Cerebral small vessel disease (CSVD) encompasses a group of progressive disorders involving the small vessels of the brain with complex etiologies. Inflammation plays a pivotal role in both the onset and progression of CSVD. In age-related CSVD, chronic inflammation can exacerbate brain tissue damage by impairing endothelial function and disrupting the blood-brain barrier. In contrast, in inflammatory CSVD subtypes driven primarily by immune dysregulation, inflammation itself constitutes the core pathogenic mechanism. These subtypes present with diverse clinical manifestations, posing significant challenges for diagnosis and treatment. A deeper understanding of the inflammatory mechanisms involved in CSVD and the unresolved issues in this field may provide new avenues for personalized interventions and improved prognosis.
Stroke with hereditary cerebral small vessel diseases is a rare disease. Its clinical manifestations include early-onset ischemic lacunar or hemorrhagic stroke with high disability. Its typical imaging markers include lacunes, white matter hyperintensities, microbleeds, intracerebral hemorrhages located in deep or lobe of brain, crotical microinfarcts, and enlarged perivascular spaces. As the clinical and neuroimaging signs and symptoms of hereditary cerebral small vessel diseases often overlap with sporadic cerebral small vessel diseases, it is hard to diagnose. This article summarizes the clinical features, importance of obtaining valuable family history, genetic diagnosis, and management of stroke with hereditary cerebral small vessel disease to improve its accuracy diagnosis.
Objective To explore the correlations of serum levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and their ratios, with the severity of white matter hyperintensities (WMH) in patients with cerebral small vessel disease (CSVD). Methods This prospective study included patients with CSVD who were treated at Zhongshan Hospital, Xiamen University between January 2022 and February 2024. Qualitative and quantitative analyses of WMH were performed using the Fazekas scale and lesion prediction algorithm. Biomarkers such as MMP-2, MMP-9, and TIMP-1 were measured to explore their correlations with the severity of WMH. Results A total of 144 patients with CSVD were included in this study, comprising 63 males and 81 females, with an average age of (67.60±8.73) years. There were 83 (57.6%), 41 (28.5%), and 20 (13.9%) patients were categorized as Fazekas grade 1, 2, and 3 for WMH, respectively, with an median total WMH volume of 4.31 mL. Multinomial logistic regression analysis for Fazekas grade (grade 1 as the reference level) showed that MMP-2 [grade 2: odds ratio (OR)=1.059, 95% confidence interval (CI) (1.016, 1.105); grade 3: OR=1.463, 95%CI (1.124, 1.905)], TIMP-1 [grade 2: OR=1.019, 95%CI (1.006, 1.032); grade 3: OR=1.048, 95%CI (1.008, 1.090)], and MMP-9/TIMP-1 [grade 3: OR=2.650, 95%CI (1.393, 5.039)] were independently associated with Fazekas grade (P<0.05). Multinomial logistic regression analysis for the quartile group of total WMH volume (group Q1 as the reference level) showed that MMP-2 [group Q2: OR=1.160, 95%CI (1.021, 1.318); group Q3: OR=1.238, 95%CI (1.086, 1.412); group Q4: OR=1.313, 95%CI (1.140, 1.512)] and TIMP-1 [group Q2: OR=1.095, 95%CI (1.054, 1.138); group Q3: OR=1.084, 95%CI (1.045, 1.125); group Q4: OR=1.102, 95%CI (1.057, 1.149)] were independently associated with the quartile group of total WMH volume (P<0.05). Conclusions Serum levels of MMP-2 and TIMP-1 demonstrate significant independent associations with both the Fazekas grade and the total volume of WMH in patients with CSVD. These correlations underscore the potential utility of MMP-2 and TIMP-1 as critical biomarkers for assessing the severity of WMH in CSVD, highlighting their prospective roles in clinical diagnostics and therapeutic monitoring.
