Little is known about how thalamic vascular patterns interact with small vessel diseases (SVDs) to influence affective symptoms. Here we collected 7-Telsa magnetic resonance imaging (MRI) data from 84 individuals with SVD and analyzed the influences of thalamic vascular pattern on affective symptoms, aiming to elucidate the underlying mechanisms driven by brain structure and function in the context of SVD. Subjects with a combined arterial supply by tuberothalamic and paramedian arteries to the right thalamus exhibited a lower Hamilton Anxiety scale (HAMA) score. When grouped by SVD burden, the same correlation remained in subjects with low SVD burden, whereas no difference was observed in the high SVD burden group. Interestingly, interaction effects of SVD and thalamic vascular pattern were also found affecting thalamic volume and resting-state brain activity in ventromedial prefrontal cortex (vmPFC). With moderated mediation analysis, right thalamic vascular pattern was indicated to affect anxiety through both direct (vascular pattern → HAMA score) and indirect (vascular pattern → thalamic volume → HAMA score) pathways. But high SVD burden interrupted the effects of right thalamic vascular pattern on HAMA score and thalamic volume. The finding that subjects with a combined arterial supply to the right thalamus exhibited a lower level of anxiety may suggest a novel vascular resilience for regulating anxiety. However, this vascular compensation mechanism was found to be impaired by elevated SVD burden and the disrupted inhibitory vmPFC activity caused by impaired thalamus. The findings of the present study provide a new underlying mechanism for affective disorders with SVD involved.

Gait disturbance is a manifestation of cerebral small vessel disease (CSVD). The posterolateral thalamus (PL), whose blood is mainly supplied by the P2 segment of posterior cerebral artery (P2-PCA), plays pivotal roles in gait regulation. We investigated the influence of the distance between P2-PCA and PL on gait with varying CSVD burden. 71 participants were divided into low and high CSVD burden groups. The distance from P2-PCA to PL was measured using 7 T TOF-MRA and categorized into an immediate or distant PCA-to-thalamus pattern. Functional connectivity (FC) and voxel-based morphometry were assessed to evaluate functional and structural alterations. In the low CSVD burden group, immediate PCA-to-thalamus supply strongly correlates with longer step length and higher wave phase time percent, and exhibited enhanced FCs in left supplementary motor area, right precentral cortex (PreCG.R). While in the high CSVD burden group, no association between PCA-to-thalamus pattern and gait was found, and we observed reduced FC in PreCG.R with immediate PCA-to-thalamus pattern. Higher CSVD burden was associated with decreased gray matter density in bilateral thalamus. However, no significant structural thalamic change was observed between the two types of PCA-to-thalamus patterns in all patients. Our study demonstrated patients with immediate PCA-to-thalamus supply exhibited better gait performance in low CSVD burden populations, which also correlated with enhanced FCs in motor-related cortex, indicating the beneficial effects of the immediate PCA-to-thalamus supply pattern. In the higher burden CSVD populations, the effects of PCA-to-thalamus pattern on gait are void, attributable to the CSVD-related thalamic destruction and impairment of thalamus-related FC.

This study was designed to evaluate antiplatelet effect and therapeutic effect of ginkgo diterpene lactone meglumine injection (GDLI) in acute ischemic stroke (AIS) patients. In this randomized, double-blind, placebo-controlled trial, we randomly assigned 70 inpatients within 48 hr after the onset of AIS to combination therapy with GDLI and aspirin (GDLI at a dose of 25 mg/d for 14 days plus aspirin at a dose of 100 mg/d for 90 days) or to placebo plus aspirin in a ratio of 1:1. Platelet function, the National Institute of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were evaluated. A good outcome was defined as NIHSS scores decrease >= 5 or mRS scores decrease >= 2. Results showed that arachidonic acid induced maximum platelet aggregation rate (AA-MAR) and mean platelet volume (MPV) of the GDLI-aspirin group were much lower than that of the aspirin group (p = 0.013 and p = 0.034, respectively) after the 14-day therapy. The combination of GDLI and aspirin was superior to aspirin alone, and had significant impact on the good outcome at day 90 (ORadj 7.21 [95%CI, 1.03-50.68], p = 0.047). In summary, GDLI has antiplatelet effect and can improve the prognosis of AIS patients.

