Conti Emilia, Minetti Antea, Turrini Lapo, Carlini Noemi, Sarti Cristina, Gori Anna Maria, Sticchi Elena, Giusti Betti, Spalletti Cristina, Baldereschi Marzia, Allegra Mascaro Anna Letizia, Pavone Francesco Saverio
National Institute of Optics, National Research Council, Sesto Fiorentino, Italy.
European Laboratory for Non-Linear Spectroscopy (LENS), Sesto Fiorentino, Italy.
Commun Biol. 2025 Jul 28;8(1):1117. doi: 10.1038/s42003-025-08398-w.
Ischemic stroke caused by the abrupt interruption of blood flow is one of the leading causes of death and disability worldwide. Despite expanding reperfusion treatment indications, a significant proportion of patients (54.5%) experiences poor outcomes, regardless of successful recanalization, emphasizing the need for clinically relevant preclinical stroke models to better understand the mechanisms associated with effective reperfusion. Here, we develop and characterize a novel mouse model of light-induced recanalization following the photothrombotic occlusion of the distal branch of the middle cerebral artery (MCA). The recanalization provides a meaningful reduction of the infarct volume compared to non-recanalized mice. Moreover, the generalized motor impairment is less severe, as measured by the Neuro Deficit score. Ex vivo investigation highlights that light-mediated recanalization mitigates astrocyte complexity in the periinfarct cortex of recanalized mice. Moreover, light-induced recanalization reduces cerebral edema occurrence. Finally, the investigation of circulating biomarkers shows that our model of occlusion and recanalization of the MCA recapitulates the neuroinflammatory cascade of the acute phase of ischemic stroke.
由血流突然中断引起的缺血性中风是全球范围内死亡和残疾的主要原因之一。尽管再灌注治疗适应症不断扩大,但仍有相当比例的患者(54.5%)预后不佳,无论再通是否成功,这凸显了需要具有临床相关性的临床前中风模型,以更好地了解与有效再灌注相关的机制。在此,我们开发并表征了一种新型小鼠模型,该模型在大脑中动脉(MCA)远端分支光血栓闭塞后实现光诱导再通。与未再通的小鼠相比,再通使梗死体积有意义地减小。此外,通过神经功能缺损评分测量,全身运动障碍较轻。体外研究表明,光介导的再通减轻了再通小鼠梗死周围皮质中星形胶质细胞的复杂性。此外,光诱导的再通减少了脑水肿的发生。最后,对循环生物标志物的研究表明,我们的MCA闭塞和再通模型概括了缺血性中风急性期的神经炎症级联反应。