Du Congwu, Jeong Hyomin, Koretsky Alan P, Pan Yingtian
Stony Brook University, Department of Biomedical Engineering, Stony Brook, New York, United States.
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States.
Neurophotonics. 2025 Jan;12(Suppl 1):S14611. doi: 10.1117/1.NPh.12.S1.S14611. Epub 2025 May 28.
Cocaine exerts effects on vascular and cellular functions in the brain. The interactions among cerebrovasculature, neurons, and astrocytes and their dynamic changes during exposure complicate the understanding of its effects. Therefore, there is a need for simultaneous, multiparameter measurements to accurately distinguish these effects.
A multimodal optical imaging approach that is tailored to investigate cocaine's effects on cerebrovasculature, neurons, and astrocytes in high-spatiotemporal resolution and large field of view is presented with comparisons to other modalities.
This approach integrates optical coherence tomography, fluorescence, and spectral absorption imaging to permit high-resolution imaging of 3D cerebrovessels, cerebral blood flow (CBF), changes in oxygenated/deoxygenated hemoglobin, and large-scale cellular activities via intracellular calcium fluorescence expressed through genetically encoded calcium indicators in the mouse cortex.
Results show that cocaine induces vasoconstriction and reduces CBF, thus increasing the susceptibility of the brain to ischemia with chronic exposure. Moreover, cocaine alters neuronal activity and frontal responses to deep brain stimulation.
These findings on cocaine's effects on the neuro-astroglial-vascular network in the prefrontal cortex highlight the unique capacity of optical imaging to reveal the cellular and vascular mechanisms underlying cocaine's neurotoxic effects on brain function.
可卡因对大脑的血管和细胞功能产生影响。脑血管、神经元和星形胶质细胞之间的相互作用及其在暴露过程中的动态变化使人们对其影响的理解变得复杂。因此，需要进行同步的多参数测量以准确区分这些影响。
提出一种多模态光学成像方法，该方法专为以高时空分辨率和大视野研究可卡因对脑血管、神经元和星形胶质细胞的影响而量身定制，并与其他模态进行比较。
该方法整合了光学相干断层扫描、荧光和光谱吸收成像，以通过小鼠皮层中基因编码钙指示剂表达的细胞内钙荧光对三维脑血管、脑血流量（CBF）、氧合/脱氧血红蛋白变化和大规模细胞活动进行高分辨率成像。
结果表明，可卡因会引起血管收缩并降低脑血流量，因此长期暴露会增加大脑对缺血的易感性。此外，可卡因会改变神经元活动以及对深部脑刺激的额叶反应。
这些关于可卡因对前额叶皮质神经-星形胶质-血管网络影响的发现突出了光学成像揭示可卡因对脑功能神经毒性作用背后的细胞和血管机制的独特能力。