Objective Cerebral small vessel disease (CSVD) is a clinical syndrome caused by pathological changes in small vessels. Anxiety is a common symptom of CSVD. Previous studies have reported the association between inflammatory factors and anxiety in other diseases, but this association in patients with CSVD remains uncovered. Our study aimed to investigate whether serum inflammatory factors correlated with anxiety in patients with CSVD. Methods A total of 245 CSVD patients confirmed using brain magnetic resonance imaging (MRI) were recruited from December 2019 to December 2021. Hamilton Anxiety Rating Scale (HAMA) was used to assess the anxiety symptoms of CSVD patients. Patients with HAMA scores ≥7 were considered to have anxiety symptoms. The serum levels of interleukin-1β (IL-1β), IL-2R, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), C-reactive protein (CRP), high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were detected. We compared levels of inflammatory factors between the anxiety and non-anxiety groups. Logistic regression analyses examined the correlation between inflammatory factors and anxiety symptoms. We further performed a gender subgroup analysis to investigate whether this association differed by gender. Results In the fully adjusted multivariate logistic regression analysis model, we found that lower levels of IL-8 were linked to a higher risk of anxiety symptoms. Moreover, higher levels of SAA were linked to a lower risk of anxiety symptoms. Our study identified sex-specific effects, and the correlation between IL-8 and anxiety symptoms remained significant among males, while the correlation between SAA and anxiety symptoms remained significant among females. Conclusions In this study, we found a suggestive association between IL-8, SAA, and anxiety symptoms in CSVD participants. Furthermore, IL-8 and SAA may have a sex-specific relationship with anxiety symptoms.

Background The association between perivascular space (PVS) and white matter hyperintensity (WMH) has been unclear. Normal-appearing white matter (NAWM) around WMH is also found correlated with the development of focal WMH. This study aims to investigate the topological connections among PVS, deep WMH (dWMH) and NAWM around WMH using 7 Tesla (7T) MRI. Methods Thirty-two patients with non-confluent WMHs and 16 subjects without WMHs were recruited from our department and clinic. We compared the PVS burden between patients with and without WMHs using a 5-point scale. Then, the dilatation and the number of PVS within a radius of 1 cm around each dWMH were compared with those of a reference site (without WMH) in the contralateral hemisphere. In this study, we define NAWM as an area within the radius of 1 cm around each dWMH. Furthermore, we assessed the spatial relationship between dWMH and PVS. Results Higher PVS scores in the centrum semiovale were found in patients with >5 dWMHs (median 3) than subjects without dWMH (median 2, p = 0.014). We found there was a greater dilatation and a higher number of PVS in NAWM around dWMH than at the reference sites (p<0.001, p<0.001). In addition, 79.59% of the dWMHs were spatially connected with PVS. Conclusion dWMH, NAWM surrounding WMH and MRI-visible PVS are spatially correlated in the early stage of cerebral small vessel disease. Future study of WMH and NAWM should not overlook MRI-visible PVS.

Emerging evidence supports that the gut microbiome, reconsidered as a new organ in the human body, can not only affect the local gut, but also communicate with the brain via multiple pathways related to neuroendocrine, immune, and neural pathways, thereby proposing the new concept of the microbiome-gut-brain (MGB) axis. Recently, the role of short-chain fatty acids (SCFAs), which are the main anaerobic fermented metabolites of the gut microbiota in the MGB axis, has garnered significant attention. SCFAs are involved in a broad range of central neurological diseases, including neurodegenerative diseases, cerebral vascular diseases, epilepsy, neuroimmune inflammatory diseases, and mood disorders. However, the underlying mechanism of SCFA-related distant organ crosstalk is yet to be elucidated. Herein, we summarize current knowledge regarding interactions between SCFAs and the MGB axis, as well as their protective effects against central neurological diseases.

Emerging evidence supports that the gut microbiome, reconsidered as a new organ in the human body, can not only affect the local gut, but also communicate with the brain via multiple pathways related to neuroendocrine, immune, and neural pathways, thereby proposing the new concept of the microbiome-gut-brain (MGB) axis. Recently, the role of short-chain fatty acids (SCFAs), which are the main anaerobic fermented metabolites of the gut microbiota in the MGB axis, has garnered significant attention. SCFAs are involved in a broad range of central neurological diseases, including neurodegenerative diseases, cerebral vascular diseases, epilepsy, neuroimmune inflammatory diseases, and mood disorders. However, the underlying mechanism of SCFA-related distant organ crosstalk is yet to be elucidated. Herein, we summarize current knowledge regarding interactions between SCFAs and the MGB axis, as well as their protective effects against central neurological diseases.

