Journal of Cerebral Blood Flow & Metabolism最新文献_第5页

Hyaluronidase reduced edema after experimental traumatic brain injury 透明质酸酶减轻实验性创伤性脑损伤后水肿

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2020-10-01 DOI: 10.1177/0271678X19882780

Patricia M. Washington, Changhee Lee, M. K. Dwyer, E. Konofagou, S. Kernie, B. Morrison

{"title":"Hyaluronidase reduced edema after experimental traumatic brain injury","authors":"Patricia M. Washington, Changhee Lee, M. K. Dwyer, E. Konofagou, S. Kernie, B. Morrison","doi":"10.1177/0271678X19882780","DOIUrl":"https://doi.org/10.1177/0271678X19882780","url":null,"abstract":"Cerebral edema and the subsequent increased intracranial pressure are associated with mortality and poor outcome following traumatic brain injury. Previous in vitro studies have shown that the Gibbs-Donnan effect, which describes the tendency of a porous, negatively charged matrix to attract positive ions and water, applies to brain tissue and that enzymatic reduction of the fixed charge density can prevent tissue swelling. We tested whether hyaluronidase, an enzyme that degrades the large, negatively charged glycosaminoglycan hyaluronan, could reduce brain edema after traumatic brain injury. In vivo, intracerebroventricular injection of hyaluronidase after controlled cortical impact in mice reduced edema in the ipsilateral hippocampus at 24 h by both the wet-weight/dry-weight method (78.15 ± 0.65% vs. 80.4 ± 0.46%; p < 0.01) and T2-weighted magnetic resonance imaging (13.88 ± 3.09% vs. 29.23 ± 6.14%; p < 0.01). Hyaluronidase did not adversely affect blood–brain-barrier-integrity measured by dynamic contrast-enhanced magnetic resonance imaging, nor did hyaluronidase negatively affect functional recovery after controlled cortical impact measured with the rotarod or Morris water maze tasks. Reduction of fixed charge density by hyaluronidase was confirmed in cortical explants in vitro (5.46 ± 1.15 µg/mg vs. 7.76 ± 1.87 µg/mg; p < 0.05). These data demonstrate that targeting the fixed charge density with hyaluronidase reduced edema in an in vivo mouse model of traumatic brain injury.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"25 3-4","pages":"2026 - 2037"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72627745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Measurement of CMRO2 and its relationship with CBF in hypoxia with an extended calibrated BOLD method 用扩展的校准BOLD方法测量缺氧时cro2及其与CBF的关系

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2020-10-01 DOI: 10.1177/0271678X19885124

Yaoyu Zhang, Yayan Yin, Huanjie Li, Jia-Hong Gao

{"title":"Measurement of CMRO2 and its relationship with CBF in hypoxia with an extended calibrated BOLD method","authors":"Yaoyu Zhang, Yayan Yin, Huanjie Li, Jia-Hong Gao","doi":"10.1177/0271678X19885124","DOIUrl":"https://doi.org/10.1177/0271678X19885124","url":null,"abstract":"Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) are physiological parameters that not only reflect brain health and disease but also jointly contribute to blood oxygen level-dependent (BOLD) signals. Nevertheless, unsolved issues remain concerning the CBF–CMRO2 relationship in the working brain under various oxygen conditions. In particular, the CMRO2 responses to functional tasks in hypoxia are less studied. We extended the calibrated BOLD model to incorporate CMRO2 measurements in hypoxia. The extended model, which was cross-validated with a multicompartment BOLD model, considers the influences of the reduced arterial saturation level and increased baseline cerebral blood volume (CBV) and deoxyhemoglobin concentration on the changes of BOLD signals in hypoxia. By implementing a pulse sequence to simultaneously acquire the CBV-, CBF- and BOLD-weighted signals, we investigated the effects of mild hypoxia on the CBF and CMRO2 responses to graded visual stimuli. Compared with normoxia, mild hypoxia caused significant alterations in both the amplitude and the trend of the CMRO2 responses but did not impact the corresponding CBF responses. Our observations suggested that the flow-metabolism coupling strategies in the brain during mild hypoxia were different from those during normoxia.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"38 1","pages":"2066 - 2080"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79842963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Early-stage 11C-Flumazenil PET predicts day-14 selective neuronal loss in a rodent model of transient focal cerebral ischemia 早期11c -氟马西尼PET预测鼠类短暂局灶性脑缺血模型第14天选择性神经元损失

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2020-10-01 DOI: 10.1177/0271678X19883040

