PLoS One
·
2015
·Vol. 10
·期 10
·e0140560
·
IF 3.234
Paul Kyu Han,Jeffrey W. Barker,Ki Hwan Kim,Seung Hong Choi,Kyongtae Ty Bae,Sung-Hong Park
The recent blood flow and magnetization transfer (MT) technique termed alternate ascending/descending directional navigation (ALADDIN) achieves the contrast using interslice blood flow and MT effects with no separate preparation RF pulse, thereby potentially overcoming limitations of conventional methods. In this study, we examined the signal characteristics of ALADDIN as a simultaneous blood flow and MT imaging strategy, by comparing it with pseudo-continuous ASL (pCASL) and conventional MT asymmetry (MTA) methods, all of which had the same bSSFP readout. Bloch-equation simulations and experiments showed ALADDIN perfusion signals increased with flip angle, whereas MTA signals peaked at flip angle around 45°−60°. ALADDIN provided signals comparable to those of pCASL and conventional MTA methods emulating the first, second, and third prior slices of ALADDIN under the same scan conditions, suggesting ALADDIN signals to be superposition of signals from multiple labeling planes. The quantitative cerebral blood flow signals from a modified continuous ASL model overestimated the perfusion signals compared to those measured with a pulsed ASL method. Simultaneous mapping of blood flow, MTA, and MT ratio in the whole brain is feasible with ALADDIN within a clinically reasonable time, which can potentially help diagnosis of various diseases.
研究领域:
医学影像
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神经影像
·
磁共振成像 (MRI)
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生物医学工程
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DOI
PubMed
高影响因子
Progress in Natural Science-Materials International
·
2024
·
IF 4.8
Qinli Ye,Jinhui Lin,Guoxiang Wang,Shuwen Zeng,Tao Jiang,Xiang Gao,Muhammad Danang Birowosuto,Wei Xiong,Chenjie Gu
Infrared thermography technology is a noninvasiveness and real-time imaging method, it has attracted enormous attentions for blood flow imaging. However, the implementation of infrared thermography technology is still limited by the poor imaging quality caused by the low temperature discrimination between the target blood vessel and background. Herein, we reported a flexible and low-cost MXene based photothermal microheater for enhancing the infrared imaging of blood flow. In the experiment, MXene films with specific thickness was prepared by vacuum filtering different concentrations of MXene colloidal solutions. Thereafter, the microheaters were fabricated by assembling the MXene films on the PU tape/PDMS substrate, and then sealed with another layer of pure PDMS film on the top of MXene film. The photothermal performance of the microheaters were evaluated by using an 808-nm laser as the exciting source. Experimental results show that the optimal microheater (MXene content: 17.5 mg) can reach a safe temperature of 41.5 °C with 43.9 s under the light irradiation of 100 mW·cm −2 . Moreover, it can be stabilized at the equilibrium temperate for over 25 min. Finally, the above optimal microheater was used to accurately heat the simulated blood vessel. It shows that temperature difference of 3.3 °C can be induced between the heated blood vessel and environment. As a result, it significantly enhances the quality of the infrared imaging of the blood flow in the simulated vascular network.
研究领域:
生物医学工程
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材料科学
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医学影像学
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产品关联
DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2018
·Vol. 32
·期 6
·e4210
·
IF 1.688
Weiguo Liao,Xiaojie Huang,Yongxin Yin,Bin Liu,Runzhi Zhu
Tetramethylpyrazine (TMP) has been widely used in the treatment of ischemic cerebrovascular disease. However, the mechanism of TMP and how to increase its bioavailability need to be further explored. In our study, an in vivo microdialysis sampling technique coupled with ultra-performance liquid chromatography–mass spectrometry method was developed to investigate the pharmacokinetic properties of TMP and its interaction with different doses of borneol (BO) in rats. Linearity of TMP in brain and blood dialysates exhibited good linear relationships over the concentration range of 0.991–555.14 ng/mL. The specificity, linearity, accuracy, precision, matrix effect and stability were within acceptable ranges. The results demonstrated that BO had a marked impact on the pharmacokinetic properties of TMP. After co-administration, the areas under the concentration–time curve (AUC) of TMP in brain and blood were significantly increased. Meanwhile, the peak concentration of TMP in brain was also enhanced. The AUC Brain /AUC Blood of TMP, increased from 44% to 56 and 60.8% after co-administration with BO (15 and 30 mg/kg). The pharmacodynamic results showed that TMP co-administration with BO enhanced the cerebral blood flow during the period of ischemia and reduced the infarct volume. Overall, it might be an effective way to treat stroke to use TMP co-administered with BO.