Background: Cerebral small vessel disease (CSVD) is a group of clinical syndromes covering all pathological processes of small vessels in the brain, which can cause stroke and serious dementia. However, as the pathogenesis of CSVD is not clear, so the treatment is limited. Endothelial cell dysfunction is earlier than clinical symptoms, such as hypertension and leukosis. Therefore, the treatment of endothelial cells is expected to be a new breakthrough. Quercetin, a flavonoid present in a variety of plants, has the function of anti-inflammation and anti-oxidation. This study aimed to investigate the protective effect of quercetin on endothelial cell injury and provide a basic theory for subsequent application in the clinic. Methods: Human brain microvascular endothelial cells (HBMECs) were cultured in vitro, and the injury model of endothelial cells was established by hypoxia and reoxygenation (H/R). The protective effects of quercetin on HBMECs were studied from the perspectives of cell viability, cell migration, angiogenesis and apoptosis. In order to further study the mechanism of quercetin, oxidative stress and endoplasmic reticulum stress were analyzed. What’s more, blood-brain barrier (BBB) integrity was also studied. Results: Quercetin can promote the viability, migration and angiogenesis of HBMECs, and inhibit the apoptosis. In addition, quercetin can also activate Keap1/Nrf2 signaling pathway, reduce ATF6/GRP78 protein expression. Further study showed that quercetin could increase the expression of Claudin-5 and Zonula occludens-1. Conclusions: Our experiments show that quercetin can protect HBMECs from H/R, which contains promoting cell proliferation, cell migration and angiogenesis, reducing mitochondrial membrane potential damage and inhibiting cell apoptosis. This may be related to its antioxidation and inhibition of endoplasmic reticulum stress. At the same time, quercetin can increase the level of BBB connexin, suggesting that quercetin can maintain BBB integrity.

Diabetes exacerbates brain damage in cerebral ischemic stroke. Our previous study has demonstrated that after cerebral ischemia, type 2 diabetes rats displayed worse neurological outcomes, larger cerebral infarction and severer blood-brain barrier disruption. However, our knowledge of the mechanisms of how diabetes impacts the cerebrovascular repair process is limited. This study was aimed to characterize structural alterations and potential mechanisms in brain microvessels before and after ischemic stroke in type 2 diabetic rats treated with high-fat diet and streptozotocin (HFD/STZ). Furtherly, we tested our hypothesis that dysregulated intercellular Jagged1-Notch1 signaling was involved in the dysfunctional cerebral neovascularization both before and after ischemic stroke in HFD/STZ rats. In our study, we found increased yet dysfunctional neovascularization with activated Jagged1-Notch1 signaling in the cerebrovasculature before cerebral ischemia in HFD/STZ rats compared with non-diabetic rats. Furthermore, we observed delayed angiogenesis as well as suppressed Jagged1-Notch1 signaling after ischemic stroke. Our results elucidate the potential mechanisms underlying diabetes-related cerebral microvasculature dysfunction after ischemic stroke.

目的 探讨以双侧丘脑病变导致认知功能减退起病的硬脑膜动静脉瘘(dAVFs)的临床、影像学特点和鉴别诊断、诊治方法.方法 分析1例dAVFs患者的临床资料,结合国内外文献进行分析讨论.结果 本例患者临床表现为进展性的认知功能减退,MRI T2相见双侧丘脑高信号,经DSA确诊为dAVFs,行血管内栓塞治疗后症状基本恢复.本研究系统检索了具有相似影像学表现的dAVFs相关文献报道30例,其临床表现以记忆力减退最为显著,部分伴有精神行为异常,经介入治疗或手术治疗大多预后良好.结论 以双侧丘脑受累表现为认知功能减退的dAVFs报道较少,临床中出现类似病例应考虑到该诊断.

