). A subsequent SD was initiated 20-40 min later by transient anoxia SD (aSD), achieved by the withdrawal of oxygen from the anesthetic gas mixture for 4-5 min. SD occurrence was confirmed by the recording of direct current potential together with extracellular K concentration by intracortical microelectrodes. Changes in local CBF were acquired with laser Doppler flowmetry. Mean arterial blood pressure (MABP) was continuously measured via a catheter inserted into the left femoral artery. CBF and MABP were used to calculate an index of cerebrovascular autoregulation (rCBFx). In a representative imaging experiment, variation in transmembrane potential was visualized with a voltage-sensitive dye in the exposed parietal cortex, and CBF maps were generated with laser speckle contrast analysis.
Ischemia induction and anoxia onset gave rise to iSD and aSD, respectively, albeit aSD occurred at a longer latency, and was superimposed on a gradual elevation of K concentration. iSD and aSD were accompanied by a transient drop of CBF (down to 11.9 ± 2.9 and 7.4 ± 3.6%, iSD and aSD), but distinctive features set the hypoperfusion transients apart. During iSD, rCBFx indicated intact autoregulation (rCBFx < 0.3). In contrast, aSD was superimposed on autoregulatory failure (rCBFx > 0.3) because CBF followed the decreasing MABP. CBF dropped 15-20 s after iSD, but the onset of hypoperfusion preceded aSD by almost 3 min. Taken together, the CBF response to iSD displayed typical features of spreading ischemia, whereas the transient CBF reduction with aSD appeared to be a passive decrease of CBF following the anoxia-related hypotension, leading to aSD.
We propose that the dysfunction of cerebrovascular autoregulation that occurs simultaneously with hypotension transients poses a substantial risk of SD occurrence and is not a consequence of SD. Under such circumstances, the evolving SD is not accompanied by any recognizable CBF response, which indicates a severely damaged neurovascular coupling.
在缺血性中风中，脑自动调节和神经血管耦合可能会受损。脑血流 (CBF) 对扩散性去极化 (SD) 的反应受神经血管耦合的控制。SD 在缺血半影区反复发生，并通过 CBF 反应不足降低神经元活力。急性脑损伤中可能同时存在自动调节衰竭和 SD。在这里，我们旨在探索脑血管自动调节受损、SD 发生和与 SD 相关的 CBF 反应演变之间的相互作用。
在异氟烷麻醉的大鼠中通过双侧颈总动脉闭塞创建不完全性全脑缺血，从而诱导缺血性 SD (iSD)。随后通过短暂缺氧 SD (aSD) 在 20-40 分钟后启动另一个 SD，通过从麻醉气体混合物中抽出氧气 4-5 分钟来实现。通过颅内微电极记录直流电位和细胞外 K 浓度来确认 SD 的发生。使用激光多普勒流量测量法获得局部 CBF 的变化。通过插入左股动脉的导管连续测量平均动脉血压 (MABP)。使用 CBF 和 MABP 计算脑血管自动调节指数 (rCBFx)。在代表性的成像实验中，用电压敏感染料可视化暴露的顶叶皮层中的跨膜电位变化，并使用激光散斑对比分析生成 CBF 图。
诱导缺血和缺氧开始分别引起 iSD 和 aSD，尽管 aSD 的潜伏期较长，并且叠加在逐渐升高的 K 浓度上。iSD 和 aSD 伴随着 CBF 的短暂下降（分别降至 11.9 ± 2.9%和 7.4 ± 3.6%，iSD 和 aSD），但特征性表现使低灌注瞬变分开。在 iSD 期间，rCBFx 表明自动调节完好（rCBFx <0.3）。相比之下，aSD 叠加在自动调节衰竭上（rCBFx >0.3），因为 CBF 随降低的 MABP 而变化。iSD 后 15-20 秒 CBF 下降，但低灌注的起始时间比 aSD 早近 3 分钟。总的来说，iSD 的 CBF 反应显示出扩散性缺血的典型特征，而 aSD 时短暂的 CBF 降低似乎是由于缺氧相关低血压导致的 CBF 被动下降引起的 aSD。
我们提出，同时发生的低血压瞬变引起的脑血管自动调节功能障碍是 SD 发生的重大风险，而不是 SD 的结果。在这种情况下，进行性 SD 没有任何可识别的 CBF 反应，这表明神经血管耦合严重受损。
