Animal models of stroke are used extensively to study the mechanisms involved in the acute and chronic phases of recovery following stroke. A translatable animal model that closely mimics the mechanisms of a human stroke is essential in understanding recovery processes as well as developing therapies that improve functional outcomes. We describe a photothrombosis stroke model that is capable of targeting a single distal pial branch of the middle cerebral artery with minimal damage to the surrounding parenchyma in awake head-fixed mice. Mice are implanted with chronic cranial windows above one hemisphere of the brain that allow optical access to study recovery mechanisms for over a month following occlusion. Additionally, we study the effect of laser spot size used for occlusion and demonstrate that a spot size with small axial and lateral resolution has the advantage of minimizing unwanted photodamage while still monitoring macroscopic changes to cerebral blood flow during photothrombosis. We show that temporally guiding illumination using real-time feedback of blood flow dynamics also minimized unwanted photodamage to the vascular network. Finally, through quantifiable behavior deficits and chronic imaging we show that this model can be used to study recovery mechanisms or the effects of therapeutics longitudinally.

中文翻译：

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通过光血栓形成的靶向性颈动脉闭塞的清醒慢性小鼠模型。

中风的动物模型被广泛用于研究中风后恢复的急性和慢性阶段的机制。紧密模仿人类中风机制的可翻译动物模型对于理解恢复过程以及开发改善功能结局的疗法至关重要。我们描述了一种光血栓形成性中风模型，该模型能够靶向清醒的头部固定小鼠周围中脑实质的最小损害，而靶向中脑动脉的单个远侧梨状分支。小鼠在大脑的一个半球上方植入了慢性颅窗，可以在闭塞后一个多月内通过光学途径研究恢复机制。另外，我们研究了用于封闭的激光光斑尺寸的影响，并证明了具有较小轴向和横向分辨率的光斑尺寸具有最大程度地减少不必要的光损伤的优点，同时仍可监控光血栓形成过程中脑血流的宏观变化。我们显示使用血流动力学的实时反馈的时间引导照明还可以最大程度地减少对血管网络的有害光损伤。最后，通过可量化的行为缺陷和慢性成像，我们表明该模型可用于纵向研究康复机制或治疗效果。我们表明，使用血流动力学的实时反馈进行时间导向照明也可以最大程度地减少对血管网络的有害光损伤。最后，通过可量化的行为缺陷和慢性成像，我们表明该模型可用于纵向研究康复机制或治疗效果。我们显示使用血流动力学的实时反馈的时间引导照明还可以最大程度地减少对血管网络的有害光损伤。最后，通过可量化的行为缺陷和慢性成像，我们表明该模型可用于纵向研究康复机制或治疗效果。