关键词: blood–brain barrier chronic injury foam cells ischemic stroke

Mesh : Animals Male Mice Female Ischemic Stroke / pathology diagnostic imaging metabolism blood Mice, Inbred C57BL Infarction, Middle Cerebral Artery / pathology Disease Models, Animal Inflammation / pathology Brain / pathology metabolism diagnostic imaging Blood-Brain Barrier / pathology metabolism Magnetic Resonance Imaging Reperfusion Injury / pathology metabolism Neurofilament Proteins

来  源:   DOI:10.14814/phy2.16118   PDF(Pubmed)

Abstract:
Stroke is a pervasive and debilitating global health concern, necessitating innovative therapeutic strategies, especially during recovery. While existing literature often focuses on acute interventions, our study addresses the uniqueness of brain tissue during wound healing, emphasizing the chronic phase following the commonly used middle cerebral artery (MCA) occlusion model. Using clinically relevant endpoints in male and female mice such as magnetic resonance imaging (MRI) and plasma neurofilament light (NFL) measurement, along with immunohistochemistry, we describe injury evolution. Our findings document significant alterations in edema, tissue remodeling, and gadolinium leakage through MRI. Plasma NFL concentration remained elevated at 30 days poststroke. Microglia responses are confined to the region adjacent to the injury, rather than continued widespread activation, and boron-dipyrromethene (BODIPY) staining demonstrated the persistent presence of foam cells within the infarct. Additional immunohistochemistry highlighted sustained B and T lymphocyte presence in the poststroke brain. These observations underscore potentially pivotal roles played by chronic inflammation brought on by the lipid-rich brain environment, and chronic blood-brain barrier dysfunction, in the development of secondary neurodegeneration. This study sheds light on the enduring consequences of ischemic stroke in the most used rodent stroke model and provides valuable insights for future research, clinical strategies, and therapeutic development.
摘要:
中风是一个普遍和衰弱的全球健康问题,需要创新的治疗策略,尤其是在恢复期间。虽然现有文献通常侧重于急性干预,我们的研究探讨了伤口愈合过程中脑组织的独特性,强调慢性期遵循常用的大脑中动脉(MCA)闭塞模型。在雄性和雌性小鼠中使用临床相关终点,例如磁共振成像(MRI)和等离子神经丝光(NFL)测量,随着免疫组织化学,我们描述了损伤的演变。我们的发现记录了水肿的显著改变,组织重塑,和钆通过核磁共振泄漏。血浆NFL浓度在中风后30天保持升高。小胶质细胞反应仅限于损伤附近的区域,而不是持续广泛的激活,和硼-二吡咯亚甲基(BODIPY)染色显示梗死灶内持续存在泡沫细胞。其他免疫组织化学强调了中风后脑中持续存在的B和T淋巴细胞。这些观察结果强调了由富含脂质的大脑环境引起的慢性炎症所发挥的潜在关键作用。和慢性血脑屏障功能障碍,在继发性神经变性的发展中。这项研究揭示了缺血性中风在最常用的啮齿动物中风模型中的持久后果,并为未来的研究提供了有价值的见解。临床策略,和治疗发展。
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