Diabetic patients manifest with more severe neurological deficits than non-diabetes after ischemic stroke. It has been shown that hypothermia has neuroprotective effects on cerebral ischemia, but whether it is effective for cerebral ischemia in diabetic patients remains unknown. The aim of this study was to investigate whether hypothermia can alleviate cerebral ischemic injury in diabetic rats and the regulation of autophagy and pyroptosis of the treatment. We introduced permanent middle cerebral artery occlusion (pMCAO) in a model of type 2 diabetic rats prepared by high-fat diet combined with intraperitoneal injection of STZ in vivo and mimicked cerebral ischemia with diabetes by employing high glucose stimulation and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Moreover, 3-methyladenine and bafilomycin A1 were used to evaluate the association between autophagy and pyroptosis in vitro. Our results showed that diabetes aggravated neurological deficits, increased the volume of cerebral infarction and brain edema as well as the blood brain barrier permeability after cerebral ischemia, which were alleviated by mild hypothermia. Compared with the pMCAO model in non-diabetic rats and OGD/R model without high glucose stimulation in vitro, the expression of P62, NOD-like receptor protein 3 (NLRP3), cleaved caspase-1 and Gasdermin-N increased and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ decreased in the pMCAO model in diabetic rats and OGD/R model with high glucose stimulation, which could be reversed by mild hypothermia. In conclusion, mild hypothermia alleviated diabetes aggravated cerebral ischemic injury via activating autophagy and inhibiting pyroptosis.

ABSTRACT Aim To explore the effect and mechanism of mild hypothermia on cell apoptosis in diabetic rats with cerebral infarction. Methods Male healthy SD rats were divided into a diabetic group ( n=42 ) and a non-diabetic group ( n =14 ) randomly. Type 2 diabetes was induced by high-fat diet combined with STZ. The rats were divided into a diabetic cerebral ischemic normothermic group ( DNT group, n=14) ,a diabetic cerebral ischemic hypothermia group ( DHT group) ( n=14), a diabetic sham group( DS group, n=14) and a non-diabetic cerebral ischemic normothermic group ( NNT group, n=14) randomly after 2 weeks of successful modeling. The hypothermia group was treated with hypothermia for 6 hours starting from 2 hours after pMCAO. The neurological deficit in each group was tested at several time points after cerebral ischemia, and the level of apoptosis, the expression of matrix metalloprotein 9(MMP-9) were detected in the ischemic penumbra in each group. Results ①Compared with the NNT group, the neurological function score was lower in DNT group after cerebral ischemia( P<0.05) , and the level of apoptosis was higher in DNT group(P<0.05). Meanwhile, the expression of MMP-9 and cleaved caspase-3 was increased in DNT group ( P <0.05 ) . The gene expression of Bcl-2 was decreased and Bim was increased( P<0.05) . ②Compared with the DNT group, the neurological function score was higher in DHT group after cerebral ischemia( P<0.05) , and the level of apoptosis was lower in DHT group( P<0.05) . At the meantime, the expression of MMP-9 and cleaved caspase-3 was reduced in DHT group( P<0.05) . The gane expression of Bcl-2 was increased and Bim was decreased ( P <0.05) . Conclusion Diabetes aggravated the neurological deficit in rats with cerebral infarction, while mild hypothermia alleviated neurological deficit in rats with diabetic cerebral infarction. The underlying neuroprotective mechanisms of mild hypothermia may be related to inhibiting apoptosis in ischemic penumbra by reducing the damage of the blood-brain barrier.

Although recent studies have shown that mild hypothermia has neuroprotective effects on intracerebral hemorrhage (ICH), the therapeutic time window of the therapy and the role of autophagy as a potential neuroprotective mechanism remain unclear. This study was aimed to investigate the appropriate time window of mild hypothermia and the regulation of autophagy during the treatment in a rat model of autologous blood-injected ICH injury. The rats were divided into Sham, normothermic (NT) and hypothermic (HT) groups. HT groups received mild hypothermia (33 degrees C-35 degrees C) for 48 h starting from 3 h (HT3), 6 h (HT6), and 12 h (HT12) respectively after ICH. The neurological function, brain edema, blood brain barrier (BBB) permeability and volume of tissue loss were tested. The expression of metrix metalloproteinase 9 (MMP-9) and tight junction (TJ) protein including Occludin and Claudin-5 around the hematoma were detected by Western blot. Moreover, autophagy after ICH was detected by the ratio of LC3B-11/I, and the expression of Beclin-1 and p62, while apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dURP nick end labelling (TUNEL) staining and expression of Bcl-2, Bim, cleaved Caspase-3. Compared with NT group, neurological deficit, brain edema and BBB permeability were attenuated in HT6 and HT12 groups, but not in HT3 group, while volume of tissue loss was reduced only in HT12 group. The expression of MMP-9 and the degradation of Occludin and Claudin-5 were suppressed only in HT6 and HT12 groups, especially in the latter one. Moreover, neuronal autophagy and apoptosis induced by ICH were downregulated in HT12 group. The results suggested that mild hypothermia initiated at 6 h or 12 h post-injury was neuroprotective in ICH model of rats, especially at 12 h post injury, via suppression of autophagy upregulated by ICH. (C) 2018 Elsevier B.V. All rights reserved.

