Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, USA.
Mol Psychiatry. 2012 Oct;17(10):1017-25. doi: 10.1038/mp.2011.160. Epub 2011 Nov 29.
Cocaine-induced stroke is among the most serious medical complications associated with its abuse. However, the extent to which acute cocaine may induce silent microischemia predisposing the cerebral tissue to neurotoxicity has not been investigated; in part, because of limitations of current neuroimaging tools, that is, lack of high spatiotemporal resolution and sensitivity to simultaneously measure cerebral blood flow (CBF) in vessels of different calibers (including capillaries) quantitatively and over a large field of view. Here we combine ultrahigh-resolution optical coherence tomography to enable tracker-free three-dimensional (3D) microvascular angiography and a new phase-intensity-mapping algorithm to enhance the sensitivity of 3D optical Doppler tomography for simultaneous capillary CBF quantization. We apply the technique to study the responses of cerebral microvascular networks to single and repeated cocaine administration in the mouse somatosensory cortex. We show that within 2-3 min after cocaine administration CBF markedly decreased (for example, 70%), but the magnitude and recovery differed for the various types of vessels; arterioles had the fastest recovery (5 min), capillaries varied drastically (from 4-20 min) and venules showed relatively slower recovery (~12 min). More importantly, we showed that cocaine interrupted CBF in some arteriolar branches for over 45 min and this effect was exacerbated with repeated cocaine administration. These results provide evidence that cocaine doses within the range administered by drug abusers induces cerebral microischemia and that these effects are exacerbated with repeated use. Thus, cocaine-induced microischemia is likely to be a contributor to its neurotoxic effects.
可卡因引起的中风是与滥用可卡因相关的最严重的医学并发症之一。然而，急性可卡因在多大程度上可能引起沉默性微缺血，从而使脑组织容易受到神经毒性的影响，这一点尚未得到研究；部分原因是由于当前神经影像学工具的局限性，即缺乏高时空分辨率，并且无法定量且在大视场范围内同时测量不同口径（包括毛细血管）的血管中的脑血流 (CBF)。在这里，我们结合超高分辨率光相干断层扫描来实现无跟踪的三维（3D）微血管血管造影术，以及一种新的相位-强度映射算法来提高 3D 光学多普勒断层扫描的灵敏度，以同时量化毛细血管 CBF。我们应用该技术研究了在小鼠体感皮层中单次和重复给予可卡因后大脑微血管网络的反应。我们表明，在可卡因给药后 2-3 分钟内，CBF 明显下降（例如，约 70%），但各种类型的血管的幅度和恢复情况不同；小动脉恢复最快（约 5 分钟），毛细血管变化很大（4-20 分钟），小静脉恢复相对较慢（约 12 分钟）。更重要的是，我们表明可卡因中断了一些小动脉分支中的 CBF 超过 45 分钟，并且这种作用在重复给予可卡因时加剧。这些结果提供了证据表明，滥用者给予的可卡因剂量范围内会引起大脑微缺血，并且这种作用在重复使用时会加剧。因此，可卡因引起的微缺血可能是其神经毒性作用的一个促成因素。