研究领域:
药理学
·
神经科学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
·
2024
·
IF 4.6
Jing Qiu,Yi-Han Wang,Xiu-Ming Wang,Hui-Sheng Chen
The pericytes (PCs) surrounding capillaries are vital regulators of capillary constriction. Persistent PC contraction results in the increased capillary constriction, therefore leading to the impaired cerebral blood flow (CBF) recovery after reperfusion and worsening the clinical outcomes in stroke patients. However, the potential determinants of PC functions during ischemia/reperfusion are poorly understood. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit Delta (PIK3CD/PI3Kδ) is a crucial factor involved with neuronflammation during ischemic stroke. PI3Kδ has shown the expression in PCs, while its effect on PC functions has not been explored yet. In this study, a rodent ischemia/reperfusion model was established in C57BL/6 mice via transient middle cerebral artery occlusion and reperfusion (MCAO/R). The PI3Kδ expression in ischemic penumbra was remarkably upregulated following MCAO/R induction. PI3Kδ inhibitor CAL-101 improved the CBF recovery, ischemic brain injury, and suppressed capillary constriction in MCAO/R mice. Besides, the production of tumor necrosis factor alpha (TNF-α), an inducer for tissue injury, and the expression of transient receptor potential vanilloid type 2 (TRPV2), a channel protein permitting calcium (Ca 2+ ) uptake, were significantly reduced in ischemic penumbra after CAL-101 treatment. In vitro, oxygen-glucose deprivation and reoxygenation (OGD/R) enhanced the expression of PI3Kδ and TRPV2 in primary mouse PCs. CAL-101 suppressed the TNF-α-induced TRPV2 expression in OGD/R-treated PCs, thus inhibiting the Ca 2+ uptake and PC contraction. Collectively, this study suggests that PI3Kδ is a critical regulator of PC function during ischemic stroke.
研究领域:
神经科学
·
药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH
·
2019
·
IF 2.929
Zhuoyu Wen,Yongjun Jiang,Linyuan Zhang,Xiaomeng Xu,Nan Zhao,Xiaohui Xu,Fang Wang,Jie Gao,Guo-Yuan Yang,Xinfeng Liu
Background Previous studies have estimated that the risk of recurrent stroke was nearly 20% shortly after a transient ischemic attack (TIA) or minor stroke. A missing or hypoplastic (<0.5 mm) anterior communicating artery can have deleterious effects on the brain. Our study aimed to investigate the effect of anterior communicating artery flow on neurovascular injury and neurobehavioral outcomes in mice with recurrent stroke and to identify its underlying mechanisms. Methods A recurrent stroke model was established by an initial cortical infarction followed by a corticostriatal infarction 3 days later. The vascular structure was visualized using synchrotron radiation angiography & magnetic resonance angiography in vivo and transparent endovascular perfusion imaging in vitro . Microvessel perfusion was assessed via fluorescein isothiocyanate perfusion. The infarct volume was measured by magnetic resonance imaging. Results The finding that anterior communicating artery flow facilitates pial artery patency in the ipsilateral hemisphere in mice with recurrent stroke suggests that compensatory collateral patency contributes to increased regional cerebral blood flow, enhanced microcirculatory perfusion, improved neurological function and reduced infarct volume. Conclusions The results of this study demonstrate that anterior communicating artery flow alleviates recurrent stroke-induced neurovascular injury and improves neurobehavioral outcomes by promoting the establishment of collateral circulation.