Objective To study the effect of silencing the NOD-like receptor family, pyrin domain containing protein 3 (NLRP3) gene on the production of inflammatory factors induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) in rat brain microvascular endothelial cells (BMECs), and whether NLRP3 inflammasome signaling pathway plays a role in the BMEC model of cerebral small vessel disease induced by proinflammatory agents. Methods BMECs from male Wistar rats were extracted in vitro and the morphology and purity of endothelial cells were identified. BMECs in normal culture were divided into blank control group and LPS+ATP group. The expression levels of NLRP3 inflammasome and downstream inflammatory factor Caspase-1 were detected by Western blot and real-time polymerase chain reaction, and compared by student’s t test between the two groups. Small interfering RNA (siRNA) was used to silence the specific gene NLRP3 in BMECs. After transfection of siRNA NLRP3 and siRNA plasmid negative control into BMECs, the transfected cells were divided into four groups, namely, siNC group (non silenced target gene), siNLRP3 group (silenced target gene), siNC+LPS+ATP group (non silenced target gene and added proinflammatory agents) and siNLRP3+LPS+ATP group (silenced target gene and added proinflammatory agents). The expression levels of NLRP3 and Caspase-1 were detected by Western blot and real-time polymerase chain reaction, and analyzed by analysis of variance for 2-factor factorial design. Results The microvascular segments of rat BMECs were “beaded” after 24 h of isolation and culture; after 48 h, “island” cell clusters were formed; after 72 h, “paving stone” like monolayer cells adhered to the wall and grew. After that, the cells gradually became dense and reached the convergence degree of 80%. The positive rate of BMECs detected by immunofluorescence staining was 96%. In the normally cultured cells, the protein and mRNA expression levels of NLRP3 and Caspase-1 in the LPS+ATP group were higher than those in the blank control group (P<0.05). In the RNA interference cultured cells, the protein and mRNA expression levels of NLRP3 and Caspase-1 in the siNLRP3 group were lower than those in the siNC group, and those expression levels in the siNLRP3+LPS+ATP group were lower than those in the siNC+LPS+ATP group (P<0.05); the protein and mRNA expression levels of NLRP3 and Caspase-1 in the siNC+LPS+ATP group were higher than those in the siNC group, and those expression levels in the siNLRP3+LPS+ATP group were higher than those in the siNLRP3 group (P<0.05). Plasmid transfection and proinflammatory agents intervention had statistically significant interaction effect on the mRNA expression of NLRP3 and Caspase-1 (P<0.05). Conclusions LPS and ATP can promote the release of NLRP3 and Caspase-1 in BMECs. Silencing NLRP3 gene expression can reduce the induction of proinflammatory agents. NLRP3 inflammasome signaling pathway may play a role in the cerebral small vessel disease cell model of rat BMECs induced by proinflammatory agents.
OBJECTIVE To investigate the clinical result in repair of soft tissue defect with combined skin flap vascularized by pedicle on the one end and vascular anastomosis on the other end. METHODS From October 1990 to August 1995, 5 cases with soft tissue defect at the extremities and 1 cases with sacral bed sore were repaired by the combined skin flaps transfer, ranged from 15 cm x 30 cm to 16 cm x 70 cm in defect, among them, 5 cases with myocutaneous flap and 1 case with skin flap, and the size of the combined skin flaps was 15 cm x 40 cm to 12 cm x 80 cm. RESULTS All the flaps were survived with satisfactory effect. Followed up 3 to 6 years, there was no obvious complication. CONCLUSION Transfer of combined skin flaps vascularized by pedicle and vascular anastomosis is suitable to repair the soft tissue defect, especially in large area defect.
Ischemic lesions, lacunar infarcts and leukoaraiosis on head CT or MRI are commonly detected in patients with non-specific symptoms such as dizziness and headache or people undergoing healthy physical examinations. Although these imaging findings are mostly related to vascular disease, especially cerebral small vessel disease, it does not mean that long-term use of antiplatelet drugs and statins are required. On the basis of literature review and clinical experiences, the article points out that the treatment methods for such manifestations include determining whether these lesions are vascular lesions, searching for risk factors or causes such as aging, hypertension, diabetes mellitus, vascular stenosis, and psychological factors, and taking strategies for the corresponding prevention and management, provides a reference for the appropriate diagnosis and treatment of these imaging manifestations in clinical practice.
Cerebral small vessel disease refers to a group of pathological processes, neuroimaging features, and clinical symptoms, with various etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain. The onset of cerebral small vessel disease can be insidious. It has various symptoms, some of which can attack acutely. Acute cerebral small vessel disease is characterized by lacunar stroke and brain parenchymal hemorrhage. The latter mainly includes hypertensive hemorrhage and cerebral amyloid angiopathy. This article summarizes the research advances of acute cerebral small vessel disease from the aspects of pathogenesis, clinical manifestations, neuroimaging features, and treatment methods, discussing characteristics and clinical challenges.
The formation of an arteriovenous fistual for dialysis by routine interrupted sutures anastomosing the vein and artery is difficult to perform and time-consuming. A new method, telescopic adhesive anastomosis was studied and applied in 10 hemodialysis patients, who were in need of an arteriovenous fistula. The external diameter of the vessels anastomosed was 2.40 +/- 0.20 mm (radial artery) or 2.40 +/- 0.35 mm (cephalic vein). After thorough debridement of the vascular ends, the arterial end was put in the venous lumen. In order to fix the telescopic vessels, two stitches were applied 180 degrees apart from each other and tied. Each stitch was inserted from vein (penetrating the whole wall) to artery (just through the adventitia and partial thickness of the media vasorum). The distance from the stitch to the edge of the vein was 0.5 mm, and that of the artery was approximated to the external diameter of the vessle. The medical adhesive was then applied for sealing the anastomotic adventitia. Ten seconds were given for the solidification of the adhesive. The patients were followed up for 8 months. The patency rate was 100%, and the rate of blood flow was more than 300 ml/min (measured by ultrasonography). It was shown that this method could be managed easily and quickly, and the so-formed fistula would fulfill the need of hemodialysis.