J. Hughes, J. Beech, P. Jones, Dechao Wang, D. Menon, F. Aigbirhio, T. Fryer, J. Baron

{"title":"Early-stage 11C-Flumazenil PET predicts day-14 selective neuronal loss in a rodent model of transient focal cerebral ischemia","authors":"J. Hughes, J. Beech, P. Jones, Dechao Wang, D. Menon, F. Aigbirhio, T. Fryer, J. Baron","doi":"10.1177/0271678X19883040","DOIUrl":"https://doi.org/10.1177/0271678X19883040","url":null,"abstract":"Predicting tissue outcome early after stroke is an important goal. MRI >3 h accurately predicts infarction but is insensitive to selective neuronal loss (SNL). Previous studies suggest that chronic-stage 11 C-flumazenil PET (FMZ-PET) is a validated marker of SNL in rats, while early-stage FMZ-PET may predict infarction. Whether early FMZ-PET also predicts SNL is unknown. Following 45-min distal MCA occlusion, adult rats underwent FMZ-PET at 1 h and 48 h post-reperfusion to map distribution volume (VT), which reflects GABA-A receptor binding. NeuN immunohistochemistry was performed at Day 14. In each rat, VT and %NeuN loss were determined in 44 ROIs spanning the hemisphere. NeuN revealed isolated SNL and cortical infarction in five and one rats, respectively. In the SNL subgroup, VT-1 h was mildly reduced and only weakly predicted SNL, while VT-48 h was significantly increased and predicted SNL both individually (p < 0.01, Kendall) and across the group (p < 0.001), i.e. the higher the VT, the stronger the SNL. Similar correlations were found in the rat with infarction. Our findings suggest GABA-A receptors are still present on injured neurons at the 48 h timepoint, and the increased 48 h VT observed here is consistent with earlier rat studies showing early GABA-A receptor upregulation. That FMZ binding at 48 h was predictive of SNL may have clinical implications.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"40 1","pages":"1997 - 2009"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86877839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Vasodilator effects of sulforaphane in cerebral circulation: A critical role of endogenously produced hydrogen sulfide and arteriolar smooth muscle KATP and BK channels in the brain 萝卜硫素在脑循环中的血管舒张作用:内源性硫化氢和脑动脉平滑肌KATP和BK通道的关键作用

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2020-10-01 DOI: 10.1177/0271678X19878284

H. Parfenova, Jianxiong Liu, Daniel T Hoover, A. Fedinec

{"title":"Vasodilator effects of sulforaphane in cerebral circulation: A critical role of endogenously produced hydrogen sulfide and arteriolar smooth muscle KATP and BK channels in the brain","authors":"H. Parfenova, Jianxiong Liu, Daniel T Hoover, A. Fedinec","doi":"10.1177/0271678X19878284","DOIUrl":"https://doi.org/10.1177/0271678X19878284","url":null,"abstract":"We investigated the effects of sulforaphane (SFN), an isothiocyanate from cruciferous vegetables, in the regulation of cerebral blood flow using cranial windows in newborn pigs. SFN administered topically (10 µM–1 mM) or systemically (0.4 mg/kg ip) caused immediate and sustained dilation of pial arterioles concomitantly with elevated H2S in periarachnoid cortical cerebrospinal fluid. H2S is a potent vasodilator of cerebral arterioles. SFN is not a H2S donor but it acts via stimulating H2S generation in the brain catalyzed by cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS). CSE/CBS inhibitors propargylglycine, β-cyano-L-alanine, and aminooxyacetic acid blocked brain H2S generation and cerebral vasodilation caused by SFN. The SFN-elicited vasodilation requires activation of potassium channels in cerebral arterioles. The inhibitors of KATP and BK channels glibenclamide, paxilline, and iberiotoxin blocked the vasodilator effects of topical and systemic SFN, supporting the concept that H2S is the mediator of the vasodilator properties of SFN in cerebral circulation. Overall, we provide first evidence that SFN is a brain permeable compound that increases cerebral blood flow via a non-genomic mechanism that is mediated via activation of CSE/CBS-catalyzed H2S formation in neurovascular cells followed by H2S-induced activation of KATP and BK channels in arteriolar smooth muscle.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"54 1","pages":"1987 - 1996"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81488329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

Assessment of a white matter reference region for 11C-UCB-J PET quantification 11C-UCB-J PET定量白质参考区评估

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2020-09-01 DOI: 10.1177/0271678X19879230

