Background

The regulation of cerebral blood flow is critical for normal brain functioning, and many physiological and pathological conditions can have long-term impacts on cerebral blood flow. However, minimally invasive tools to study chronic changes in animal models are limited.

New method

We developed a minimally invasive surgical technique (cyanoacrylate skull, CAS) allowing us to image cerebral blood flow longitudinally through the intact mouse skull using laser speckle imaging.

Results

With CAS we were able to detect acute changes in cerebral blood flow induced by hypercapnic challenge. We were also able to image cerebral blood flow dynamics with laser speckle imaging for over 100 days. Furthermore, the relative cerebral blood flow remained stable in mice from 30 days to greater than 100 days after the surgery.

Comparison with existing methods

Previously, achieving continuous long-term optical access to measure cerebral blood flow in individual vessels in a mouse model involved invasive surgery. In contrast, the CAS technique presented here is relatively non-invasive, as it allows stable optical access through an intact mouse skull.

Conclusions

The CAS technique allows researcher to chronically measure cerebral blood flow dynamics for a significant portion of a mouse’s lifespan. This approach may be useful for studying changes in blood flow due to cerebral pathology or for examining the therapeutic effects of modifying cerebral blood flow in mouse models relevant to human disease.

中文翻译：

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经颅慢性光学通路纵向测量脑血流量

背景

脑血流量的调节对正常的脑功能至关重要，许多生理和病理状况会对脑血流量产生长期影响。然而，研究动物模型慢性变化的微创工具是有限的。

新方法

我们开发了一种微创手术技术（氰基丙烯酸酯颅骨，CAS），使我们能够使用激光散斑成像对通过完整小鼠颅骨的脑血流纵向成像。

结果

通过 CAS，我们能够检测到由高碳酸血症引起的脑血流的急性变化。我们还能够使用激光散斑成像对脑血流动力学进行 100 多天的成像。此外，小鼠的相对脑血流量在手术后 30 天到超过 100 天保持稳定。

与现有方法的比较

以前，在小鼠模型中实现连续长期光学访问以测量单个血管中的脑血流涉及侵入性手术。相比之下，这里介绍的 CAS 技术是相对无创的，因为它允许通过完整的鼠标头骨进行稳定的光学访问。

结论

CAS 技术允许研究人员长期测量小鼠一生中大部分时间的脑血流动力学。这种方法可用于研究由于脑病理学引起的血流变化或检查在与人类疾病相关的小鼠模型中改变脑血流的治疗效果。