In vivo imaging of nitric oxide in the male rat brain exposed to a shock wave
In vivo imaging of nitric oxide in the male rat brain exposed to a shock wave
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DOI：
10.1002/jnr.25172
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发表时间：
2023-02-06
影响因子：
4.2
通讯作者：
Sato，Shunichi
中科院分区：
文献类型：
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作者：
Kawauchi，Satoko;Inaba，Masaki;Sato，Shunichi
虽然许多研究表明脑血管功能障碍参与了冲击波诱导的创伤性脑损伤（bTBI）的病理生物学，但其确切机制及其如何影响bTBI的结局尚未完全了解。我们之前的研究表明，暴露于激光诱导冲击波（LISW）的大鼠大脑中发生了皮质扩展性去极化（CSD）和随后的长期低血/低氧血症。我们假设这种血流动力学异常与冲击波诱导的一氧化氮（NO）生成有关。在这项研究中，为了验证这一假设，我们使用了一种NO敏感的荧光探针，二氨基荧光素-2二乙酸酯（DA-2），对暴露于轻度脉冲LISW的雄性Sprague-Dawley大鼠的大脑进行了真实的实时体内成像。在暴露后10-30 min期间，我们观察到沿软脑膜小动脉壁沿着最强的荧光，指示NO产生，与CSD发生平行。该暴露后阶段也与血流动力学异常的早期阶段一致。虽然在暴露前24小时接受硝基-L-精氨酸甲酯（L-NAME）药理学NO合酶抑制的大鼠中测量的小动脉壁荧光变化显示出与LISW暴露的CSD大鼠中观察到的变化相似的时间曲线，但其强度水平相当低;这表明NOS部分参与了冲击波诱导的NO产生。据我们所知，这是第一个真实的NO在大鼠脑中的体内成像，证实了NO参与冲击波诱导的血流动力学损伤。最后，我们也指出本研究的局限性及未来的研究方向。
While numerous studies have suggested the involvement of cerebrovascular dysfunction in the pathobiology of blast‐induced traumatic brain injury (bTBI), its exact mechanisms and how they affect the outcome of bTBI are not fully understood. Our previous study showed the occurrence of cortical spreading depolarization (CSD) and subsequent long‐lasting oligemia/hypoxemia in the rat brain exposed to a laser‐induced shock wave (LISW). We hypothesized that this hemodynamic abnormality is associated with shock wave‐induced generation of nitric oxide (NO). In this study, to verify this hypothesis, we used an NO‐sensitive fluorescence probe, diaminofluorescein‐2 diacetate (DAF‐2 DA), for real‐time in vivo imaging of male Sprague–Dawley rats' brain exposed to a mild‐impulse LISW. We observed the most intense fluorescence, indicative of NO production, along the pial arteriolar walls during the period of 10–30 min post‐exposure, parallel with CSD occurrence. This post‐exposure period also coincided with the early phase of hemodynamic abnormalities. While the changes in arteriolar wall fluorescence measured in rats receiving pharmacological NO synthase inhibition by nitro‐L‐arginine methyl ester (L‐NAME) 24 h before exposure showed a temporal profile similar to that of changes observed in LISW‐exposed rats with CSD, their intensity level was considerably lower; this suggests partial involvement of NOS in shock wave‐induced NO production. To the best of our knowledge, this is the first real‐time in vivo imaging of NO in rat brain, confirming the involvement of NO in shock‐wave‐induced hemodynamic impairments. Finally, we have outlined the limitations of this study and our future research directions.