Samantha Rossano, T. Toyonaga, S. Finnema, M. Naganawa, Yihuan Lu, N. Nabulsi, J. Ropchan, S. De Bruyn, C. Otoul, A. Stockis, J. Nicolas, Paul Martin, J. Mercier, Yiyun Huang, R. P. Maguire, R. Carson

{"title":"Assessment of a white matter reference region for 11C-UCB-J PET quantification","authors":"Samantha Rossano, T. Toyonaga, S. Finnema, M. Naganawa, Yihuan Lu, N. Nabulsi, J. Ropchan, S. De Bruyn, C. Otoul, A. Stockis, J. Nicolas, Paul Martin, J. Mercier, Yiyun Huang, R. P. Maguire, R. Carson","doi":"10.1177/0271678X19879230","DOIUrl":"https://doi.org/10.1177/0271678X19879230","url":null,"abstract":"11C-UCB-J is a positron emission tomography (PET) radioligand that has been used in humans for synaptic vesicle glycoprotein 2A (SV2A) imaging and as a potential synaptic density marker. The centrum semiovale (CS) is a proposed reference region for noninvasive quantification of 11C-UCB-J, due to negligible concentrations of SV2A in this region in baboon brain assessed by in vitro methods. However, in displacement scans with SV2A-specific drug levetiracetam in humans, a decrease in 11C-UCB-J concentration was observed in the CS, consistent with some degree of specific binding. The current study aims to validate the CS as a reference region by (1) optimizing CS region of interest (ROI) to minimize spill-in from gray matter with high radioactivity concentrations; (2) investigating convergence of CS ROI values using ordered subset expectation maximization (OS-EM) reconstruction, and (3) comparing baseline CS volume of distribution (VT) to nondisplaceable uptake in gray matter, VND. Improving ROI definition and increasing OS-EM iterations during reconstruction decreased the difference between CS VT and VND. However, even with these corrections, CS VT overestimated VND by ∼35–40%. These measures showed significant correlation, suggesting that, though biased, the CS may be a useful estimate of nondisplaceable uptake, allowing for noninvasive quantification for SV2A PET.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"26 1","pages":"1890 - 1901"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87135018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 74

High long-term test–retest reliability for extrastriatal 11C-raclopride binding in healthy older adults 健康老年人肠外11C-raclopride结合的长期重测信度高

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2020-09-01 DOI: 10.1177/0271678X19874770

Nina Karalija, Lars Jonassson, J. Johansson, G. Papenberg, Alireza Salami, M. Andersson, K. Riklund, L. Nyberg, C. Boraxbekk

{"title":"High long-term test–retest reliability for extrastriatal 11C-raclopride binding in healthy older adults","authors":"Nina Karalija, Lars Jonassson, J. Johansson, G. Papenberg, Alireza Salami, M. Andersson, K. Riklund, L. Nyberg, C. Boraxbekk","doi":"10.1177/0271678X19874770","DOIUrl":"https://doi.org/10.1177/0271678X19874770","url":null,"abstract":"In vivo dopamine D2-receptor availability is frequently assessed with 11C-raclopride and positron emission tomography. Due to low signal-to-noise ratios for 11C-raclopride in areas with low D2 receptor densities, the ligand has been considered unreliable for measurements outside the dopamine-dense striatum. Intriguingly, recent studies show that extrastriatal 11C-raclopride binding potential (BPND) values are (i) reliably higher than in the cerebellum (where D2-receptor levels are negligible), (ii) correlate with behavior in the expected direction, and (iii) showed good test–retest reliability in a sample of younger adults. The present work demonstrates high seven-month test–retest reliability of striatal and extrastriatal 11C-raclopride BPND values in healthy, older adults (n = 27, age: 64–78 years). Mean 11C-raclopride BPND values were stable between test sessions in subcortical nuclei, and in frontal and temporal cortices (p > 0.05). Across all structures analyzed, intraclass correlation coefficients were high (0.85–0.96), absolute variability was low (mean: 4–8%), and coefficients of variance ranged between 9 and 25%. Furthermore, regional 11C-raclopride BPND values correlated with previously determined 18F-fallypride BPND values (ρ = 0.97 and 0.92 in correlations with and without striatal values, respectively, p < 0.01) and postmortem determined D2-receptor densities (including striatum: ρ = 0.92; p < 0.001; excluding striatum: ρ = 0.75; p = 0.067). These observations suggest that extrastriatal 11C-raclopride measurements represent a true D2 signal.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"27 1","pages":"1859 - 1868"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78833673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Normalization of reduced functional connectivity after revascularization of asymptomatic carotid stenosis 无症状颈动脉狭窄血运重建术后功能连通性降低的正常化

