Laboratory of Molecular Neuroscience, Academy of Biology and Biotechnology, Southern Federal University, Rostov-on-Don, Russia.
Brain Inj. 2021 Mar 21;35(4):490-500. doi: 10.1080/02699052.2021.1879397. Epub 2021 Feb 1.
: In an ischemic stroke, the damage spreads from the infarction core to surrounding tissues. The present work was aimed at the search of effective neuroprotectors that restrict injury propagation. : We studied possible protective effects of inhibitors of protein kinases LIMK2 (T56-LIMKi), DYRK1A (harmine), and tryptophan hydroxylase (4-chlorophenylalanine) on infarction size and morphology of peri-infarct area after photothrombotic stroke (a model of ischemic stroke) in mouse brain. : Photothrombotic stroke was induced by laser irradiation of mouse cortex after administration of photosensitizer Bengal Rose, which does not penetrate cells and remains in blood vessels. Under light exposure, it induces vessel occlusion. Infarct volume and histological changes in the cerebral cortex were evaluated 3, 7 and 14 days after photothrombotic impact. : Harmine and 4-chlorophenylalanine did not influence infarct volume and morphology of peri-infarct area in the mouse brain cortex after photothrombotic stroke. However, LIMK2 inhibitor T56-LIMKi significantly reduced infarct volume 7 and 14 days after photothrombotic stroke. It also increased the percent of normochromic neurons and decreased the fraction of altered cortical cells (hypochromic, hyperchromic and pyknotic neurons). : T56-LIMK2i may be considered as a promising anti-stroke agent.
在缺血性中风中,损伤从梗塞核心向周围组织扩散。本工作旨在寻找限制损伤传播的有效神经保护剂。
我们研究了蛋白激酶 LIMK2(T56-LIMKi)、DYRK1A(哈尔明)和色氨酸羟化酶(4-氯苯丙氨酸)抑制剂对小鼠脑光血栓性中风(缺血性中风模型)后梗塞大小和梗塞周围区形态的可能保护作用。
光血栓性中风是通过在给予光敏剂孟加拉玫瑰后激光照射小鼠皮层诱导的,孟加拉玫瑰不能穿透细胞,留在血管中。在光暴露下,它会引起血管闭塞。在光血栓作用后 3、7 和 14 天评估梗塞体积和大脑皮层的组织学变化。
哈尔明和 4-氯苯丙氨酸对光血栓性中风后小鼠大脑皮层的梗塞体积和梗塞周围区形态没有影响。然而,LIMK2 抑制剂 T56-LIMKi 显著减少光血栓性中风后 7 天和 14 天的梗塞体积。它还增加了正常色神经元的百分比,减少了改变的皮质细胞(浅染、深染和固缩神经元)的分数。
T56-LIMK2i 可被视为一种有前途的抗中风药物。