Biomedical Engineering Institute, École Polytechnique de Montréal, Montréal, QC, Canada; Montreal Heart Institute, Montréal, QC, Canada; Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.
Biomedical Engineering Institute, École Polytechnique de Montréal, Montréal, QC, Canada; Montreal Heart Institute, Montréal, QC, Canada.
Neurosci Lett. 2019 Apr 23;699:160-166. doi: 10.1016/j.neulet.2019.02.007. Epub 2019 Feb 7.
Compromised oxygen supply to cerebral tissue could be an important mechanism contributing to age-related cognition decline. We recently showed in awake mice that resting cerebral tissue pO decreases with age, a phenomenon that manifests mainly after middle-age. To extend these findings, here we aimed to study how tissue pO response to neuronal stimulation is affected by aging. We used two-photon phosphorescence lifetime microscopy to directly measure the brain tissue pO response to whisker stimulation in healthy awake young, middle-aged and old mice. We show that despite a decrease in baseline tissue pO, the amplitude of the tissue pO response to stimulation is well preserved with age. However, the response dynamics are altered towards a slower response with reduced post-stimulus undershoot in older ages, possibly due to stiffer vessel wall among other factors. An estimation of the net oxygen consumption rate using a modified Krogh model suggests that the O overshoot during stimulation may be necessary to secure a higher capillary O delivery to the tissue proportional to increased CMRO to maintain the capillary tissue pO. It was observed that the coupling between the CMRO and capillary O delivery is preserved with age.
脑组织供氧受损可能是导致与年龄相关的认知能力下降的重要机制。我们最近在清醒的小鼠中表明，静息脑组织 pO 随年龄增长而降低，这一现象主要在中年后表现出来。为了扩展这些发现，我们旨在研究神经元刺激对脑组织 pO 的反应如何受到衰老的影响。我们使用双光子磷光寿命显微镜直接测量健康清醒的年轻、中年和老年小鼠的胡须刺激引起的脑组织 pO 反应。我们表明，尽管基础组织 pO 下降，但刺激引起的组织 pO 反应幅度随年龄增长而保持良好。然而，反应动力学发生了变化，表现为反应较慢，刺激后的下冲减少，这可能是由于血管壁僵硬等因素造成的。使用改进的 Krogh 模型对净耗氧量的估计表明，刺激过程中的 O 过冲可能是必要的，以确保更高的毛细血管 O 输送到组织，与增加的 CMRO 成比例，以维持毛细血管组织 pO。观察到 CMRO 和毛细血管 O 输送之间的耦合随年龄增长而保持不变。