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2020-09-01 DOI: 10.1177/0271678X19874338

F. Quandt, F. Fischer, Julian Schröder, Marlene Heinze, S. Kessner, C. Malherbe, R. Schulz, B. Cheng, J. Fiehler, C. Gerloff, G. Thomalla

{"title":"Normalization of reduced functional connectivity after revascularization of asymptomatic carotid stenosis","authors":"F. Quandt, F. Fischer, Julian Schröder, Marlene Heinze, S. Kessner, C. Malherbe, R. Schulz, B. Cheng, J. Fiehler, C. Gerloff, G. Thomalla","doi":"10.1177/0271678X19874338","DOIUrl":"https://doi.org/10.1177/0271678X19874338","url":null,"abstract":"Internal carotid artery stenosis is a risk factor for ischemic stroke. Even in the absence of visible structural brain changes, patients with asymptomatic stenosis are prone to cognitive impairment. On a neuronal level, it was suggested that stenosis may lead to disturbed functional brain connectivity. If so, carotid revascularization should have an effect on hypothesized brain network disturbances. We studied functional connectivity in a motor network by resting-state electroencephalography in 12 patients with high grade asymptomatic carotid stenosis before and after interventional or surgical revascularization as compared to 23 controls. In patients with stenosis, functional connectivity of neural oscillations was significantly decreased prior and improved returning to normal connectivity after revascularization. In a subgroup of patients, also studied by contrast perfusion magnetic resonance imaging, reduced connectivity was associated with decreased regional brain perfusion reflected by increased mean transit time in the middle cerebral artery borderzone. Cognitive testing revealed only minor differences between patients and controls. In summary, we identified oscillatory connectivity changes in patients with asymptomatic carotid stenosis correlating with regional hypoperfusion, which both normalized after revascularization. Hence, electrophysiological changes might be a reversible precursor preceding macroscopic structural brain damage and behavioral impairment in patients with asymptomatic carotid stenosis.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"3 1","pages":"1838 - 1848"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80860139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Role of deep medullary veins in pathogenesis of lacunes: Longitudinal observations from the CIRCLE study 深髓静脉在肾陷窝发病机制中的作用:来自CIRCLE研究的纵向观察

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2020-09-01 DOI: 10.1177/0271678X19882918

Ying Zhou, Qingqing Li, Ruiting Zhang, Wenhua Zhang, Shenqiang Yan, Jinjin Xu, Shuyue Wang, Minming Zhang, M. Lou

{"title":"Role of deep medullary veins in pathogenesis of lacunes: Longitudinal observations from the CIRCLE study","authors":"Ying Zhou, Qingqing Li, Ruiting Zhang, Wenhua Zhang, Shenqiang Yan, Jinjin Xu, Shuyue Wang, Minming Zhang, M. Lou","doi":"10.1177/0271678X19882918","DOIUrl":"https://doi.org/10.1177/0271678X19882918","url":null,"abstract":"Our purpose is to assess the role of deep medullary veins in pathogenesis of lacunes in patients with cerebral small vessel disease (cSVD). We included patients with baseline and 2.5-year follow-up MRI in CIRCLE study. Susceptibility Weighted Imaging-Phase images were used to evaluate deep medullary veins based on a brain region-based visual score, and T2-Fluid-Attenuated-Inversion-Recovery images were used to evaluate lacunes. Cerebral blood flow and microstructural parameters in white matter hyperintensities and normal appearing white matter were also analyzed. A total of 203 cSVD patients were analyzed and 101 (49.8%) patients had baseline lacunes. Among them, 64 patients had follow-up MRI, including 16 (25.0%) with new lacunes. The patients’ deep medullary veins median score was 9 (7–12). At baseline, high deep medullary veins score was independently associated with the presence of lacunes after adjusting for age, diabetes mellitus, white matter hyperintensities volume and cerebral blood flow or white matter microstructural parameters (all p < 0.001). Longitudinally, high deep medullary veins score was independently associated with new lacunes after adjusting for gender (p < 0.001). The association was also independent of white matter hyperintensities volumes, cerebral blood flow or white matter microstructural parameters (all p < 0.05). Our results suggest that deep medullary veins disruption might be involved in pathogenesis of lacunes.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"52 1","pages":"1797 - 1805"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81861286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Integrin α5β1 inhibition by ATN-161 reduces neuroinflammation and is neuroprotective in ischemic stroke ATN-161抑制整合素α5β1可减轻缺血性脑卒中的神经炎症并具有神经保护作用

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2020-08-01 DOI: 10.1177/0271678X19880161