Hyperhomocysteinemia, a risk factor for vascular disease, is associated with metabolic syndrome. Our study was aimed at exploring the effect of long-term hyperhomocysteinemia with metabolic disturbances on vascular remodeling. We also studied oxidative stress and expression of PPARγ in the coronary arteriole as a possible mechanism underlying vascular remodeling. Rats were treated with standard rodent chow (Control) or diet enriched in methionine (Met) for 48 weeks. Plasma homocysteine, blood glucose, serum lipids, malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels were measured. Coronary arteriolar and carotid arterial remodeling was assessed by histomorphometric techniques and the expression of PPARγ in vessel wall was investigated. In Met group, an increase in the level of fasting blood glucose, serum triglyceride, total cholesterol, MDA, and NO, a decline in the serum SOD level, and increased collagen deposition in coronary and carotid arteries were found. Moreover, we detected decreased expression of PPARγ in the coronary arterioles in Met group. In summary, our study revealed metabolic disturbances in this model of long-term hyperhomocysteinemia together with vascular remodeling and suggested that impaired oxidative stress, endothelium dysfunction, and decreased PPARγ expression in the vessel wall could be underlying mechanisms.

目的 探讨4-苯基丁酸(PBA)对大鼠脑出血(ICH)后脑水肿的作用及机制.方法 健康雄性SD大鼠,随机分为ICH组、PBA 100 mg·kg-1组、PBA 300 mg·kg-1组(均n=15)和假手术组(n=9),采用自体血脑内立体定向注射法建立大鼠ICH模型,不同剂量组PBA干预组于术后即刻每24 h腹腔注射相应剂量的PBA,评价术后不同时间点各组大鼠神经功能评分.各组大鼠均于术后72 h处死,干湿重法检测脑水肿情况,伊文思蓝法检测血脑屏障通透性变化,同时Western blot法检测血肿周围脑组织中基质金属蛋白酶9(MMP-9)表达的变化.结果 PBA 300 mg·kg-1组各时间点神经功能缺损显著低于ICH组(P＜0.05).ICH后72 h,PBA 100 mg·kg-1组、PBA 300 mg·kg-1组脑组织含水量和伊文思蓝含量显著低于ICH组(P＜0.05);血肿周围组织中MMP-9表达也显著低于ICH组(P＜0.05).结论 PBA能够改善大鼠ICH模型的神经功能缺损,减轻ICH后水肿和改善血脑屏障通透性,抑制血肿周围脑组织中MMP-9的表达是可能作用机制.

Background and purpose: Mild hypothermia has been proved to reduce global and focal cerebral ischemic injury in rodents by preventing cellular apoptosis through several pathways. However, whether hypothermia will be beneficial for intracerebral hemorrhage (ICH) and its underlying mechanisms haven't reached a consensus. It has been implicated that endoplasmic reticulum (ER) stress plays a role in the secondary injury after ICH in rats. In this study, we aimed to investigate whether mild hypothermia would attenuate ICH induced neuronal injury via regulating ER stress.Methods: The model of ICH was induced by injecting autologous blood (120 mu l) into the rat striatum. Rats were divided into sham, normothermic (NT) and hypothermic (HT) groups. HT group were subjected to mild hypothermia (33 degrees C-35 degrees C) for 2 days starting from 6 h after ICH. Neurological deficits were evaluated. The ER stress related proteins (GRP78, CHOP and p-eIF2 alpha) and the apoptosis associated indicators (cleaved caspase3, Bcl-2 and Bim) around hematoma were assessed by western blot, qRT-PCR(quantificational real-time polymerase chain reaction), immunofluorescence and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) assay.Results: Neurological deficits following ICH were reduced in HT group compared to NT group. Protein levels of GRP78, CHOP and p-eIF2a significantly increased after ICH in both NT and HT group compared to sham group, which was consistent with the trend of cleaved-caspase3 at protein level, and Bim, Bcl-2 at gene level. In comparison to NT group, GRP78, CHOP, p-eIF2 alpha, cleaved caspase-3 and Bim all decreased, while Bcl-2 increased in HT group. Additionally, apoptotic cells detected by TUNEL staining significantly decreased in the HT group.Conclusion: Mild hypothermia could attenuate ICH caused neuron injury by decreasing ER response induced neuron apoptosis. (C) 2016 Published by Elsevier Ireland Ltd.