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星形胶质细胞-神经元乳酸穿梭在永久性大脑中动脉闭塞大鼠模型中的感觉神经保护中起关键作用。

Astrocyte-neuron lactate shuttle plays a pivotal role in sensory-based neuroprotection in a rat model of permanent middle cerebral artery occlusion.

机构信息

Department of Neurobiology and Behavior, School of Biological Sciences, University of California, Irvine, Irvine, CA, USA.

Department of Biomedical Engineering, School of Engineering, University of California, Irvine, Irvine, CA, USA.

出版信息

Sci Rep. 2023 Aug 7;13(1):12799. doi: 10.1038/s41598-023-39574-9.

DOI:10.1038/s41598-023-39574-9
PMID:37550353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10406860/
Abstract

We have previously demonstrated protection from impending cortical ischemic 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 sought other complementary mechanisms that contribute to sensory-based protection. We hypothesized that astrocytes-neuron lactate shuttle (ANLS) activation could be another potential underpinning mechanism that complements collateral flow in the protection process. Supporting our hypothesis, using functional imaging, pharmacological treatments, and postmortem histology, we showed that ANLS played a pivotal role in sensory stimulation-based protection of cortex and therefore serves as the other supporting mechanism underpinning the protection process.

摘要

我们之前已经证明,通过对永久性大脑中动脉闭塞(pMCAo)成年大鼠模型中缺血区域的感觉刺激,可以实现对即将发生的皮质性缺血性中风的保护。我们进一步证明,对于这种保护来说,一个必要的主要基础机制是脑动脉之间的侧支循环系统,这导致 MCA 缺血区域的再灌注。然而,由于这种侧支血流较弱,它可能是必要的,但不足以实现保护,因此我们寻求其他有助于基于感觉的保护的补充机制。我们假设星形胶质细胞-神经元乳酸穿梭(ANLS)的激活可能是补充保护过程中侧支血流的另一个潜在基础机制。通过功能成像、药物治疗和死后组织学,我们的研究结果支持了我们的假设,表明 ANLS 在感觉刺激基础的皮质保护中起着关键作用,因此是保护过程的另一个支持机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/750651242dbc/41598_2023_39574_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/e50dceae3d2d/41598_2023_39574_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/c4ca01199b75/41598_2023_39574_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/ab0385d6232b/41598_2023_39574_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/41c4c075d983/41598_2023_39574_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/6c2d63e6f658/41598_2023_39574_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/230d9928ed15/41598_2023_39574_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/4b19b296f30b/41598_2023_39574_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/750651242dbc/41598_2023_39574_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/e50dceae3d2d/41598_2023_39574_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/c4ca01199b75/41598_2023_39574_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/ab0385d6232b/41598_2023_39574_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/41c4c075d983/41598_2023_39574_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/6c2d63e6f658/41598_2023_39574_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/230d9928ed15/41598_2023_39574_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/4b19b296f30b/41598_2023_39574_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a6/10406860/750651242dbc/41598_2023_39574_Fig8_HTML.jpg

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