Impact of NA ‐1 on Pericyte‐Driven Vasoconstriction and Its Role in No‐Reflow During Cerebral Ischemia–Reperfusion

作者：Xinxuan Yang, Jiahui Zhao, Hao Tian, Ximing Nie, Lina Zheng, Xin Liu, Zheng Wei, Yuchuan Ding, Liping Liu · 发表于：CNS Neuroscience & Therapeutics · 年份：2025 · DOI：10.1111/cns.70409 · 被引用次数：7 · 研究领域：Barrier Structure and Function Studies、Neuroscience and Neuropharmacology Research、Angiogenesis and VEGF in Cancer

ABSTRACT Background The no‐reflow phenomenon in the ischemic brain following arterial recanalization leads to poor prognosis. Previous studies suggest that the clinically proven NA‐1 drug, with disruption of PSD95 in the neuronal terminals alongside the cerebral microvasculature, may inhibit pericytic contraction of microvessels by reducing endothelin‐1 secretion. Methods A 1.5‐h tMCAO model using Balb/c mice was employed. In vivo two‐photon imaging and immunofluorescence staining were employed to assess the constriction effect of pericytes on capillaries. The impact of NR2B9c/NA‐1 administration (intravenously infused at a dose of 10 μmol/kg) on pericyte constriction was evaluated through immunofluorescent staining of brain sections. Additionally, The effect of NA‐1 on cerebral perfusion was assessed using laser speckle blood flow monitoring, whole brain slice perfusion, and high‐magnification capillary imaging. Enzyme‐linked immunosorbent Assay (ELISA) was conducted to determine changes in quantitative ONOO − and endothelin‐1 (ET‐1) content after tat‐NA‐1 administration. Lastly, microtubule‐associated protein 2 (MAP2) staining and behavioral scores were used to evaluate the effects of NA‐1 on infarct size and behavioral deficits. Results In vivo two‐photon imaging and immunofluorescence staining revealed that pericyte constriction following ischemia and recanalization resulted in a decreased diameter of capillaries, particularly at the soma and adjacent areas. Notably, capi...