Danielle N. Edwards, K. Salmeron, D. Lukins, A. Trout, J. Fraser, G. Bix

{"title":"Integrin α5β1 inhibition by ATN-161 reduces neuroinflammation and is neuroprotective in ischemic stroke","authors":"Danielle N. Edwards, K. Salmeron, D. Lukins, A. Trout, J. Fraser, G. Bix","doi":"10.1177/0271678X19880161","DOIUrl":"https://doi.org/10.1177/0271678X19880161","url":null,"abstract":"Stroke remains a leading cause of death and disability with limited therapeutic options. Endothelial cell β1 integrin receptors play a direct role in blood-brain barrier (BBB) dysfunction through regulation of tight junction proteins and infiltrating leukocytes, potentially mediated by β1 integrins. Following tandem transient common carotid artery/middle cerebral artery occlusion on wild-type mice, we administered the integrin a5b1 inhibitor, ATN-161, intraperitoneal (IP) injection at 1 mg/kg acutely after reperfusion, on post-stroke day (PSD)1 and PSD2. Systemic changes (heart rate, pulse distension, and body temperature) were determined. Additionally, infarct volume and edema were determined by 2,3-triphenyltetrazolium chloride and magnetic resonance imaging, while neurological changes were evaluated using an 11-point Neuroscore. Brain immunohistochemistry was performed for claudin-5, α5β1, IgG, and CD45 + cells, and quantitative polymerase chain reaction (qPCR) was performed for matrix metalloproteinase-9 (MMP-9), interleukin (IL)-1β, collagen IV, and CXCL12. ATN-161 significantly reduced integrin α5β1 expression in the surrounding peri-infarct region with no systemic changes. Infarct volume, edema, and functional deficit were significantly reduced in ATN-161-treated mice. Furthermore, ATN-161 treatment reduced IgG extravasation into the parenchyma through conserved claudin-5, collagen IV, CXCL12 while reducing MMP-9 transcription. Additionally, IL-1β and CD45 + cells were reduced in the ipsilateral cortex following ATN-161 administration. Collectively, ATN-161 may be a promising novel stroke therapy by reducing post-stroke inflammation and BBB permeability.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"144 1","pages":"1695 - 1708"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77514856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 23

Choroid plexus perfusion and intracranial cerebrospinal fluid changes after angiogenesis 血管生成后脉络膜丛灌注及颅内脑脊液变化

Journal of Cerebral Blood Flow & Metabolism Pub Date : 2020-08-01 DOI: 10.1177/0271678X19872563

Skylar E Johnson, C. McKnight, Sarah K. Lants, Meher R. Juttukonda, M. Fusco, R. Chitale, Paula C Donahue, D. Claassen, M. Donahue

{"title":"Choroid plexus perfusion and intracranial cerebrospinal fluid changes after angiogenesis","authors":"Skylar E Johnson, C. McKnight, Sarah K. Lants, Meher R. Juttukonda, M. Fusco, R. Chitale, Paula C Donahue, D. Claassen, M. Donahue","doi":"10.1177/0271678X19872563","DOIUrl":"https://doi.org/10.1177/0271678X19872563","url":null,"abstract":"Recent studies have provided evidence that cortical brain ischemia may influence choroid plexus function, and such communication may be mediated by either traditional CSF circulation pathways and/or a possible glymphatic pathway. Here we investigated the hypothesis that improvements in arterial health following neoangiogenesis alter (i) intracranial CSF volume and (ii) choroid plexus perfusion in humans. CSF and tissue volume measurements were obtained from T1-weighted MRI, and cortical and choroid plexus perfusion were obtained from perfusion-weighted arterial spin labeling MRI, in patients with non-atherosclerotic intracranial stenosis (e.g. Moyamoya). Measurements were repeated after indirect surgical revascularization, which elicits cortical neoangiogenesis near the revascularization site (n = 23; age = 41.8 ± 13.4 years), or in a cohort of participants at two time points without interval surgeries (n = 10; age = 41.7 ± 10.7 years). Regression analyses were used to evaluate dependence of perfusion and volume on state (time 1 vs. 2). Post-surgery, neither CSF nor tissue volumes changed significantly. In surgical patients, cortical perfusion increased and choroid plexus perfusion decreased after surgery; in participants without surgeries, cortical perfusion reduced and choroid plexus perfusion increased between time points. Findings are discussed in the context of a homeostatic mechanism, whereby arterial health, paravascular flow, and/or ischemia can affect choroid plexus perfusion.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"1 1","pages":"1658 - 1671"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76288809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12