Abstract：
Cerebral small vessel disease (CSVD) is a major cause of vascular cognitive impairment and functional loss in elderly patients. Progressive remodeling of cerebral microvessels due to arterial hypertension or other vascular risk factors, such as aging, can cause dementia or stroke. Typical imaging characteristics of CSVD include cerebral microbleeds (CMB), brain atrophy, small subcortical infarctions, white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). Nevertheless, no animal models that reflect all the different aspects of CSVD have been identified. Here, we generated a new CSVD animal model using D-galactose (D-gal) combined with cerebral hypoperfusion in spontaneously hypertensive rats (SHR), which showed all the hallmark pathological features of CSVD and was based on vascular risk factors. SHR were hypodermically injected with D-gal (400 mg/kg/d) and underwent modified microcoil bilateral common carotid artery stenosis surgery. Subsequently, neurological assessments and behavioral tests were performed, followed by vascular ultrasonography, electron microscopy, flow cytometry, and histological analyses. Our rat model showed multiple cerebrovascular pathologies, such as CMB, brain atrophy, subcortical small infarction, WMH, and EPVS, as well as the underlying causes of CSVD pathology, including oxidative stress injury, decreased cerebral blood flow, structural and functional damage to endothelial cells, increased blood-brain barrier permeability, and inflammation. The use of this animal model will help identify new therapeutic targets and subsequently aid the development and testing of novel therapeutic interventions. Main process of the study: Firstly, we screened for optimal conditions for mimicking aging by injecting D-gal into rats for 4 and 8 weeks. Subsequently, we performed modified microcoil BCAS intervention for 4 and 8 weeks in rats to screen for optimal hypoperfusion conditions. Finally, based on these results, we combined D-gal for 8 weeks and modified microcoil BCAS for 4 weeks to explore the changes in SHR.
摘要：
脑小血管病（CSVD）是老年患者血管性认知障碍和功能丧失的主要原因。由于动脉高血压或其他血管危险因素导致的脑微血管的进行性重塑，如衰老，可导致痴呆或中风。CSVD的典型影像学特征包括脑微出血(CMB),脑萎缩,小的皮质下梗塞,白质高强度（WMH），和扩大的血管周围空间（EPVS）。然而，尚未发现反映CSVD所有不同方面的动物模型.这里,我们使用D-半乳糖（D-gal）联合脑低灌注在自发性高血压大鼠（SHR）中产生了一种新的CSVD动物模型，显示了CSVD的所有标志性病理特征，并基于血管危险因素。SHR皮下注射D-gal（400mg/kg/d），并接受改良的微线圈双侧颈总动脉狭窄手术。随后，进行神经评估和行为测试，然后是血管超声检查，电子显微镜，流式细胞术,和组织学分析。我们的大鼠模型显示多种脑血管病变,例如CMB，脑萎缩,皮质下小梗死,WMH,和EPVS，以及CSVD病理的根本原因，包括氧化应激损伤，脑血流量减少,内皮细胞的结构和功能损伤，血脑屏障通透性增加，和炎症。这种动物模型的使用将有助于确定新的治疗靶标，并随后帮助开发和测试新的治疗干预措施。研究的主要过程:首先,我们通过将D-gal注射入大鼠4周和8周，筛选了模拟衰老的最佳条件。随后，我们对大鼠进行了4周和8周的改良微线圈BCAS干预,以筛选最佳的低灌注条件.最后,基于这些结果，我们联合D-gal治疗8周，改良微线圈BCAS治疗4周，探讨SHR的变化。