研究领域:
神经科学
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实验性中风研究
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脑血管疾病
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神经影像学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
·
2024
·
IF 4.9
Peng Zhang,Dan Yuan,Chenglei Luo,Wenjing Guo,Fengxian Li
Cerebral perfusion is functionally regulated by neural mechanisms in addition to the systemic hemodynamic variation, vascular reactivity and cerebral metabolism. Although anesthesia is generally esteemed to suppress the overall brain neural activity and metabolism, a few inhalation anesthetics, such as isoflurane, can increase cerebral perfusion, thus heightening the risks of higher intracranial pressure, bleeding, and brain edema during surgery. With the aid of laser speckle contrast imaging, we observed a transient yet limited effect of cerebral perfusion enhancement in mice from awake to anesthetized conditions with different concentration of isoflurane. Retrograde and antegrade tracing revealed a higher proportion of parasympathetic control more than sympathetic innervation for the blood vessels. Surprisingly, isoflurane directly activated pterygopalatine ganglion (PPG) explants and induced FOS expression in the cholinergic neurons. Chemogenetic activation of cholinergic PPG neurons reduced isoflurane-related cerebral perfusion. On the contrary, ablation of the cholinergic PPG neurons resulted in further enhancement of cerebral perfusion induced by isoflurane. While blocking muscarinic cholinergic receptors resulted in the overall reduction upon isoflurane stimulation, the blockage of nicotinic cholinergic receptors enhanced the isoflurane-induced cerebral perfusion only when PPG neurons exist. Collectively, these results suggest that PPG play important roles in regulating cerebral perfusion under isoflurane inhalation.
研究领域:
神经科学
·
麻醉学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2022
·
IF 10.334
Jiale Zhu,Zhiwei Jin,Lei Yang,Caili Zhao,Jianping Hu,Jinhu Chen,Yubao Han,Pei Yu,Jun Luo,Lingyi Kong,Chao Zhang
Promoting angiogenesis in the ischemic penumbra is a well-established method of ischemic stroke treatment. Ginkgolide B (GB) has long been recognized for its neuroprotective properties following stroke. As previously reported, it appears that stroke-induced neurogenesis and angiogenesis interact or are dependent on one another. Although the pharmacodynamic effect of GB on cerebral blood flow (CBF) following ischemic stroke has been reported, the molecular mechanism underlying this effect remains unknown. As such, this study sought to elucidate the pharmacodynamic effects and underlying mechanisms of GB on post-stroke angiogenesis. To begin, GB significantly increased the proliferation, migration, and tube formation capacity of mouse cerebral hemangioendothelioma cells (b.End3) and human umbilical vein endothelial cells (HUVEC). Additionally, GB significantly improved angiogenesis after oxygen-glucose deprivation/reperfusion (OGD/R) in endothelial cells. The dynamics of CBF, brain microvascular neovascularization and reconstruction, and brain endothelial tissue integrity were examined in middle cerebral artery occlusion (MCAO) mice following GB administration. Through label-free target detection techniques, we discovered for the first time that GB can specifically target Creatine Kinase B (CKB) and inhibit its enzymatic activity. Additionally, we demonstrated through network pharmacology and a series of molecular biology experiments that GB inhibited CKB and then promoted angiogenesis via the CCT/TRiC-SK1 axis. These findings shed new light on novel therapeutic strategies for neurological recovery and endothelial repair following ischemic stroke using GB therapy.
研究领域:
神经学
·
药理学
·
分子生物学
·
细胞生物学
·
卒中研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2023
·
IF 3.4
Bike Zhang,Dan Su,Yonggui Song,Huizhen Li,Changlian Chen,Liangliang Liao,Hongjie Zhang,Jian Luo,Ming Yang,Genhua Zhu,Zhifu Ai
Phytochemical investigation of the volatile oil of Yueju (YJVO) and its constituent herbs induced the detection of 52 compounds in YJVO, mainly monoterpenes and sesquiterpenes as well as a small amount of aromatic and aliphatic compounds. 5 of these compounds were found only in the YJVO instead of the volatile oil of its constituent herbs. The anti-depressant effect of YJVO was proved by behavioral tests in chronic unpredictable mild stress (CUMS) mice. An acute oral toxicity evaluation determined the LD 50 of YJVO was 5.780 mL/kg. Doppler ultrasound and laser speckle imaging have detected that the YJVO could improve depression-related cerebral blood flow. In addition, related neurotransmitters and proteins were analyzed through targeted metabolomics and immunofluorescence. The potential antidepressant mechanisms of YJVO related to significantly decreasing Glu in CUMS mice by up-regulating the ERK/AKT-mediated expression of GLT-1.
