Bhatti Mehwish, Frostig Ron D
University of California.
Res Sq. 2023 Mar 30:rs.3.rs-2698138. doi: 10.21203/rs.3.rs-2698138/v1.
We have previously demonstrated protection from impending cortical stroke is achievable by sensory stimulation of the ischemic area in an adult rat model of permanent middle cerebral artery occlusion (pMCAo). We have further demonstrated that a major underpinning mechanism that is necessary for such protection is the system of collaterals among cerebral arteries that results in reperfusion of the MCA ischemic territory. However, since such collateral flow is weak, it may be necessary but not sufficient for protection and therefore we were seeking other complementary mechanisms that contribute to sensory-based protection. We hypothesized that astrocytes-to-neuron shuttle (ANLS) is another potential underpinning mechanism that could complement collateral flow in the protection process. Supporting our hypothesis, using functional imaging, pharmacological treatments, and postmortem histology, we show that ANLS has a pivotal role in sensory-based protection of cortex and therefor serves as the other supporting mechanism underpinning the protection process.
我们先前已经证明,在成年大鼠永久性大脑中动脉闭塞(pMCAo)模型中,通过对缺血区域进行感觉刺激可以实现对即将发生的皮质中风的保护。我们进一步证明,这种保护所必需的一个主要支撑机制是脑动脉之间的侧支循环系统,该系统可导致大脑中动脉缺血区域的再灌注。然而,由于这种侧支血流较弱,它对于保护可能是必要的,但并不充分,因此我们一直在寻找有助于基于感觉的保护的其他互补机制。我们假设星形胶质细胞到神经元穿梭(ANLS)是另一种潜在的支撑机制,它可以在保护过程中补充侧支血流。支持我们的假设的是,通过功能成像、药物治疗和死后组织学研究,我们表明ANLS在基于感觉的皮质保护中起关键作用,因此是支撑保护过程的另一种支持机制。