Close association between spreading depolarization and development of infarction under experimental ischemia in anesthetized male mice.
Close association between spreading depolarization and development of infarction under experimental ischemia in anesthetized male mice.
复制标题
麻醉雄性小鼠实验性缺血下扩散去极化与梗死发展之间的密切关系。
DOI：
10.1016/j.brainres.2022.148023
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发表时间：
2022
期刊：
影响因子：
2.9
通讯作者：
Izawa Y
中科院分区：
文献类型：
--
作者：
Unekawa M;Tomita Y;Masamoto K;Kanno I;Nakahara J;Izawa Y
临床和实验证据表明，当脑灰质受到影响时，扩散性去极化（SD）通常发生在缺血性或出血性中风患者中。在这项研究中，我们评估了大脑中动脉（MCA）闭塞时脑血流量（CBF）的时空变化，并探讨了SD发生与脑梗死发展的关系。在异氟醚麻醉的雄性C57BL/6J小鼠中，用激光散斑血流显像记录了中动脉远端短暂（45 min, n = 22）或永久闭塞（n = 22）期间和之后同侧顶骨的CBF变化。术后24小时评估梗死面积。MCA闭塞后，最低CBF下降- 55.6%±8.5%，随着距离该区域的增加，CBF线性恢复。闭塞后1 - 10min， SD发生，并从核心区向中心传播，整个观察区CBF减少，正常区出现短暂充血和低充血。在37%的小鼠中，SD自发地再次发生并在缺血区域周围传播，并伴有核心区CBF的明显减少或正常区CBF的明显增加。脑血流对SDs的响应随距离核心区的远近而逐渐变化。暂时性（n = 2）或永久性（n = 4）无SD闭塞小鼠未观察到梗死。瞬时闭塞小鼠的梗死面积随着SDs数量的增加而增大。总之，我们的研究结果表明，缺血期间发生SD可能导致梗死形成和/或影响梗死发展。
Clinical and experimental evidence suggests that spreading depolarizations (SD) usually occur in patients with ischemic or hemorrhagic stroke when the gray matter of the brain is affected. In this study, we evaluated spatiotemporal changes of cerebral blood flow (CBF) during middle cerebral artery (MCA) occlusion and examined the relationship between SD occurrence and cerebral infarct development. In male isoflurane-anesthetized C57BL/6J mice, CBF changes over the ipsilateral parietal bone were recorded by laser speckle flowgraphy during and after transient (45 min, n = 22) or permanent occlusion (n = 22) of the distal MCA. Infarct volume was evaluated 24 hr after the operation. Upon MCA occlusion, CBF decreased by −55.6 ± 8.5 % in the lowest CBF and linearly recovered with increasing distance from the region. At 1–10 min after onset of occlusion, SD occurred and concentrically propagated from the core region, showing a decrease of CBF in the whole observed area along with a transient hyperemia and oligemia in the normal region. SD spontaneously re-occurred and propagated around the ischemic area in 37 % of mice, accompanied with a marked decrease of CBF in the core or a marked increase of CBF in the normal region. The CBF response to SDs gradually changed from the core to the normal area, depending upon the distance from the core region. Infarction was not observed in transiently (n = 2) or permanently (n = 4) occluded mice without SD. The infarct area tended to be larger with increasing number of SDs in transiently occluded mice. In conclusion, our findings suggest that the occurrence of SD during ischemia might elicit infarct formation and/or influence infarct development.