研究领域:
药理学
·
神经科学
·
植物化学
·
行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Yulong Chen,Qingzhou Cheng,Shan Zeng,Site Lv
Background: Migraine is a common neurovascular disorder with typical throbbing and unilateral headaches, causing a considerable healthcare burden on the global economy. This research aims to prepare chitosan-alginate (CS-AL) nanoparticles (NPs) containing Foshousan oil (FSSO) and investigate its potential therapeutic effects on the treatment of migraine. Methods: FSSO-loaded CS-AL NPs were prepared by using the single emulsion solvent evaporation method. Lipopolysaccharide (LPS)-stimulated BV-2 cells and nitroglycerin (NTG)-induced migraine mice were further used to explore anti-migraine activities and potential mechanisms of this botanical drug. Results: FSSO-loaded CS-AL NPs (212.1 ± 5.2 nm, 45.1 ± 6.2 mV) had a well-defined spherical shape with prolonged drug release and good storage within 4 weeks. FSSO and FSSO-loaded CS-AL NPs (5, 10, and 15 μg/mL) showed anti-inflammatory activities in LPS-treated BV-2 cells via reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO), but elevating interleukin-10 (IL-10) expressions. Moreover, FSSO-loaded CS-AL NPs (52 and 104 mg/kg) raised pain thresholds against the hot stimulus and decreased acetic acid-induced writhing frequency and foot-licking duration in NTG-induced migraine mice. Compared with the model group, calcitonin gene-related peptide (CGRP) and NO levels were downregulated, but 5-hydroxytryptamine (5-HT) and endothelin (ET) levels were upregulated along with rebalanced ET/NO ratio, and vasomotor dysfunction was alleviated by promoting cerebral blood flow (CBF) in the FSSO-loaded CS-AL NPs (104 mg/kg) group. Conclusion: FSSO-loaded CS-AL NPs could attenuate migraine via inhibiting neuroinflammation in LPS-stimulated BV-2 cells and regulating vasoactive substances in NTG-induced migraine mice. These findings suggest that the FSS formula may be exploited as new phytotherapy for treating migraine.
研究领域:
药理学
·
纳米技术
·
神经科学
·
植物药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOFACTORS
·
2023
·
IF 6
Zichen Gui,Jiawen Wang,Yue Zhang,Binbin Wan,Zhiqiang Ke,Zhanhong Ren,Xiaosong Yang,Min Lei,Xiying Guo,Xiufen Liu,Changhan Ouyang,Ninghua Wu,Qingjie Chen
Cognitive impairment is increasingly recognized as an important comorbidity of diabetes progression; however, the underlying molecular mechanism is unclear. Dapagliflozin, an inhibitor of sodium-glucose co-transporter 2 (SGLT2), has shown promising effects against diabetes in rodent experiments and human clinical assays. This study aimed to determine the underlying mechanism and examine the effect of dapagliflozin on diabetic cognitive impairment. To create an in vivo model of diabetic cognitive impairment, streptozotocin (STZ)-induced diabetic mice were used. Dapagliflozin was administered to mice for 8 weeks. The context fear condition and Morris water maze test was used to evaluate mice's behavioral change. Western blotting was used to evaluate protein expression. Hematoxylin and eosin (HE) and Nissl staining were applied to monitor morphological and structural changes. Congo red staining was performed to identify the formation of senile plaques. Mitochondria morphology was examined using a transmission electron microscope, and blood flow in the mouse cerebral cortex was measured using a laser Doppler imaging assay. Comparison to the diabetes mellitus (DM) group, the dapagliflozin group had lower glucose levels. Behavioral studies have shown that dapagliflozin can restore memory deficits in diabetic mice. The murky cell membrane edges and Nissl bodies more difficult to identify in the DM group were revealed by HE and Nissl staining, which were both improved by dapagliflozin treatment. Dapagliflozin inhibited the progression of Aβ generation and the reduced cerebral blood flow in the DM group was rescued. After dapagliflozin treatment, damaged mitochondria and lack of SGLT2 in the hippocampus and cortex of diabetic mice were repaired. Diabetes-induced cognitive dysfunction was attenuated by dapagliflozin and the effect was indirect rather than direct.
