Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
J Cereb Blood Flow Metab. 2024 Sep;44(9):1677-1690. doi: 10.1177/0271678X241264083. Epub 2024 Jul 25.
Although most laminin isoforms are neuroprotective in stroke, mural cell-derived laminin-α5 plays a detrimental role in an ischemia-reperfusion model. To determine whether this deleterious effect is an intrinsic feature of mural cell-derived laminin-α5 or unique to ischemic stroke, we performed loss-of-function studies using middle-aged mice with laminin-α5 deficiency in mural cells (α5-PKO) in an intracerebral hemorrhage (ICH) model. Control and α5-PKO mice exhibited comparable changes in all parameters examined, including hematoma size, neuronal death, neurological function, blood-brain barrier integrity, and reactive gliosis. These findings highlight a minimal role of mural cell-derived laminin-α5 in ICH. Together with the detrimental role of mural cell-derived laminin-α5 in ischemic stroke, these negative results in ICH model suggest that mural cell-derived laminin-α5 may exert distinct functions in different diseases.
尽管大多数层粘连蛋白同工型在中风中具有神经保护作用，但壁细胞衍生的层粘连蛋白-α5 在缺血再灌注模型中发挥有害作用。为了确定这种有害作用是壁细胞衍生的层粘连蛋白-α5 的固有特征还是仅存在于缺血性中风中，我们在脑内出血 (ICH) 模型中使用壁细胞中缺乏层粘连蛋白-α5 的中年小鼠 (α5-PKO) 进行了功能丧失研究。对照和 α5-PKO 小鼠在所有检查的参数中表现出相当的变化，包括血肿大小、神经元死亡、神经功能、血脑屏障完整性和反应性神经胶质增生。这些发现强调了壁细胞衍生的层粘连蛋白-α5 在 ICH 中的作用很小。与壁细胞衍生的层粘连蛋白-α5 在缺血性中风中的有害作用一起，ICH 模型中的这些负面结果表明壁细胞衍生的层粘连蛋白-α5 可能在不同疾病中发挥不同的功能。
