Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Drug Alcohol Depend. 2020 Jan 1;206:107637. doi: 10.1016/j.drugalcdep.2019.107637. Epub 2019 Oct 18.
Cocaine has a variety of negative effects on the central nervous system, including reports of decreased barrier function of brain microvascular endothelial cells. However, few studies have directly shown the effects of cocaine on blood-brain barrier (BBB) function in vivo. The miniature integrated fluorescence microscope (i.e., miniscope) technology was used to visualize cocaine-induced changes in BBB permeability in awake, freely-moving rats.
The miniscope was implanted in the prefrontal cortex of adult male rats. After recovery and acclimation, rats received an injection of cocaine (5-20 mg/kg ip) 15 minutes following iv infusion of sodium fluorescein, a low molecular weight tracer. Fluorescence intensity was recordedin vivo via the miniscope for 30 minutes or 24 hours post cocaine administration and served as an indicator of BBB permeability.
Results demonstrate that cocaine increased the sodium fluorescein extravasation in brain microcirculation in a dose-dependent manner 30 minutes, but not 24 hours after administration.
We report for the first time using direct visualization of brain microcirculation with the miniscope technology in awake, freely-moving rats, that acute cocaine administration produced a transient increase in the BBB permeability.
可卡因对中枢神经系统有多种负面影响，包括报道称其会降低脑微血管内皮细胞的屏障功能。然而，很少有研究直接表明可卡因对体内血脑屏障（BBB）功能的影响。微型集成荧光显微镜（即 miniscope）技术用于可视化可卡因诱导的清醒、自由活动大鼠 BBB 通透性的变化。
将 miniscope 植入成年雄性大鼠的前额皮质。恢复和适应后，大鼠在静脉内输注低分子重量示踪剂荧光素钠 15 分钟后，接受可卡因（5-20mg/kg ip）注射。通过 miniscope 在可卡因给药后 30 分钟或 24 小时内进行体内荧光强度记录，作为 BBB 通透性的指标。
结果表明，可卡因在给药后 30 分钟而非 24 小时呈剂量依赖性增加了脑微循环中的荧光素钠外渗。
我们首次报告了使用 miniscope 技术在清醒、自由活动的大鼠中直接可视化脑微循环，发现急性可卡因给药会导致 BBB 通透性短暂增加。