研究领域:
药理学
·
神经科学
·
糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2023
·Vol. 15
·期 27
·11625-11646
·
IF 6.7
Kai Wang,Wentao Zhou,Xiangyu Jin,Xuwei Shang,Xiaomei Wu,Lijuan Wen,Sufen Li,Yiling Hong,Jia Ke,Yichong Xu,Hong Yuan,Fuqiang Hu
Ischemic stroke is characterized by high morbidity, disability, and mortality. Unfortunately, the only FDA-approved pharmacological thrombolytic, alteplase, has a narrow therapeutic window of only 4.5 h. Other drugs like neuroprotective agents have not been clinically used because of their low efficacy. To improve the efficacy of neuroprotective agents and the effectiveness of rescue therapies for hyperacute ischemic stroke, we investigated and verified the variation trends of the blood–brain barrier (BBB) permeability and regional cerebral blood flow over 24 h in rats that had ischemic strokes. Hypoperfusion and the biphasic increase of BBB permeability are still the main limiting factors for lesion-specific drug distribution and drug brain penetration. Herein, the nitric oxide donor hydroxyurea (HYD) was reported to downregulate the expression of tight junction proteins and upregulate intracellular nitric oxide content in the brain microvascular endothelial cells subjected to oxygen–glucose deprivation, which was shown to facilitate the transport of liposomes across brain endothelial monolayer in an in vitro model. HYD also increased the BBB permeability and promoted microcirculation in the hyperacute phase of stroke. The neutrophil-like cell-membrane-fusogenic hypoxia-sensitive liposomes exhibited excellent performance in targeting the inflamed brain microvascular endothelial cells, enhancing cell association, and promoting rapid hypoxic-responsive release in the hypoxic microenvironment. Overall, the combined HYD and hypoxia-sensitive liposome dosing regimen effectively decreased the cerebral infarction volume and relieved neurological dysfunction in rats that had ischemic strokes; these therapies were involved in the anti-oxidative stress effect and the neurotrophic effect mediated by macrophage migration inhibitory factor.
研究领域:
神经科学
·
药理学
·
治疗学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Yonggui Song,Meixizi Lai,Zhou Liao,Zhentao Zhang,Genhua Zhu,Ming Yang,Zhifu Ai,Qin Zheng,Dan Su
Background Since the pathogenesis of depression is complex, antidepressant therapy remains unsatisfactory. Recent evidence suggests a link between depression and lipid metabolism. Saikosaponin (SS) exhibits antidepression and lipid-regulating effects in modern pharmacology. However, it is unknown whether lipid regulation is the key mechanism of the SS antidepressant effect and how it works. Purpose In this study, we investigated the relationship between the antidepressant activity of SS and the regulation of lipid metabolism and explored potential mechanisms. Methods APOE -/- mice, in combination with the chronic unpredictable mild stress (CUMS) model, were used to study the relationship between SS antidepressant activity and lipid metabolism through behavioral, electrophysiological techniques, and non-targeted lipidomics. Western blot, primary cell culture technology, and laser speckle cerebral blood flow imaging were employed to elucidate potential mechanisms. GraphPad Prism was used for statistical analysis, and p < 0.05 was considered statistically significant. Results APOE -/- mice exhibit more severe depressive-like behavior and dysregulation of sphingolipid metabolism in CUMS. SS alleviates depressive behavior and cortical sphingolipid metabolism disorder caused by CUMS, but has no effect on APOE -/- mice. SS alleviates the imbalance between ceramide (Cer) and sphingomyelin (SM) through acidic sphingomyelinase (AMSase). In addition, SS regulates neuronal glutamate release via sphingolipid metabolism, thereby alleviating the CUMS-induced inhibition of neurovascular coupling (regulates metabotropic glutamate receptor and IP3 receptor), which ameliorates the reduction of cerebral blood flow in depressed mice. Conclusion Our study highlights the role of lipid metabolism in the antidepressant activity of SS and explores its underlying mechanisms. This study provided new insights into the better understanding of the antidepressant mechanisms of phytomedicine while increasing the possibility of lipid metabolism as a therapeutic strategy for depression.
研究领域:
药理学
·
神经科学
·
脂质生物学
·
行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）